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Prognosis and treatment of patients with acute alcoholic hepatitis.
Despite alcoholic hepatitis (AH) is the most acute manifestation of alcohol-related liver disease, its treatment remains controversial. Corticosteroids, given either as monotherapy or together with N-acetylecysteine, have been associated with a moderate short-term survival benefit in patients with severe disease. The Maddrey's discriminant function; Glasgow alcoholic hepatitis score; age, bilirubin, INR and creatinine score; and the Model for end-stage liver disease have been proposed for stratifying prognosis in AH enabling selection of the patients to treat. Definition of treatment non-responders using the Lille model after 7 days of therapy may prevent a detrimental impact of prolonged corticosteroids. Pentoxifylline is an effective alternative reducing the occurrence of hepatorenal syndrome. Emerging evidence supports use of liver transplantation in a strictly selected subset of corticosteroid non-responders. PMID:24716632
Papastergiou, Vassilios; Burroughs, Andrew K; Tsochatzis, Emmanuel A
Pentoxifylline Improves Short-term Survival in Severe Acute Alcoholic Hepatitis: A Double-Blind, Placebo-Controlled Trial
Background & Aims: An earlier pilot study from our liver unit suggested benefit from treatment with pentoxifylline (PTX), an inhibitor of tumor necrosis factor (TNF), in severe acute alcoholic hepatitis. The aim of the present study was to evaluate this treatment in a larger cohort of patients. Methods: One hundred one patients with severe alcoholic hepatitis (Maddrey discriminant factor ?
Evangelos Akriviadis; Ravi Botla; William Briggs; Steven Han; Telfer Reynolds; Obaid Shakil
Diagnosis and management of alcoholic hepatitis.
Alcoholic hepatitis is a form of severe, cholestatic liver disease that results from consumption of large amount of alcohol during a sustained period of time in a subset of alcoholics. Symptoms could be mild and nonspecific toĀmore severe. The diagnosis of alcoholic hepatitis can be made with a thorough history, physical examination, and review of laboratory results. Liver biopsy is confirmatory but generally not indicated for the diagnosis. Abstinence is the key form of therapeutic intervention. Despite variable results in clinical trials, corticosteroids and pentoxifylline seem to provide moderate survival benefit. Liver transplantation in acute alcoholic hepatitis is contentious. PMID:23101979
Sohail, Umair; Satapathy, Sanjaya K
A novel mortality model for acute alcoholic hepatitis including variables recorded after admission to hospital.
Severe forms of alcoholic hepatitis in patients with alcoholic liver disease are associated with high mortality; it is therefore vital to identify those patients at greatest risk of mortality in 28 days as they may benefit from aggressive intervention. The aim of this study is to propose a new predictive model that can be used in clinical practice to identify such patients and to monitor their progress while in hospital. A cohort of 82 patients was selected and for each of them, a number of clinical findings and standard laboratory tests at the time of admission to hospital were recorded. Also, some variables were collected up to 7 days after admission. The proposed logistic regression model selected four statistically significant predictors (namely, the level of creatinine on and after admission, the presence of encephalopathy and prothrombin time evaluated after admission). A comparison with the available mortality predictive scores showed an increase by 25% in predictive power, demonstrating increased accuracy in identifying these sick patients with alcoholic hepatitis in clinical practice. PMID:24377696
Mazzocco, Thomas; Hussain, Amir; Hussain, Sajid; Shah, Amir A
Management of alcoholic hepatitis: Current concepts
Alcoholic hepatitis is a devastating form of acute liver injury seen in chronic alcohol abusers with significant morbidity and mortality. It is a multisystem disease that is precipitated by ingesting large quantities of alcohol with genetic and environmental factors playing a role. Prognostic criteria have been developed to predict disease severity and these criteria can serve as indicators to initiate medical therapy. Primary therapy remains abstinence and supportive care, as continued alcohol abuse is the most important risk factor for disease progression. The cornerstone of supportive care remains aggressive nutritional support, and although acute alcoholic hepatitis has been extensively studied, few specific medical therapies have been successful. Corticosteroids remain the most effective medical therapy available in improving short term survival in a select group of patients with alcoholic hepatitis; however, the long-term outcome of drug therapies is still not entirely clear and further clinical investigation is necessary. While liver transplantation for acute alcoholic hepatitis have demonstrated promising results, this practice remains controversial and has not been advocated universally, with most transplant centers requiring a prolonged period of abstinence before considering transplantation. Extracorporeal liver support devices, although still experimental, have been developed as a form of liver support to give additional time for liver regeneration. These have the potential for a significant therapeutic option in the future for this unfortunately dreadful disease.
Karsan, Hetal A; Parekh, Samir
Acute Liver Injury in a Patient with Alcohol Dependence: A Case Resembling Autoimmune Hepatitis or Drug-Induced Liver Injury
Some patients with alcohol dependence may initially present with atypical laboratory and histological features resembling autoimmune hepatitis (AIH) or drug-induced liver injury (DILI). Even with liver biopsy, it may be difficult to diagnose certain patients with alcohol dependence. However, careful follow-up of our patient and consultations with the attending psychiatrist were successful in diagnosing alcohol dependence and its liver injury. The immune mechanisms of alcoholic liver diseases, AIH and DILI may be overlapping. Certain patients are suffering from AIH with flares on a background of alcohol abuse. Certain patients with alcohol abuse may have a past history of DILI. This might be consistent with the fact that alcohol dependence initially presents with atypical laboratory features of AIH or DILI. With careful observation, the clinician should remind himself that alcohol dependence is not always required for developing liver disease, since many patients with liver disease do not meet the criteria for alcohol dependence.
Hayashi, Masahiro; Kanda, Tatsuo; Nakamura, Masato; Miyamura, Tatsuo; Yasui, Shin; Nakamoto, Shingo; Wu, Shuang; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu
Acute alcohol intoxication is a clinically harmful condition that usually follows the ingestion of a large amount of alcohol. Clinical manifestations are heterogeneous and involve different organs and apparatuses, with behavioral, cardiac, gastrointestinal, pulmonary, neurological, and metabolic effects. The management of an intoxicated patient occurs mainly in the emergency department and is aimed at stabilizing the clinical condition of the patient, depending on his/her clinical presentation. One specific drug that is useful in the treatment of acute alcohol intoxication is metadoxine, which is able to accelerate ethanol excretion. In patients presenting an acute alcohol intoxication, alcohol-related disorders should be detected so that the patient can be directed to an alcohol treatment unit, where a personalized, specific treatment can be established. PMID:19046719
Vonghia, Luisa; Leggio, Lorenzo; Ferrulli, Anna; Bertini, Marco; Gasbarrini, Giovanni; Addolorato, Giovanni
The hepatic-arterial/portal-venous scintiangiogram in alcoholic hepatitis
This study was designed to identify abnormalities in the hepatic-arterial/portal-venous scintiangiogram (SA) in alcoholic hepatitis (AH). SA's were performed in 35 patients with acute alcoholic hepatitis (AAH), 8; acute alcoholic hepatitis superimposed on cirrhosis (A/C), 14; and cirrhosis (C), 13. Posterior flows were done with a bolus of 10 mCi Tc-99m sulfur colloid with computer time-activity curves over the liver and left kidney. Curves were analyzed for per cent of hepatic arterial (HA) and portal venous contribution using the slope ratio method. Hepatic arterialization was estimated from the angle of the HA component of the curve. Reversal of the relative contribution of the hepatic and portal components of total flow were seen in all groups. Although quite severe in AH, the degree of reversal could not be used to differentiate among the groups. The average HA angle in AAH was 48.3 +- 8.1, in A/C 41.5 +- 10.6, and in C 30.4 +- 12.1. In reviewing the data of only those in the acute clinical phase of AH and not the recovery phase (1 AAH, 3 A/C) and those without other causes of alteration in hepatic arterialization (1 hepatoma, 1 portalcaval shunt, 6 renal failure), the average HA angle in AAH was 50.1 +- 6.6, 45.4 +- 8.2 in A/C, and 23.2 +- 4.2 in C. In 6 with renal failure (2 C, 2AAH, 2 A/C) the HA angle ws 52.7 +- 5.7. In all cases cirrhosis could be differentiated from both A/C (P=.05) and AAH (P<.01) using the HA angle. In absence of renal failure, portal shunt, or hepatoma, P was <.01 in both comparisons.
Stewart, C.; Sakimura, I.; Siegel, M.E.; Harley, H.; Lee, K.
Hyperbilirubinaemia and haemolytic anaemia in acute alcoholic hepatitis: there's oil in them thar veins.
A Caucasian woman in her late 30s was evaluated after a period of binge drinking and found to have hyperbilirubinaemia for which she was referred for consideration of cholecystectomy. After exclusion of other possibilities, Zieve's syndrome was diagnosed. This is a condition of hyperbilirubinaemia, Coombs' negative haemolytic anaemia and hyperlipidaemia associated with alcoholism. Abstinence from alcohol remains the only known effective treatment, and appreciation of the entity can prevent unnecessary biliary procedures. The patient improved with supportive measures and was discharged in stable condition. PMID:24748143
Hashmi, Salman; Allison, Michael G; McCurdy, Michael T; Reed, Robert M
Pharmacokinetics of ornidazole in patients with acute viral hepatitis, alcoholic cirrhosis, and extrahepatic cholestasis.
Pharmacokinetics of ornidazole, a nitroimidazole derivative, was investigated after intravenous injection in 3 groups of 10 patients with different hepatic diseases: hepatitis, noncholestatic cirrhosis and extrahepatic cholestasis. Plasma concentrations of ornidazole and its two major hydroxylated metabolites, M1 [alpha-(chloromethyl)-2-hydroxymethyl-5-nitroimidazole-1-ethanol] and M4 [3-(2-methyl-5-nitroimidazole 1-yl)-1,2-propane diol] were measured by HPLC assay. As a consequence of a decreased clearance (26% to 48%), the half-life and MRT are increased in all patients by 19% to 38% when compared with healthy volunteers. No clear difference could be established between the different groups. The volume of distribution remains the same in all patients and controls except those suffering from cancer. As previously shown in patients with severe liver cirrhosis, both metabolites accumulate in plasma as a result of decreased elimination; formation is no longer the rate-limiting step of their kinetics. This metabolite accumulation is in part due to decreased biliary excretion and to hepatocellular failure. PMID:2702794
Taburet, A M; Attali, P; Bourget, P; Etienne, J P; Singlas, E
Optimal management of alcoholic hepatitis.
Alcoholic hepatitis, a clinical syndrome among people with chronic and active alcohol abuse presents with with jaundice and liver failure with or without hepatic encephalopathy. In patients with severe episode, this condition has a potential for 40-50% mortality within a month of presentation. Corticosteroids and pentoxifylline, only available current treatment options provide only about 50% survival benefit. Response to corticosteroids can only be assessed at 1 week of initiation of these drugs using Lille score or documentation of improvement in bilirubin levels. Requirement of minimum 6 months abstinence for liver transplantation cannot be met for alcoholic hepatitis patients who fail to respond to steroids. Emerging data on the benefit of liver transplantation for select patients with first episode of severe AH with non-response to steroids are encouraging. There remains an unmet need for studies assessing newer therapeutic targets and drugs and for optimizing the currently available treatment options. In this regard, decision to promote clinical and translational research by the National Institute of Alcohol Abuse and Alcoholism will be helpful in improving survival of patients with alcoholic hepatitis. PMID:24632766
Raff, E; Singal, A K
Alcoholic hepatitis: diagnosis and management in 2012.
Alcoholic hepatitis is a severe form of alcohol-related liver injury and one of the most frequent liver presentations seen by acute medical services. The condition typically affects young and middle-aged adults who present with jaundice and coagulopathy. Many patients fulfil the criteria for acute-on-chronic liver failure, though often the diagnosis of cirrhosis is only made after hospitalization. Despite over four decades of study, controversy surrounds many aspects of diagnosis and management, and short-term mortality in severe disease remains high. This review summarizes recent and important literature of relevance to clinicians, including aids to diagnosis, clinical prognostic scores and evidence for current medical therapies. Contentious issues such as the need for liver biopsy in diagnosis and the role for liver transplantation in those who fail to respond to medical treatment are also discussed. PMID:23237255
Potts, Jonathan R; Verma, Sumita
[Management of severe alcoholic hepatitis].
Severe alcoholic hepatitis is still associated with high mortality and presence of liver failure manifested by jaundice, coagulopathy and encephalopathy is a poor prognostic indicator. The management of these patients includes at first hand several supportive measures as treatment of alcohol withdrawal, administration of fluid and vitamins and admission to an intensive care unit in the unstable patient. Glucocorticoids have been since decades the most intensively studied therapy in alcoholic hepatitis and are effective in certain subgroups. Indication for such a therapy is usually defined on a Maddrey Discriminant Function > 32. The Lille score at day 7 is used to decide whether corticosteroid therapy should be stopped or continued for a 1 month course. Nutritional supplementation is also likely to be beneficial. The main progress in better understanding its pathophysiology has come from cytokine studies. Various proinflammatory cytokines such as tumor necrosis factor-alpha (TNF?) or interleukin-1 (IL-1) have been proposed to play a role in this disease. This advancement has recently led to pilot studies investigating anti-TNF drugs such as pentoxifylline, infliximab (anti-TNF antibody) or etanercept in the treatment of this disease. These studies revealed besides for pentoxifylline rather negative results. Despite this fact, targeting of certain cytokines such as IL-1 remains an attractive treatment concept for this devastating disorder in the future. PMID:23842647
Wieser, Verena; Tilg, Herbert
Acute hepatic failure in children.
Many diseases may present as acute hepatic failure in the pediatric age group, including viral hepatitis A and B, adverse drug reactions, both toxic and "hepatitic," and inherited metabolic disorders such as tyrosinemia, alpha 1 antitrypsin deficiency, and Wilson's disease. Management is primarily supportive, with care taken to anticipate the known complications of hepatic failure. Few "curative" therapies are known, although attempts at stimulating hepatic regeneration may be helpful. Images FIG. 1 FIG. 3 FIG. 4
Riely, C. A.
Alcoholic hepatitis: A comprehensive review of pathogenesis and treatment
Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality. Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism, inflammation and innate immunity. Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH; such as Child-Turcotte-Pugh score, the Maddrey discriminant function, the Lille Model, the model for end stage liver disease scores, and the Glasgow alcoholic hepatitis score. At present, Corticosteroids or pentoxifylline are the current pharmacologic treatment options; though the outcomes from the therapies are poor. Liver transplantation as the treatment of alcoholic hepatitis remains controversial, and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option. Because of the limitations in the therapeutic options, it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH.
Chayanupatkul, Maneerat; Liangpunsakul, Suthat
Peculiar characteristics of portal-hepatic hemodynamics of alcoholic cirrhosis
Alcohol-related cirrhosis is a consequence of heavy and prolonged drinking. Similarly to patients with cirrhosis of other etiologies, patients with alcoholic cirrhosis develop portal hypertension and the hepatic, splanchnic and systemic hemodynamic alterations that follow. However, in alcoholic cirrhosis, some specific features can be observed. Compared to viral cirrhosis, in alcohol-related cirrhosis sinusoidal pressure is generally higher, hepatic venous pressure gradient reflects portal pressure better, the portal flow perfusing the liver is reduced despite an increase in liver weight, the prevalence of reversal portal blood flow is higher, a patent paraumbilical vein is a more common finding and signs of hyperdynamic circulations, such as an increased cardiac output and decreased systemic vascular resistance, are more pronounced. Moreover, alcohol consumption can acutely increase portal pressure and portal-collateral blood flow. Alcoholic cardiomyopathy, another pathological consequence of prolonged alcohol misuse, may contribute to the hemodynamic changes occurring in alcohol-related cirrhosis. The aim of this review was to assess the portal-hepatic changes that occur in alcohol-related cirrhosis, focusing on the differences observed in comparison with patients with viral cirrhosis. The knowledge of the specific characteristics of this pathological condition can be helpful in the management of portal hypertension and its complications in patients with alcohol-related cirrhosis.
Bolognesi, Massimo; Verardo, Alberto; Di Pascoli, Marco
This review will focus on the prevalence of hepatitis c virus (HCV) infection in alcoholics with and without liver disease. Evidence will be presented to demonstrate that ethanol and chronic HCV infection synergistically accelerate liver injury. Some of the major postulated mechanisms responsible for disease progression include high rates of apoptosis, lipid peroxidation, and generation of free radicals and reactive oxygen species with reduced antioxidant capacity of the liver. Acquisition and persistence of HCV infection may be due to the adverse effects of ethanol on humoral and cellular immune responses to HCV. Dendritic cells (DC) appear to be one of the major targets for ethanolÆs action and DC dysfunction impairs the ability of the host to generate viral specific cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) immune responses. There is a relationship between increased alcohol intake and decreased response to interferon (IFN) therapy, which may be reversed by abstinence. Clinical studies are needed to optimize treatment responses in alcoholic patients with chronic HCV infection.
Siu, Larry; Foont, Julie; Wands, Jack R.
Hepatic glutathione content in patients with alcoholic and non alcoholic liver diseases
Reduced and oxidized hepatic glutathione was evaluated during alcoholic and non alcoholic liver injury. We studied 35 chronic alcoholics, 20 patients with non alcoholic liver diseases, 15 control subjects. Hepatic glutathione was measured in liver biopsies and correlated with histology and laboratory tests. Alcoholic and non alcoholic patients exhibited a significant decrease of hepatic glutathione compared to control subjects. Oxidized
E. Altomare; G. Vendemiale; O. Albano
Hepatic glutathione content in patients with alcoholic and non alcoholic liver diseases
Reduced and oxidized hepatic glutathione was evaluated during alcoholic and non alcoholic liver injury. We studied 35 chronic alcoholics, 20 patients with non alcoholic liver diseases, 15 control subjects. Hepatic glutathione was measured in liver biopsies and correlated with histology and laboratory tests. Alcoholic and non alcoholic patients exhibited a significant decrease of hepatic glutathione compared to control subjects. Oxidized glutathione was significantly higher in the two groups of patients compared to controls. The decreased hepatic glutathione level in patients with alcoholic and non alcoholic liver diseases may represent a contributing factor of liver injury and may enhance the risk of toxicity in these patients.
Altomare, E.; Vendemiale, G.; Albano, O.
Acute Hepatitis A-Associated Acute Renal Failure in Adults
Background\\/Aims: The development of acute renal failure (ARF) is a very rare complication in patients with acute hepatitis A (AHA). Methods: We retrospectively investigated the overall incidence, risk factors, and clinical outcomes of ARF associated with AHA. Diagnosis of AHA was made according to the typical hepatitis symptoms and positivity of immunoglobulin M anti-hepatitis A virus in 208 patients with
Su Hyun Kim; Hye Eun Yoon; Yong Kyun Kim; Jin Young Kim; Bum Soon Choi; Young Jin Choi; Young Ok Kim; Yong Soo Kim; Byung Kee Bang; Chul Woo Yang
[Hepatic pseudotumor in acute fascioliasis].
We report a 61-year-old woman who was hospitalized because of abdominal pain in the right upper quadrant related to a liver tumor (ultrasound and tomographic findings). A collection of blood was obtained by a biopsy and there were no tumor cells. With the suspicion of acute fascioliasis (liver stage), due to severe eosinophilia and recent travel to endemic area of Fasciola hepatica, arc II and ELISA Fas 2 we carried out and were positive. Parasitological stool examinations were negative. During hospitalization a hepatic subcapsular hematoma presented as a complication and the patient developed fever because of cholangiolitic microabscesses in the left hepatic lobe. Percutaneous drainage was performed and positive cultures of secretions were obtained She received antibiotic coverage with vancomycin and imipenem. Treatment for Fasciola hepatica was initiated with nitaxozanida but it was discontinued due to oral intolerance. Later, she received a single dose of 250 mg triclabendazole with clinical and laboratory improvement. We presented this case because it is an unusual pseudotumoral presentation in acute hepatic fascioliasis. This parasitic disease is an emerging zoonosis in Per·. PMID:23650836
Castillo Contreras, Ofelia Brisaida; Frisancho Velarde, Oscar
Acute hepatitis E complicated by acute pancreatitis and multiorgan dysfunction.
We report this rare case of a 27-year-old man who presented with acute hepatitis E and went on to develop acute epigastric pain. He was diagnosed to have acute severe pancreatitis with shock and acute renal failure due to hepatitis E. Such a phenomenon has rarely been reported in the literature, with patients following a benign course and complete recovery after conservative management and analgesia. Awareness of this potentially life-threatening complication, especially in young men from endemic areas with acute hepatitis E presenting with abdomen pain has been highlighted. PMID:24899005
Karanth, Suman S; Khan, Zohaib; Rau, Nileshwar Radhakrishna; Rao, Karthik
Acute Sporadic Hepatitis E in Kuwait.
National Technical Information Service (NTIS)
Fifty-seven adult patients with acute hepatitis and 34 comparison patients without liver disease were evaluated using a newly developed Western blot assay for lgM antibody to hepatitis E virus. The mean age of patients with hepatitis was 32 years (range, ...
A. Koshy A. L. Richards S. Al-Mufti S. Grover M. A. Shabrawy
Viral Hepatitis-Related Acute Liver Failure
OBJECTIVES:Viral hepatitis has previously been the major cause of acute liver failure (ALF) in the United States. We aimed to determine the incidence of viral hepatitis-related ALF and to compare the outcome and clinical and biochemical variables in patients with hepatitis A and B.METHODS:A total of 354 patients with ALF from multiple centers were screened for possible acute viral etiology.RESULTS:Forty-three
Frank Vinholt Schi°dt; Timothy J. Davern; A. Obaid Shakil; Brendan McGuire; Grace Samuel; William M. Lee
Acute alcohol intoxication and female orgasmic response
This study tested the hypothesis that increasing levels of acute alcohol intoxication are related to systematic changes in female orgasmic experience reflected by physiological, behavioral, and cognitive indices. Using a repeated measures design with monthly experimental sessions, each of 18 university women were sustained at four different blood alcohol concentrations (BAC) in counterbalanced order prior to viewing sexually explicit videotapes
Victor J. Malatesta; Robert H. Pollack; Terri D. Crotty; Lelon J. Peacock
Extracorporeal liver support in severe alcoholic hepatitis
The severity of alcoholic hepatitis (AH) which may coexist with cirrhosis varies greatly, from asymptomatic forms which are detected in alcoholic patients without any sign of liver disease, except laboratory abnormalities, to severe forms characterised by deep jaundice, ascites, hepatic encephalopathy and low prothrombin index. In hospitalized patients the mortality could be as high as 75%. The elevated number of therapeutic proposals reported for more than forty years reveals the lack of efficacy of a particular modality. Even in the most favorable trials, the survival is already very poor and in some cases related to the development of renal failure or hepatorenal syndrome. There are some motivating reports concerning albumin dialysis as a support treatment in patients with severe AH, either alone or in combination with other pharmacological therapies. The favorable effects of albumin dialysis in patients with severe AH suggest that the procedure used alone or in combination with other therapies may have a role in this clinical condition. This will be particularly relevant to offer an alternative therapy in these patients, thus being a potential bridge to recovery or to be listed for liver transplantation.
Pares, Albert; Mas, Antoni
Acute pancreatitis: a rare complication of acute hepatitis E.
Hepatitis E is an emerging imported disease in Europa but autochthonous cases are described for some years. Extra-hepatic associated manifestations are published. We report a case of acute necrotizing pancreatitis associated with imported acute viral E hepatitis (genotype 1a) in a 26 years old French man travelling and originated from Pakistan. The outcome is favourable spontaneously in two months. This life-threatening hepatitis E related complication is unknown in Europa where genotype 3 virus strains prevail. The clinical presentation is stereotyped with the onset of pancreatitis in the second or third weeks of hepatitis evolution in an Indian male in his second or third decade infected with genotype 1 strain. No pancreatitis-related death is reported in the 13 previous reported cases. PMID:21628104
Deniel, Cķcile; Coton, Thierry; Brardjanian, Sarah; Guisset, Michel; Nicand, Elisabeth; Simon, Fabrice
Animal models of acute hepatic failure
The understanding and treatment of acute hepatic failure has developed rapidly over the last 40 years reducing morbidity and mortality from this syndrome. Progress has been made by the study of animal models that reflect the clinical, biochemical and histological pattern of the syndrome seen in man. This is of increasing importance with the use of therapeutic intervention, liver transplantation and the use of extra-corporeal liver support devices. This review examines and critically appraises the various approaches to the study of acute hepatic failure in animal models, including both surgical and pharmacological approaches.
Rahman, Tony Manibur; Hodgson, Humphrey J F
Alcoholic hepatitis 2010: A clinician's guide to diagnosis and therapy
Alcoholic hepatitis (AH) remains a common and life threatening cause of liver failure, especially when it is severe. Although the adjective ōacuteö is frequently used to describe this form of liver injury, it is usually subacute and has been developing for weeks to months before it becomes clinically apparent. Patients with this form of alcoholic liver disease usually have a history of drinking heavily for many years. While certain aspects of therapy, mainly nutritional support and abstinence are well established, significant debate has surrounded the pharmacologic treatment of AH, and many institutions practice widely varying treatment protocols. In recent years a significant amount of literature has helped focus on the details of treatment, and more data have accumulated regarding risks and benefits of pharmacologic treatment. In particular, the efficacy of pentoxifylline has become increasingly apparent, and when compared with the risks associated with prednisolone, has brought this drug to the forefront of therapy for severe AH. This review will focus on the clinical and laboratory diagnosis and pharmacologic therapies that should be applied during hospitalization and continued into outpatient management. We conclude that the routine use of glucocorticoids for severe AH poses significant risk with equivocal benefit, and that pentoxifylline is a better, safer and cheaper alternative. While the full details of nutritional support lie beyond the scope of this article, nutrition is a cornerstone of therapy and must be addressed in every patient diagnosed with AH. Finally, while traditional psychosocial techniques play a major role in post-hospitalization care of alcoholics, we hope to make the medical clinician realize his or her role in reducing recidivism rates with early and frequent outpatient visits and with the use of baclofen to reduce alcohol craving.
Amini, Maziyar; Runyon, Bruce A
Albendazole-induced associated acute hepatitis and bicytopenia.
Acute hepatitis induced by albendazole is rarely reported. We describe herein an original case of acute hepatitis associated with bicytopenia after albendazole intake. This paper is the first to describe a possible association of a hematologic disorder and acute hepatitis, both induced by albendazole therapy. PMID:24423162
Ben Fredj, Nadia; Chaabane, Amel; Chadly, Zohra; Ben Fadhel, Najeh; Boughattas, Naceur A; Aouam, Karim
Protective effect of bicyclol on acute alcohol-induced liver injury in mice
Oxidative stress, cytokine over expression and Kupffer cell activation are well-documented pathological factors in the development of alcoholic liver disease. Bicyclol is a novel synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory property. The present study was to investigate the effect of bicyclol on acute alcohol-induced liver injury and related mechanisms in mice. Bicyclol (200, 300Āmg\\/kg) was given to mice by
Jing Zhao; Hui Chen; Yan Li
The aetiology of acute viral hepatitis among some Egyptian youth.
Sero-diagnosis for HA, B, C & D were determined among acute hepatitis in 99 male military recruits, admitted to MOH Fever Hospital. Their ages ranged from 18-25 years. The results showed that hepatitis A was 1%, hepatitis B was 52%, acute hepatitis on HBsAg carrier was 3%, and hepatitis C was 8%. Among acute B 3% had anti-delta antibody. Anti-HCV was found in 2/5 of cases with acute hepatitis in HBsAg carriers, 4/21 of cases with past exposure of HBV and in 2/18 of cases negative for HBV. PMID:22662609
Badawy, Alfy Amine; Khalil, Hazim H M
Impaired plasma lipid profiles in acute hepatitis
The present study examined plasma lipid profiles in thirty patients suffered from acute viral hepatitis. Patients' blood samples were collected at both the debut and recovery of diseases. Thirty sex and age matched normal subjects were included as controls. Plasma total triglycerides (TG), total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), lipoprotein (a) (Lp(a)), blood coagulation status including prothrombin complex activity and activated partial tromboplastin time (APTT), and hepatic functions were determined by the automatic biochemical analytical instrument. It demonstrated that plasma levels of total cholesterol, HDL-C and apoAI were significantly lower in the patients at the acute phase of hepatitis than those in normal subjects, whereas plasma levels of TG and LDL-C were obviously higher in the patients than in normal subjects (P < 0.05). Moreover, we demonstrated that patients' plasma levels of total cholesterol, LDL-C, HDL-C and apoAI were lower at the active phase of the diseases than at the recovering phase, which indicating that acute liver damage could significant influence lipid metabolism in vivo. No pathological changes of blood coagulation status occurred in these patients during the study as all selected patients had moderate hepatitis. It may conclude that examinations of plasma lipid profile could be considered as a clinical index to reflect liver damage in the active phase of hepatitis.
Lipid peroxidation and hepatic antioxidants in alcoholic liver disease.
The generation of hepatic liver peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. To investigate this hypothesis, lipid extracts from hepatic needle biopsy specimens from alcoholic subjects were examined for evidence of lipid peroxidation by measuring total conjugated dienes by derivative spectroscopy and, after hydrolysis of hepatic lipid extract and reverse phase high performance liquid chromatography, the molar ratio between a diene-conjugated linoleic acid isomer (18:2 (9,11)) and the parent linoleic acid isomer (18:2(9,12)). Changes were related to hepatic histology, iron deposition, glutathione and vitamin E values. Derivative spectroscopy minima suggestive of diene conjugation were identified at 233 and 242 nm and correlated weakly, suggesting these two minima may represent different classes of lipid dienes. There was a weak relation with inflammatory histological changes in the biopsy specimen but no correlation with hepatic iron grade, glutathione, or vitamin E lipid ratio. The proportion of 18:2(9,11) linoleic acid in hepatic lipids correlated significantly with inflammatory histological features and inversely with hepatic glutathione. Furthermore, hepatic glutathione was lower in biopsy specimens with greater iron staining. The ratio of vitamin E to lipid was not related to histological group, inflammation, or iron grade. These findings suggest that excess alcohol consumption leads to hepatic inflammation and lipid peroxidation.
Situnayake, R D; Crump, B J; Thurnham, D I; Davies, J A; Gearty, J; Davis, M
Impaired cerebral autoregulation during acute alcohol withdrawal.
Heavy alcohol consumption increases the risk for all major types of stroke and is associated with autonomic dysfunction during alcohol withdrawal syndrome (AWS). Cerebral autoregulation is the mechanism by which cerebral perfusion is maintained stable, representing an intrinsic protective system of the cerebral circulation. Here, we aimed to analyze the influence of acute AWS on cerebral hemodynamics in alcohol-dependent patients. We investigated 20 men in the unmedicated acute state of AWS and repeated the investigation 24h after initiation of clomethiazole treatment. Dynamic cerebral autoregulation (dCA) was assessed by the correlation coefficient index and transfer function analysis (phase and gain) from oscillations of arterial blood pressure and cerebral blood flow velocity (CBFV). The vasomotor reserve (VMR) was measured by the CO(2)-reactivity test. In addition, we assessed autonomic modulation by means of heart rate variability and baroreflex sensitivity. We observed impaired dynamic autoregulation as shown by a multivariate analysis of variance (p<0.038) including all parameters of dCA. Similar results were found for VMR at admission (p<0.05). Pair-wise comparison between baseline and treatment with clomethiazole revealed a significant improvement for the systolic correlation coefficient index (Sx; p<0.001). Furthermore, we found a strong association of autonomic dysfunction and impaired autoregulation indicated by a correlation between the LF/HF ratio and Sx (p<0.001). In conclusion, cerebral autoregulation and VMR are disturbed during acute AWS. Influences of autonomic dysbalance and mental state during withdrawal are suggested. The finding of an affected autoregulation during acute withdrawal might indicate an increased risk for cerebro-vascular disease. PMID:20456871
Jochum, Thomas; Reinhard, Matthias; Boettger, Michael K; Piater, Maik; Bõr, Karl-J³rgen
In vitro and in vivo models of acute alcohol exposure
Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute alcohol consumption also affects human wellbeing. Thus, there is a need for research models in order to fully understand the effect of acute alcohol abuse on different body systems and organs. The present manuscript summarizes the interdisciplinary advantages and disadvantages of currently available human and non-human models of acute alcohol abuse, and identifies their suitability for biomedical research.
Dolganiuc, Angela; Szabo, Gyongyi
A mathematical model for acute hepatitis B virus infection
Based on the clinical data of acute hepatitis B patients and the HBV infection dynamic model proposed by Nowak et al., we construct a mathematical model to describe and understand the dynamics of host cells, virus and the immune system during the acute stages of the infection. Our model provide a possible interpretation for the phenomenon of acute hepatitis and
Lijuan Du; Dongwei Huang; Qizhi Xie
Bermuda Triangle for the liver: alcohol, obesity, and viral hepatitis.
Despite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end-stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy. PMID:23855291
Zakhari, Samir
Relationship between hepatitis C virus subtypes and clinical features of liver disease seen in alcoholics
The influence of hepatitis C virus and its subtypes on the clinical course of liver disease in alcoholics was assessed. Hepatitis C virus infection was confirmed by a reverse transcription and polymerase chain reaction method for the hepatitis C virus NS-5 region in the sera of the alcoholics with various stages of histologically proven liver disease.The frequency of hepatitis C
Hirokazu Yokoyama; Hiromasa Ishii; Susumu Moriya; Shigeyuki Nagata; Tetsu Watanabe; Kiyotaka Kamegaya; Hisao Takahashi; Katsuya Maruyama; Paul Haber; Masaharu Tsuchiya
[A case of sustained cholestasis caused by acute A viral hepatitis in Dubin-Johnson syndrome].
Dubin-Johnson syndrome is a rare clinical entity. It shows intermittent symptoms such as chronic or intermittent jaundice, abdominal pain, weakness, nausea, vomiting, anorexia and diarrhea. Symptoms are precipitated or aggravated by pregnancy, alcoholism, surgical procedures and intercurrent disease. Chronic idiopathic jaundice is typical of Dubin-Johnson syndrome and its prognosis is good. We describe a case of prolonged cholestasis for more than 10 months caused by acute A viral hepatitis in a patient with Dubin-Johnson syndrome. It is a first report of cholestasis complicated by acute A viral hepatitis in a patient with Dubin-Johnson syndrome. PMID:22544030
Ra, Sang Ho; Sung, Se Yong; Jung, Ho Yeon; Cha, Jae Hwang; Baik, Soon Koo; Cho, Mee Yon; Kim, Moon Young
[Diclofenac-associated acute cholestatis hepatitis].
Diclofenac is an anti-inflammatory analgesic which is widely used in the therapy of inflammatory joint pain. Diclofenac hepatotoxicity ranges from asymptomatic elevation of transaminase activity to significant liver disease. 31 cases of diclofenac-induced hepatitis with five associated deaths have been already reported in the English, French and Spanish literature. We report the case of a 64-year-old patient who was admitted to the hospital with an icteric hepatitis of sudden onset. The only drug that was taken before admission was diclofenac in a daily dose of 150-200 mg because of a spondylodiscitis. Work-up of the patient included ERCP, laparoscopy and liver biopsy and excluded other reasons of a cholestatic hepatitis. Discontinuation of diclofenac resulted in normalization of transaminase activity and bilirubin concentration within four months. The frequent use of diclofenac and the possibility of fatal liver damage highlights the need that diclofenac-toxicity should be considered in the differential diagnosis of acute cholestatic hepatitis. PMID:9654706
Hackstein, H; Mohl, W; P³schel, W; Stallmach, A; Zeitz, M
Acute encephalomyelitis associated with acute viral hepatitis type B.
We describe the case of a 36-year-old woman who developed acute encephalo-myelitis after acute viral hepatitis type B. She was admitted to the hospital with a history of general malaise and nausea of 5 days duration. Her serum showed high transaminase levels and positive HBs-Ag and increased IgM HBc-Ab titers. She had urinary dysfunction, myoclonus and postural tremor of her extremities. Several days later, she developed bilateral limb ataxia and alteration of consciousness. The cerebrospinal fluid examinations showed pleocytosis and increased protein. Treatment with high-dose methylprednisolone resulted in a marked improvement of the clinical and CSF examination. Magnetic resonance imaging of the brain and the spinal cord did not disclose abnormal lesions. The symptoms and clinical course were quite similar to those of acute disseminated encephalomyelitis. PMID:19218776
Kinomoto, Keiko; Okamoto, Yoshinobu; Yuchi, Yuichiro; Kuriyama, Masaru
Acute glomerulonephritis in hepatitis A virus infection: a rare presentation.
An eight-year-old boy presenting with features of acute glomerulonephritis (AGN), developed jaundice. He was positive for hepatitis A immunoglobulin M. AGN is a rare complication of hepatitis A. Here, we describe a temporal association of hepatitis A infection complicated by AGN. PMID:19535765
Aggarwal, Anju; Kumar, Devendra; Kumar, Ritesh
Increased severity and morbidity of acute hepatitis in drug abusers with simultaneously acquired hepatitis B and hepatitis D virus infections.
Hepatitis D virus (delta agent) markers were present in 111 (36%) of 308 intravenous drug abusers who were positive for hepatitis B surface antigen (HBsAg), 52 of these having hepatitis D virus antigenaemia. IgM antibody to hepatitis B core antigen (anti-HBc IgM) was present in 92 out of 95 subjects tested, indicating that hepatitis D virus and hepatitis B virus infections had been acquired simultaneously. Hepatitis D virus markers were present in three out of four patients with fulminant hepatitis, and in 80 of 223 (36%) with mild or moderate hepatitis compared with four of 29 (14%) of those who were asymptomatic. These proportional differences were significant (p less than 0.001). Hepatitis D virus markers were present in twice as many patients positive for anti-HBc IgM requiring admission to hospital with acute hepatitis compared with outpatients attending a drug treatment centre. Tests on one patient showed complete disappearance of HBsAg, but hepatitis D antigen (HDAg or delta antigen) and hepatitis B e antigen (HBeAg) were still present in serum samples. All five patients with chronic active hepatitis had hepatitis D antibody (anti-HD) compared with seven of 24 (29%) with chronic persistent hepatitis (p = 0.008). Blocking anti-HD persisted for long periods after simultaneous infections with hepatitis B virus and hepatitis D virus but at lower titres than in patients with chronic liver disease.
Shattock, A G; Irwin, F M; Morgan, B M; Hillary, I B; Kelly, M G; Fielding, J F; Kelly, D A; Weir, D G
Disturbances in the murine hepatic circadian clock in alcohol-induced hepatic steatosis
To investigate the role of the circadian clock in the development of alcohol-induced fatty liver disease we examined livers of mice chronically alcohol-fed over 4-weeks that resulted in steatosis. Here we show time-of-day specific changes in expression of clock genes and clock-controlled genes, including those associated with lipid and bile acid regulation. Such changes were not observed following a 1-week alcohol treatment with no hepatic lipid accumulation. Real-time bioluminescence reporting of PERIOD2 protein expression suggests that these changes occur independently of the suprachiasmatic nucleus pacemaker. Further, we find profound time-of-day specific changes to the rhythmic synthesis/accumulation of triglycerides, cholesterol and bile acid, and the NAD/NADH ratio, processes that are under clock control. These results highlight not only that the circadian timekeeping system is disturbed in the alcohol-induced hepatic steatosis state, but also that the effects of alcohol upon the clock itself may actually contribute to the development of hepatic steatosis.
Zhou, Peng; Ross, Ruth A.; Pywell, Cameron M.; Liangpunsakul, Suthat; Duffield, Giles E.
The management of acute dental pain in the recovering alcoholic.
Although there have been many advances in our understanding of the neurophysiology of pain, the management of acute pain continues to be a challenge. When the need arises to provide adequate and effective pain management for the recovering alcoholic, the problem becomes much more complex. The clinician must provide the patient with adequate analgesia without causing a relapse. In the US, 6% to 10% of the population has attended Alcoholics Anonymous at some point, increasing the likelihood of the clinician being faced with the need to manage acute pain in a recovering alcoholic. The purpose of this article is to suggest guidelines for the management of acute dental pain in the recovering alcoholic based on current principles of acute pain management and for the treatment of pain in addicted patients. PMID:12686926
Lindroth, John E; Herren, M Chris; Falace, Donald A
[Acute hepatic failure after ingestion of mushrooms].
This report is about a married couple who were admitted to hospital suffering from gastrointestinal complaints after eating mushrooms. With the suspicion of poisoning with Amanita phalloides treatment started with elimination of the toxins, symptomatic therapy and specific therapy with silibinin. After quantitative determination of the Amanita toxins the patients were immediately transferred to a university hospital.Poisoning by the death cap mushroom is responsible for acute hepatic and often also renal failure and is accompanied by a high mortality. Clinical symptoms follow a three-phase course with gastrointestinal complaints, an asymptomatic interval and finally the hepatorenal phase. Even in suspected cases of intoxication, treatment should be started by antidote therapy with silibinin. PMID:22527661
Oeckinghaus, R; Cuneo, A; Brockmeier, J; Oeckinghaus, G S; Drewek-Platena, S; Hochreuther, St; G÷tz, J; Tebbe, U
T cell subsets in patients with acute and chronic HBV infection, primary biliary cirrhosis and alcohol induced liver disease.
The proportions of inducer and cytotoxic/suppressor T cells and their concentration in peripheral blood have been determined in patients with acute and chronic type B hepatitis, hepatitis B virus (HBV) carriers with normal hepatic histology, patients with alcohol-induced liver disease (ALD), primary biliary cirrhosis (PBC) and chronic extrahepatic cholestasis. During acute type B hepatitis the inducer/suppressor ratio was decreased due to an increase in suppressor cell concentrations. When this ratio returned to normal the HBs antigen was cleared and HBs antibody was detectable. Similar abnormalities were found in patients with HBs + ve chronic hepatitis. In HBs antigen-positive patients with normal histology, normal T cell subsets were found. In some patients with primary biliary cirrhosis the ratio of inducer to suppressor cells was low due to a reduction in the concentration of inducer cells and in others high due to a reduction in suppressor cells. Administration of cyclosporin A to the latter group produced an increase in the concentration of suppressor cells and there was an improvement in liver biochemistry. In alcohol-induced hepatitis and cirrhosis the ratio of inducer/suppressor cells was normal. Whether these imbalances of the regulatory cells of the immune system in patients with chronic HBV-induced hepatitis and PBC are of primary or secondary importance is uncertain. The relationship of the depressed ratio to persistence of the hepatitis B virus is worthy of further study. PMID:6457007
Thomas, H C
Alcohol Fuels Liver Disease in Those with HIV and Hepatitis C
Acute paternal alcohol use affects offspring development and adult behavior
Swiss Webster pups were fathered by sires given either an acute dose of alcohol (alcohol-sired) or saline (saline-sired) 12¢24Āh before mating. The same sires were used to father both groups of pups. Alcohol-sired pups were significantly lighter at birth and for the following three weeks than were saline-sired pups. Significantly more pups were fathered by saline-exposed sires, and dams carrying
Leslie R. Meek; Kirsten Myren; Juliane Sturm; Dawn Burau
Role of osteopontin in hepatic neutrophil infiltration during alcoholic steatohepatitis
Alcoholic liver disease (ALD) is a major complication of heavy alcohol (EtOH) drinking and is characterized by three progressive stages of pathology: steatosis, steatohepatitis, and fibrosis/cirrhosis. Alcoholic steatosis (AS) is the initial stage of ALD and consists of fat accumulation in the liver accompanied by minimal liver injury. AS is known to render the hepatocytes increasingly sensitive to toxicants such as bacterial endotoxin (LPS). Alcoholic steatohepatitis (ASH), the second and rate-limiting step in the progression of ALD, is characterized by hepatic fat accumulation, neutrophil infiltration, and neutrophil-mediated parenchymal injury. However, the pathogenesis of ASH is poorly defined. It has been theorized that the pathogenesis of ASH involves interaction of increased circulating levels of LPS with hepatocytes being rendered highly sensitive to LPS due to heavy EtOH consumption. We hypothesize that osteopontin (OPN), a matricellular protein (MCP), plays an important role in the hepatic neutrophil recruitment due to its enhanced expression during the early phase of ALD (AS and ASH). To study the role of OPN in the pathogenesis of ASH, we induced AS in male Sprague-Dawley rats by feeding EtOH-containing Lieber-DeCarli liquid diet for 6 weeks. AS rats experienced extensive fat accumulation and minimal liver injury. Moderate induction in OPN was observed in AS group. ASH was induced by feeding male Sprague-Dawley rats EtOH-containing Lieber-DeCarli liquid diet for 6 weeks followed by LPS injection. The ASH rats had substantial neutrophil infiltration, coagulative oncotic necrosis, and developed higher liver injury. Significant increases in the hepatic and circulating levels of OPN was observed in the ASH rats. Higher levels of the active, thrombin-cleaved form of OPN in the liver in ASH group correlated remarkably with hepatic neutrophil infiltration. Finally, correlative studies between OPN and hepatic neutrophil infiltration was corroborated in a simple rat peritoneal model where enhanced peritoneal fluid neutrophil infiltration was noted in rats injected OPN intraperitoneally. Taken together these data indicate that OPN expression induced during ASH may play a significant role in the pathogenesis of ASH by stimulating neutrophil transmigration.
Apte, Udayan M. [Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, MS4467, College Station, TX 77843-4467 (United States); Banerjee, Atrayee [Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, MS4467, College Station, TX 77843-4467 (United States); McRee, Rachel [Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, MS4467, College Station, TX 77843-4467 (United States); Wellberg, Elizabeth [Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, MS4467, College Station, TX 77843-4467 (United States); Ramaiah, Shashi K. [Department of Pathobiology, College of Veterinary Medicine, Texas A and M University, MS4467, College Station, TX 77843-4467 (United States)]. E-mail: email@example.com
Acute polymyositis during treatment of acute hepatitis C with pegylated interferon alpha-2b.
Hepatitis C virus is not cleared after primary infection in 50-85% of subjects exposed to hepatitis C virus. Anti-viral treatment during the early phase of infection significantly enhances the likelihood of a sustained clearance of hepatitis C virus. Although, a variety of autoimmune-related side effects have been observed during interferon therapy for chronic hepatitis, immuno-mediated adverse reactions have not been reported during treatment of acute hepatitis C. We describe the case of a patient who developed acute hepatitis C virus infection and, while receiving pegylated interferon alpha-2b monotherapy, developed a severe polymyositis. This case illustrates the potential risk of autoimmunity by interferon, also for acute hepatitis, and underlines the importance of a prompt diagnosis and a rapid discontinuation of interferon treatment for an improvement of clinical outcomes. PMID:16169301
Venezia, G; Licata, A; Di Marco, V; Craxņ, A; Almasio, P L
[Subclinical acute intermittent porphyria. An uncommon cause of chronic hepatitis].
Acute porphyria is a term that encompasses a group of hereditary disorders involving defects in heme metabolism, characterized by acute episodes of abdominal pain, acute hypertension, tachycardia and neuropsychiatric disorders, sometimes leading to convulsions, ascending paralysis and coma. Misdiagnosis or delayed diagnosis can seriously worsen prognosis. We report the case of a woman with subclinical acute intermittent porphyria and chronic hepatitis incidentally diagnosed due to transaminase elevation on laboratory analysis. PMID:21477889
Pķrez MartĒnez, Juan; Castro Mßrquez, Cristina; Pereira Gallardo, SofĒa; Jimķnez Sßenz, Manuel; HerrerĒas Gutiķrrez, Juan Manuel
Pharmacodynamic Effects of Intravenous Alcohol on Hepatic and Gonadal Hormones: Influence of Age and Sex
Background Growth Hormone (GH) - Insulin-like Growth Factor 1 (IGF-1) axis and gonadal hormones demonstrate extensively associated regulation; however, little is known about the effects of acute alcohol exposure on these hormones. This study examined the effects of intravenous alcohol on the GH¢IGF-1 axis and gonadal hormone concentrations, and the influence of age and sex on their regulation. Methods Forty-eight healthy volunteers (24 males and 24 females each in the 21¢25 and 55¢65 year age groups, underwent a two-session single-blinded study. Subjects received, in randomized counter-balanced order, alcohol infusions, individually computed based on a physiologically-based pharmacokinetic (PBPK) model, to maintain a steady-state (ōclampedö) exposure of 50 mg% or saline for 3 hrs in separate sessions. Blood samples collected at baseline and post-infusion in each session were assayed for levels of GH, IGF-1, free testosterone and estradiol. Results Acute alcohol administration resulted in changes in gonadal hormones that differed by sex. Change in free testosterone showed a significant treatment ū baseline interaction (p<0.001), indicating that alcohol-induced suppression of testosterone occurred predominantly in males, On the other hand, change in estradiol showed a significant treatment ū sex interaction (p=0.028), indicating that alcohol-induced increases in estradiol occurred predominantly in females. There was a trend for alcohol-induced decreases in IGF-1 levels. Change in GH showed a significant main effect of baseline (p<0.001) and a trend for treatment by baseline interaction, suggesting an alcohol-induced decrease in individuals with high baseline GH values. There was also a significant main effect of sex (p=0.046) indicating that males had greater changes in GH across treatment compared to females. Conclusion Alcohol induced a complex pattern of hormonal responses that varied between younger and older males and females. Some of the observed sex-based differences may help improve our understanding of the greater susceptibility to alcohol-related hepatic damage seen in females.
Vatsalya, Vatsalya; Issa, Julnar E.; Hommer, Daniel W.; Ramchandani, Vijay A.
Nimesulide-induced acute hepatitis: evidence from six cases
Background\\/Aims: A number of nonsteroidal anti-inflammatory drugs have been reported to provoke hepatic injury. Nimesulide is a new agent of the sulfonanilide class, and is a more selective inhibitor of cyclooxygenase type 2 than of type 1. Well-documented cases of acute hepatitis have not yet been reported with this drug. We report on six patients who developed acute liver damage
Werner Van Steenbergen; Pascal Peeters; Joris De Bondt; Dirk Staessen; Henri B³scher; Thiery Laporta; Tania Roskams; Valeer Desmet
Steroids treatment of granulomatous hepatitis complicating Coxiella burnetii acute infection
SummaryĀĀGranulomatous hepatitis associated withCoxiella burnetii acute infection has an adverse clinical course in some patients. Surprisingly, it does not respond to antibiotic but to steroids\\u000a treatment. A hypersensitivity mechanism has been implicated. A case of granulomatous hepatitis complicatingC. burnetii acute infection is reported, which was refractory to antibiotics but, as in four other cases previously reported, showed\\u000a a complete response
M. Crespo; B. Sope±a; J. Bord¾n; J. de la Fuente; M. Rubianes; C. Martinez-Vßzquez
Aims: Little is known about how non-problematic drinkers respond to advice to reduce alcohol consumption as part of dis- ease management. In this article, we examine patient reports of drinking behaviour after being diagnosed with chronic hepatitis C, a condition for which alcohol consumption is contraindicated. Methods: In this qualitative study, we analyzed transcripts of semi- structured interviews with hepatitis
Molecular targets in the treatment of alcoholic hepatitis
Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflammatory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease.
Dhanda, Ashwin D; Lee, Richard WL; Collins, Peter L; McCune, C Anne
Alcohol exacerbates LPS-induced fibrosis in subclinical acute pancreatitis.
The role of pancreatic acinar cells in initiating fibrogenic responses during the early stages of alcoholic acute pancreatitis has not been evaluated. We investigated the ability of injured acinar cells to generate pancreatic fibrosis in acute pancreatitis. Rats were fed either an ethanol-containing or control diet over 14 weeks and euthanized 3 or 24 hours after a single lipopolysaccharide injection. Profibrotic transforming growth factor-? of acinar cells and pancreatic fibrosis were assessed by immunofluorescence, histological characteristics, and electron microscopy. Human pancreatic tissues were also evaluated. Periacinar cell fibrosis and collagen were exacerbated 24 hours after endotoxemia in alcohol-fed rats. Alcohol exposure exacerbated acinar cell-specific production of transforming growth factor ? in response to lipopolysaccharide in vivo and in acinar cell-like AR42J cells in vitro. Although a morphological examination showed no visible signs of necrosis, early pancreatic fibrosis can be initiated by little or no pancreatic necrosis. Transforming growth factor ? was also significantly increased in human acinar cells from patients with acute/recurrent pancreatitis compared with chronic pancreatitis tissue. Alcohol exacerbates lipopolysaccharide-induced pancreatic fibrosis during the early onset of mild, subclinical, acute pancreatitis. We suggest that multiple, subclinical, acute pancreatitis episodes can accumulate in fibrosis during the development of chronic pancreatitis, even if there is no history of acute pancreatitis. PMID:24091223
Gu, Haitao; Fortunato, Franco; Bergmann, Frank; B³chler, Markus W; Whitcomb, David C; Werner, Jens
Acute paternal alcohol use affects offspring development and adult behavior.
Swiss Webster pups were fathered by sires given either an acute dose of alcohol (alcohol-sired) or saline (saline-sired) 12-24 h before mating. The same sires were used to father both groups of pups. Alcohol-sired pups were significantly lighter at birth and for the following three weeks than were saline-sired pups. Significantly more pups were fathered by saline-exposed sires, and dams carrying those pups had significantly longer gestations than those carrying pups of alcohol-using sires. More runts were born to the alcohol-sired group, and more pups in that group died over the next three weeks than in the saline-sired group. Significantly more pups in the saline-sired group achieved such developmental milestones as surface righting, clinging, the tail-pull reflex, rotation, linear movement and climbing an inclined surface earlier than did alcohol-sired pups. As adults, animals from the alcohol-sired group showed significantly less risk assessment behavior and longer latencies to such behaviors as stretched attention, flatback, freezing and defensive burying than did the saline-sired animals. Alcohol-sired animals contacted the stimulus object in the risk assessment test significantly sooner and more often than did the saline-sired group. In tests of aggression, alcohol-sired male offspring showed more frequent aggressive behaviors such as on-top, lateral attacks and jump-attacks, and significantly fewer defensive/fearful behaviors such as piloerection, tail rattling and jump-escape. This pattern of results suggests that exposure of the sire to one acute dose of alcohol before insemination caused some early developmental delays and that alcohol-sired animals are less fearful and more aggressive as adults than saline-sired animals. PMID:17433387
Meek, Leslie R; Myren, Kirsten; Sturm, Juliane; Burau, Dawn
Improving Alcohol Withdrawal Outcomes in Acute Care
Context Excessive alcohol consumption is the nationÆs third leading cause of preventable deaths. If untreated, 6% of alcohol-dependent patients experience alcohol withdrawal, with up to 10% of those experiencing delirium tremens (DT), when they stop drinking. Without routine screening, patients often experience DT without warning. Objective: Reduce the incidence of alcohol withdrawal advancing to DT, restraint use, and transfers to the intensive care unit (ICU) in patients with DT. Design: In October 2009, the alcohol withdrawal team instituted a care management guideline used by all disciplines, which included tools for screening, assessment, and symptom management. Data were obtained from existing datasets for three quarters before and four quarters after implementation. Follow-up data were analyzed and showed a great deal of variability in transfers to the ICU and restraint use. Percentage of patients who developed DT showed a downward trend. Main Outcome Measures: Incidence of alcohol withdrawal advancing to DT and, in patients with DT, restraint use and transfers to the ICU. Results: Initial data revealed a decrease in percentage of patients with alcohol withdrawal who experienced DT (16.4%¢12.9%). In patients with DT, restraint use decreased (60.4%¢44.4%) and transfers to the ICU decreased (21.6%¢15%). Follow-up data indicated a continued downward trend in patients with DT. Changes were not statistically significant. Restraint use and ICU transfers maintained postimplementation levels initially but returned to preimplementation levels by third quarter 2012. Conclusion: Early identification of patients for potential alcohol withdrawal followed by a standardized treatment protocol using symptom-triggered dosing improved alcohol withdrawal management and outcomes.
Melson, Jo; Kane, Michelle; Mooney, Ruth; McWilliams, James; Horton, Terry
Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model
Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for ?-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-?1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-?1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection.
Noh, Dong-Hyung; Lee, Eun-Joo; Kim, Ah-Young; Lee, Eun-Mi; Min, Chang-Woo; Kang, Kyung-Ku; Lee, Myeong-Mi; Kim, Sang-Hyeob; Sung, Soo-Eun; Hwang, Meeyul; Yu, Dae-Yeul; Jeong, Kyu-Shik
Alcohol induced hepatic degeneration in a hepatitis C virus core protein transgenic mouse model.
Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for ?-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-?1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-?1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection. PMID:24608925
Noh, Dong-Hyung; Lee, Eun-Joo; Kim, Ah-Young; Lee, Eun-Mi; Min, Chang-Woo; Kang, Kyung-Ku; Lee, Myeong-Mi; Kim, Sang-Hyeob; Sung, Soo-Eun; Hwang, Meeyul; Yu, Dae-Yeul; Jeong, Kyu-Shik
Acute effects of alcohol on the development of intrusive memories
RationaleĀĀPost-traumatic stress disorder is characterised by repeated intrusive imagery of the traumatic event. Despite alcohol's impairing\\u000a effect on memory and frequent involvement in real-life trauma, virtually nothing is known of the interaction between alcohol\\u000a and trauma memory.\\u000a \\u000a \\u000a \\u000a ObjectiveĀĀWe aimed to investigate the acute alcohol effects on spontaneous memories following a trauma film as well as explicit memory\\u000a for the film.
James A. Bisby; Chris R. Brewin; Julie R. Leitz; H. Valerie Curran
An acute psychosocial stressor does not potentiate alcohol cue reactivity in non-treatment-seeking alcoholics
Background Relapse risk factors, such as psychological stress and alcohol cues, are often encountered together. Understanding how they interact has the potential to improve alcoholism treatments. The present study was conducted to examine whether an acute psychosocial stressor enhanced alcohol cue reactivity in non-treatment-seeking alcoholics. Methods Seventy-nine alcohol dependent individuals (39 women) randomly received either the Trier Social Stress Test or a no-stress control condition. Stress reactivity was measured with serum ACTH and cortisol, mean arterial blood pressure, and subjective distress. Immediately following the stress manipulation, participants held and sniffed a neutral cue then their preferred alcoholic beverage. Cue reactivity was measured by two subjective measures of craving following each cue. Additionally, general craving was assessed with the Alcohol Urge Questionnaire (AUQ) at the beginning and end of the laboratory procedure. Results The stress manipulation showed internal validity on all measures of stress reactivity. There was not a main effect of stress nor a stress x cue interaction on either cue reactivity measure. As expected, there was a main effect of cue (alcohol > neutral cue) on both measures of cue reactivity. General craving increased during the challenge, but not differently by stress group. Magnitude of stress reactivity was not associated with magnitude of cue reactivity, and all results were independent of gender. Conclusion In this well-controlled clinical laboratory study of non-treatment-seeking alcoholics, an acute psychological stressor did not make an alcohol cue a more potent urge-inducing stimulus, and stress had no effect on general alcohol craving.
Thomas, Suzanne E.; Randall, Patrick K.; Brady, Kathleen; See, Ronald E.; Drobes, David J.
Efficacy of metadoxine in the management of acute alcohol intoxication.
This randomized, open-label study evaluated the efficacy of 300 mg metadoxine (given intravenously) added to standard treatment compared with standard treatment alone in managing the physical and psychological signs of acute alcohol intoxication. Fifty-two acutely intoxicated patients were randomly assigned to one of two groups and followed during a 2-h period. Changes in clinical symptoms, degree of intoxication, and blood alcohol level were monitored. More patients receiving metadoxine in addition to standard therapy significantly improved by at least one degree of intoxication (one clinical category) compared with those receiving standard treatment alone (76.9% versus 42.3%, respectively). Metadoxine-treated patients also exhibited a significantly greater decrease in blood alcohol concentration compared with those receiving standard treatment alone (-105.4 +/- 61.5 mg/dl versus -60.1 +/- 38.6 mg/dl, respectively). Metadoxine improved the clinical signs of acute alcohol intoxication and accelerated alcohol clearance from the blood, thus supporting existing data. In contrast to previous data, these effects were concurrent but independent. No adverse effects were observed with metadoxine therapy. PMID:11921498
DĒaz MartĒnez, M C L R; DĒaz MartĒnez, A; Villamil Salcedo, V; Cruz Fuentes, C
The management of acute dental pain in the recovering alcoholic
Although there have been many advances in our understanding of the neurophysiology of pain, the management of acute pain continues to be a challenge. When the need arises to provide adequate and effective pain management for the recovering alcoholic, the problem becomes much more complex. The clinician must provide the patient with adequate analgesia without causing a relapse. In the
John E. Lindroth; M. Chris Herren; Donald A. Falace
The Acute Effect of Alcohol on Various Memory Processes
This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically
Mßrk Molnßr; Roland Boha; Balßzs Czigler; Zs¾fia Anna Gaßl
Inpatient management of acute alcohol withdrawal syndrome.
Alcohol withdrawal is a common condition encountered in the hospital setting after abrupt discontinuation of alcohol in an alcohol-dependent individual. Patients may present with mild symptoms of tremulousness and agitation or more severe symptoms including withdrawal seizures and delirium tremens. Management revolves around early identification of at-risk individuals and symptom assessment using a validated tool such as the revised Clinical Institute Withdrawal Assessment for Alcohol score. Benzodiazepines remain the mainstay of treatment and can be administered using a front-loading, fixed-dose, or symptom-triggered approach. Long-acting benzodiazepines such as chlordiazepoxide or diazepam are commonly used and may provide a smoother withdrawal than shorter-acting benzodiazepines, but there are no data to support superiority of one benzodiazepine over another. Elderly patients or those with significant liver disease may have increased accumulation and decreased clearance of the long-acting benzodiazepines, and lorazepam or oxazepam may be preferred in these patients. Patients with symptoms refractory to high doses of benzodiazepines may require addition of a rescue medication such as phenobarbital, propofol or dexmedetomidine. Anticonvulsants (carbamazepine, valproate, gabapentin) may have a role in the management of mild to moderate withdrawal. Other medications such as ?-antagonists or neuroleptics may offer additional benefit in select patients but should not be used a monotherapy. PMID:24781751
Perry, Elizabeth C
[Alcoholic hepatitis: clinical, laboratorial and histological study of 50 cases].
The clinical, laboratorial and histological aspects of 50 cases of alcoholic hepatitis were analysed, as well as the follow-up of 24 patients. The mean age of the 50 patients was 42,9 years (range: 25 to 65 years); 44 were males. The beginning of the symptomatology was insidious in great number of cases. The hepatomegaly was most habitual clinical signal (92% of cases). The jaundice was observed in 58% of the cases. Twenty six per cent of the patients had not manifestation of advanced hepatopaty at the moment of diagnosis. The most constant laboratorial alteration (except the increase of gama-glutamil-transpeptidase, dosed in rare cases) was the increase of SGOT (94%). Histological examination showed necrosis and inflammatory exudate in all cases; steatosis in 98%; Mallory bodies in 78%; fibrosis in 84%; cirrhosis in 44%. In the group of patients that came to the obit at the first internation, jaundice, digestive bleeding, encephalopathy, infection, leucocitosis and decreased prothrombin activity. The follow-up of 24 cases (3 months to 5 years) showed aggravation of illness and frequent evolution to cirrhosis in patient that maintained the alcohol ingestion. PMID:7181721
Gonńalves, C S; Pereira, F E; Boni, E S; Buaiz, V; Zanotti, W M; Zanandrķa, B
Acute viral hepatitis morbidity and mortality associated with hepatitis E virus infection: Uzbekistan surveillance data
BACKGROUND: In Uzbekistan, routine serologic testing has not been available to differentiate etiologies of acute viral hepatitis (AVH). To determine the age groups most affected by hepatitis E virus (HEV) during documented AVH epidemics, trends in AVH-associated mortality rate (MR) per 100,000 over a 15-year period and reported incidence of AVH over a 35-year period were examined. METHODS: Reported AVH
Makhmudkhan B Sharapov; Michael O Favorov; Tatiana L Yashina; Matthew S Brown; Gennady G Onischenko; Harold S Margolis; Terence L Chorba
Acute hepatitis B after autologous stem cell transplantation in a man previously infected by hepatitis B virus.
We report a case of acute hepatitis B after autologous stem cell transplantation (ASCT) in a patient with low-grade non-Hodgkin's lymphoma. At diagnosis of the hematological disease, the patient had the characteristic serology of a previous hepatitis B infection, being Ag HBs negative, hepatitis B virus core antibody positive (anti-HBC) and hepatitis B virus surface antibody weakly positive. He developed fatal hepatitis B after autologous stem cell transplantation, suggesting reactivation consequent to immunosuppression. PMID:10642815
Senecal, D; Pichon, E; Dubois, F; Delain, M; Linassier, C; Colombat, P
Hepatitis E in liver biopsies from patients with acute hepatitis of clinically unexplained origin.
Hepatitis E virus (HEV) is a small RNA virus and the infectious agent of hepatitis E that occurs worldwide either as epidemics in Asia caused by genotype 1 and 2 or as sporadic disease in industrialized countries induced by genotype 3 and 4. The frequency might be underestimated in central Europe as a cause of acute hepatitis. Therefore, we analyzed on liver biopsies, if cases of acute hepatitis with clinically unknown or obscure diagnosis were actually caused by the infection with HEV. We included 221 liver biopsies retrieved from the files of the institute of pathology during the years 2000 till 2010 that were taken from patients with acute hepatitis of obscure or doubtful diagnosis. From all biopsies RNA was extracted, prepared, and subjected to RT-PCR with specific primers. Amplified RNA was detected in 7 patients, sequenced and the genotype 3 could be determined in four of the seven of positive specimens from 221 samples. Histopathology of the biopsies revealed a classic acute hepatitis with cholestatic features and in some cases confluent necrosis in zone 3. Histology in a cohort of matched patients was less severe and showed more eosinophils. The analysis of the immune response by subtyping of liver infiltrating lymphocytes showed circumstantial evidence of adaptive immune reaction with CD 8 positive CTLs being the dominant lymphocyte population. In conclusion, in doubtful cases of acute hepatitis of unknown origin, HEV infection should be considered as etiology in central Europe. We demonstrate for the first time that the diagnosis can be made in paraffin-embedded liver biopsies reliably when no serum is available and also the genotype can be determined. The analysis of the immune response by subtyping of liver infiltrating lymphocytes indicates an adaptive mechanism suggesting in analogy with HAV, HBV and HCV that the virus itself is not cytopathic but liver damage is due to immune reaction. PMID:24379784
Drebber, Uta; Odenthal, Margarete; Aberle, Stephan W; Winkel, Nadine; Wedemeyer, Inga; Hemberger, Jutta; Holzmann, Heidemarie; Dienes, Hans-Peter
Acute and chronic ethanol on hepatic oxygen ethanol and lactate metabolism in cats.
The effects of increasing blood ethanol levels on hepatic hemodynamics and O2, ethanol, and lactate metabolism were studied in two groups of anesthetized cats: a control group and a group whose prior fluid intake contained 2, 4, then 8% ethanol for 24 days. Within each group, responses were compared in cats with acutely denervated and innervated livers. A hepatic venous long-circuit technique with an extracorporeal reservoir was used to allow hemodynamic measurements and repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cats' blood volume. Vmax for ethanol was 105 +/- 9 and 91 +/- 6 mumol.min-1 g liver-1 and Km was 136 +/- 18 and 168 +/- 24 microM for control and chronic alcohol groups, respectively. There was no stimulation of ethanol metabolism after chronic administration. O2 uptake by the liver was not altered during acute ethanol administration in any group and base-line O2 uptakes before acute administration of ethanol were not different between normal and chronic ethanol groups. No evidence for a hypermetabolic state induced by chronic ethanol administration was seen in innervated or acutely denervated livers. Oxidation of ethanol required 40-45% of normal O2 uptake; thus other oxidative processes must have been suppressed during ethanol metabolism. Hepatic lactate uptake remained unaltered when ethanol metabolism was less than 0.5 Vmax, but was suppressed on an equimolar basis with ethanol metabolism when ethanol metabolism rose to greater than 0.5 Vmax. Thus lactate metabolism is one process that can be suppressed to allow ethanol metabolism without additional O2 uptake by the liver. PMID:2316655
Greenway, C V; Lautt, W W
Elevated plasma interleukin-6 and increased severity and mortality in alcoholic hepatitis.
Recent studies in alcoholic hepatitis have proposed a role for the cytokine tumour necrosis factor-alpha (TNF-alpha) a mediator of endotoxic shock in sepsis. In this study plasma levels of the closely related cytokine interleukin-6 (IL-6) were assayed in 96 samples from 58 patients with severe alcoholic hepatitis, and 69 patients in control groups (21 normal, 10 alcoholic without liver disease, 10 inactive alcoholic cirrhosis, 18 chronic liver disease, 10 chronic renal failure). Plasma IL-6 levels were markedly elevated in patients with alcoholic hepatitis when compared with all control groups (P less than 0.001). IL-6 levels were higher in patients who died (P = 0.04) and correlated with the features of severe disease including: increased grade of encephalopathy, increased neutrophil count, increased prothrombin ratio, hypotension, increased serum creatinine and increased serum bilirubin. Surprisingly, no correlation was found between levels of plasma IL-6 and plasma TNF-alpha or endotoxin, or the presence of infection; an inverse correlation was found between plasma IL-6 and serum globulins. These findings provide further evidence that the IL-6/TNF cytokine system is activated in severe alcoholic hepatitis and may mediate hepatic or extra-hepatic tissue damage.
Sheron, N; Bird, G; Goka, J; Alexander, G; Williams, R
Hepatotherapeutic effect of Aloe vera in alcohol-induced hepatic damage.
There is a lack of reliable hepatotherapeutic drugs in modern medicine in the management of alcohol/drug-induced liver damage. Aloe vera extract has been used in folklore medicine for its medicinal values. This study evaluates the hepatotherapeutic activity of aqueous extract of Aloe vera gel in rats. Sprague-Dawley rats were divided into three groups; the negative control, positive control and the extract-treated groups. The negative control received only distilled water daily. The positive control received alcohol, while the extract-treated group received aqueous extract of Aloe vera and alcohol. Hepatotoxicity was induced in the positive control and extract-treated rats with alcohol. The hepatotherapeutic effect was evaluated by performing an assay of the serum total bilirubin, alkaline phosphatase, aspartate and alanine transaminases and liver histopathology. Alanine transaminase activities were comparable in all groups. Alcohol treatment alone significantly (p < 0.05) increased total serum bilirubin, alkaline phosphatase and aspartate transaminase activities. Alcohol-induced hepatic dysfunction was abrogated by Aloe vera extract. Histopathological examination revealed that alcohol induced hepatic damage. Aloe vera treatment maintained hepatic architecture similar to that seen in the control. This study shows that aqueous extract of Aloe vera gel is hepatotherapeutic and thus lends credence to the use of the plant in folklore medicine in the management of alcohol-induced hepatic dysfunction. PMID:22308658
Saka, W A; Akhigbe, R E; Ishola, O S; Ashamu, E A; Olayemi, O T; Adeleke, G E
Hypoxic hepatitis and acute liver failure in a patient with newly onset atrial fibrillation and diltiazem infusion.
Hypoxic hepatitis (HH) most commonly results from haemodynamic instability and disruption of hepatic flow. The vast majority of cases are caused by cardiac failure, respiratory failure and septic shock. We report a case of HH, acute liver failure, acute kidney failure and progressive thrombocytopenia that developed following a hypotensive episode in a patient treated with intravenous diltiazem for a newly developed atrial fibrillation (A-fib). The pre-existing liver diseases, including chronic alcohol use and liver congestion secondary to right heart dysfunction, might have predisposed the patient to the development of HH. The patient was given supportive treatment and experienced full recovery of both liver and kidney function. To our knowledge, this is the first reported case of HH that occurred following ventricular rate control for acute A-fib. For patients with underlying liver diseases, closer blood pressure monitoring is warranted during diltiazem infusion. PMID:24042208
Deng, Wu; Farricielli, Laurie
Acute Alcohol Use and Suicidal Behavior: A Review of the Literature
Background: Both acute and chronic use of alcohol are associated with suicidal behavior. However, the differing relationship of each component of alcohol use and possible causal mechanisms remain unclear. Methods: This article reviews and summarizes associations between acute alcohol consumption (with and without intoxication) and suicidal behavior (both completed suicide and suicide attempts) among adults 19 years and older, as
Cheryl J. Cherpitel; Guilherme L. G. Borges; Holly C. Wilcox
Acute Alcohol Effects on Inhibitory Control and Implicit Cognition: Implications for Loss of Control Over Drinking
Alcohol impairs inhibitory control, and it alters implicit alcohol cognitions including attentional bias and implicit associations. These effects are seen after doses of alcohol which do not lead to global impairments in cognitive performance. We review studies which demonstrate that the effects of alcohol on inhibitory control are associated with the ability of alcohol to prime alcohol-seeking behavior. We also hypothesize that alcohol-induced changes in implicit alcohol cognitions may partially mediate alcohol-induced priming of the motivation to drink. Based on contemporary theoretical models and conceptualizations of executive function, impulsivity, and the motivational salience of alcohol-related cues, we speculate on other aspects of cognition that may underlie alcoholÆs effects on alcohol seeking. Inconsistencies in existing research and priorities for future research are highlighted, including dose effects and the potential interactions between chronic heavy drinking and the acute effects of alcohol on these cognitive processes.
Field, Matt; Wiers, Reinout W.; Christiansen, Paul; Fillmore, Mark T.; Verster, Joris C.
Metabolic basis of ethanol-induced hepatic and pancreatic injury in hepatic alcohol dehydrogenase deficient deer mice.
Alcoholic liver disease (ALD) and alcoholic pancreatitis (AP) are major diseases causing high mortality and morbidity among chronic alcohol abusers. Neutral lipid accumulation (steatosis) is an early stage of ALD or AP and progresses to inflammation and other advanced stages of diseases in a subset of chronic alcohol abusers. However, the mechanisms of alcoholic steatosis leading to ALD and AP are not well understood. Chronic alcohol abuse impairs hepatic alcohol dehydrogenase (ADH, a major enzyme involved in ethanol oxidative metabolism) and facilitates nonoxidative metabolism of ethanol to fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol). These esters are implicated in the pathogenesis of various alcoholic diseases and shown to cause hepatocellular and pancreatitis-like injury. Ethanol exposure is known to increase synthesis of FAEEs by several-fold in the livers and pancreata of rats pretreated with hepatic ADH inhibitor. Therefore, studies were undertaken to evaluate hepatocellular and pancreatic injury in hepatic ADH-deficient (ADH(-)) deer mice versus ADH-normal (ADH(+)) deer mice fed ethanol (4% wt/vol) via Lieber-DeCarli liquid diet for 60 days. A significant mortality was found in ethanol-fed ADH(-) deer mice (11 out of 18) versus ADH(+) deer mice (1 out of 16); most of the deaths occurred during the first 2 weeks of ethanol exposure. The surviving animals, sacrificed at the end of 60th day, showed distinct changes in hepatic and pancreatic histology and several-fold increases in nonoxidative metabolism of ethanol in ethanol-fed ADH(-) versus ADH(+) deer mice. Extensive vacuolization with displacement or absence of nucleus in some hepatocytes, and significant increase in hepatic neutral lipids were found in ethanol-fed ADH(-) versus ADH(+) deer mice. Ultrastructural changes showed perinuclear space, edema, presence of apoptotic bodies and disintegration, and/or dilatation of endoplasmic reticulum (ER) in the pancreata of ethanol-fed ADH(-) deer mice. FAEE levels were significantly higher in ADH(-) versus ADH(+) deer mice, approximately four-fold increases in the livers and seven-fold increases in the pancreata. Ethyl esters of oleic, linoleic, and arachidonic acids were the major FAEEs detected in ethanol-fed groups. The role of FAEEs in pancreatic lysosomal fragility is reflected by higher activity of cathepsin B (five-fold) in ethanol-fed ADH(-) versus ADH(+) deer mice. Although the present studies clearly indicate a metabolic basis of ethanol-induced hepatic and pancreatic injury, detailed dose- and time-dependent toxicity studies in this ADH(-) deer mouse model could reveal further a better understanding of mechanism(s) of ethanol-induced hepatic and pancreatic injuries. PMID:17127137
Bhopale, Kamlesh K; Wu, Hai; Boor, Paul J; Popov, Vsevolod L; Ansari, G A S; Kaphalia, Bhupendra S
Systemic lupus erythematosus presenting as acute iceric hepatitis: a case report.
Liver involvement in systemic lupus erythematosus (SLE) is infrequent. The coexistence of SLE and autoimmune hepatitis is rare (1.3-1.7%). We report a case of a 27 year old female with no history of systemic illnesses or alcohol abuse that presented with acute hepatitis with jaundice, abdominal pain, and increased liver function tests. Viral markers were negative. ANA was strongly positive. Patient was suspected to have SLE but no definite diagnosis made. She remained asymptomatic for 9 years but then she had recurrence of hepatitis. She also presented with malar rash, arthritis, and proteinuria. At that time a liver biopsy showed autoimmune hepatitis. Other tests which confirmed SLE included a positive antidsDNA, positive antismith antibody and decreased complement levels. She was started on prednisone 40 mg with mild improvement of symptoms and transaminase values, but when azathioprine 100 mg was added a marked improvement in liver function tests was observed. After a year in azathioprine she remained with SLE in remission. To our knowledge this is the third reported case and the first in the Western Hemisphere of jaundice as the initial presentation of SLE. PMID:19227719
Rodriguez, Vanessa E; Costas, Pablo
White cell count and platelet count associate with histological alcoholic hepatitis in jaundiced harmful drinkers
Background Patients with suspected alcoholic hepatitis and a Discriminant Function ?32 underwent liver biopsy to confirm the diagnosis. Of these (n?=?58), 43 had histological features of alcoholic hepatitis and 15 (25%) did not. We aimed to determine the laboratory features that differentiated those patients with a histological diagnosis of alcoholic hepatitis from those without, and assess potential clinical utility. Methods Laboratory investigations at presentation for each of the histologically confirmed cases of alcoholic hepatitis (n?=?43) were compared to those without (n?=?15) to determine whether there were differences between the two groups. Univariate analysis was by Mann Whitney U Test and Multivariate analysis was by a stepwise approach. Results White cell count (16.2?▒?10.5 v 6.9?▒?3.5 (ū?109/L); p?=?0.0001) and platelet count (178?▒?81 v 98.4?▒?43 (ū?109/L); p?=?0.0005) were higher in the patients with histological features of alcoholic hepatitis than in those without. The area under the ROC curve for AH diagnosis was estimated to be 0.83 (0.73, 0.94) and 0.81 (0.69, 0.93) for white cell count and platelet count respectively. Conclusions Clinicians cannot accurately differentiate patients with or without alcoholic hepatitis without liver biopsy. This is critically important when deciding on specific therapies such as corticosteroids or when interpreting data from future trials in which biopsy is not mandated. In situations where liver biopsy is unsuitable or unavailable the white cell and platelet counts can be used to determine the likelihood of histological alcoholic hepatitis and guide treatment.
Management practices of hepatitis C virus infected alcoholic hepatitis patients: A survey of physicians
AIM: To survey gastroenterologists and hepatologists regarding their current views on treating hepatitis C virus (HCV) infected alcoholic hepatitis (AH) patients. METHODS: A sixteen item questionnaire was electronically mailed to gastroenterologists and hepatologists. A reminder was sent after 2 mo to increase the response rate. Participation of respondents was confidential. Accessing secured web site to respond to the questionnaire was considered as informed consent. Responses received on the secured website were downloaded in an excel sheet for data analysis. RESULTS: Analyzing 416 responses to 1556 (27% response rate) emails, 57% respondents (56% gastroenterologists) reported HCV prevalence > 20% amongst AH patients. Sixty nine percent often treated AH and 46% preferred corticosteroids (CS). Proportion of respondents with consensus (75% or more respondents agreeing on question) on specific management of HCV infected AH were: routine HCV testing (94%), HCV not changing response to CS (80%) or pentoxifylline (91%), no change in approach to treating HCV infected AH (75%). None of respondent variables: age, specialty, annual number of patients seen, and HCV prevalence could predict respondent to be in consensus on any of or all 4 questions. Further, only 4% would choose CS for treating HCV infected AH as opposed to 47% while treating HCV negative AH. CONCLUSION: Gastroenterologists and hepatologists believe that AH patients be routinely checked for HCV. However, there is lack of consensus on choice of drug for treatment and outcome of HCV positive AH patients. Studies are needed to develop guidelines for management of HCV infected AH patients.
Singal, Ashwani K; Salameh, Habeeb; Singal, Anjna; Jampana, Sarat C; Freeman, Daniel H; Anderson, Karl E; Brunder, Don
Serologic Classification of Acute Viral Hepatitis at San Lazaro Hospital, Manila, Philippines.
National Technical Information Service (NTIS)
Sixty-four out of 189 jaundiced patients at San Lazaro Hospital were defined as acute viral hepatitis cases. Of this number, 22 (33.4%) were positive for hepatitis A markers while 26 (40.6%) were positive for hepatitis B markers. Hepatitis D infection acc...
N. E. Sy P. S. Macalagay G. P. Paulino V. D. Fallarme R. S. Reyes
[Acute alcoholic intoxication in children in Vojvodina].
The aim of this work was to investigate the frequency and characteristics of acute ethanol poisoning in children in the territory of the Socialist Autonomous Province of Voivodina. In a retrospective study histories of poisoned children aged 0-15 years, who were hospitalized in all eleven stationary centres in Voivodina during 1985/86, were analysed. From 795 children, 52 were poisoned with ethanol (6.54%). With the exception of Novi Knezevac, where only eight cases of poisoning were recorded during the two-year period, the frequency of ethanol poisoning showed major regional differences varying from 3.03% in Zrenjanin to 11.45% in Subotica. Poisoning among boys was significantly more frequent than among girls, especially with ethanol. The average age of children poisoned with ethanol was 8.4 years i.e. almost twice that of children poisoned with other substances. The children's age and circumstances of ethanol poisoning point to the absence and failure of preventive measures. PMID:2803010
Roncevi?, N; Konstantinidis, G; Stevanovi?, V
Factors associated with fulminant liver failure during an outbreak among injection drug users with acute hepatitis B.
Death related to acute hepatitis B occurs in approximately 1% of patients. We investigated an outbreak of hepatitis B virus (HBV) infections among injection drug users (IDUs) resulting in several deaths. We conducted a case-control study of fulminant (case patients) and nonfulminant (control patients) HBV infections. We directly sequenced the entire HBV genome from fulminant and nonfulminant cases. From October 1998 to July 2000, 21 acute HBV infections, including 10 fulminant hepatitis B cases, were identified. The median age was 30 (range, 18-49) years, 12 (57%) were female, 20 (95%) were American Indians, and 20 (95%) reported injecting illicit drugs. All patients with fulminant hepatitis B died (case-fatality rate = 47.6%). Case patients (n = 5) and control patients (n = 9) were similar with respect to age, sex, race, and hepatitis C virus serostatus. All case patients used acetaminophen during their illness compared with 44% of control patients (P =.08). Compared with control patients, case patients lost more weight in the 6 months before illness (P =.04); during their illness, they used more alcohol (P =.03) and methamphetamine (P =.04). All 9 isolates sequenced were genotype D, shared 99.7% homology, and included mutations previously described in association with fulminant hepatitis B. In conclusion, a high prevalence of exposure to factors potentiating hepatic damage with acute hepatitis B contributed to the outbreak's high mortality rate; mutations present in the outbreak strain might also have been a factor. Improved vaccination coverage among IDUs has the potential to prevent similar outbreaks in the future. PMID:15382123
Garfein, Richard S; Bower, William A; Loney, Cherry M; Hutin, Yvan J F; Xia, Guo-Liang; Jawanda, Jaspaul; Groom, Amy V; Nainan, Omana V; Murphy, James S; Bell, Beth P
Acute autoimmune hepatitis mimicking metastatic liver disease: A case report.
We report progressive painless jaundice in a 39 year old female with a suspicion of metastatic liver disease on ultrasound and computed tomography scan of the abdomen. Although the most frequent liver lesions are liver metastasis because of dual blood supply of the liver and the impact of hormones, the index case proved to have acute autoimmune hepatitis (AIH) after liver biopsy was undertaken. AIH, an unresolving inflammation of liver, occurs predominantly among females worldwide. It may present acutely and even fulminant hepatitis has been described. The index case had a dramatic response to steroid treatment with total recovery and complete resolution of liver lesions. She is clinically fine and has been regularly attending our clinic for the last year. To our knowledge from a Medline search, this is the first report where AIH was seen to mimic metastatic liver disease. PMID:22855700
Masoodi, Ibrahim; Alsayari, Khalid
Acute autoimmune hepatitis mimicking metastatic liver disease: A case report
We report progressive painless jaundice in a 39 year old female with a suspicion of metastatic liver disease on ultrasound and computed tomography scan of the abdomen. Although the most frequent liver lesions are liver metastasis because of dual blood supply of the liver and the impact of hormones, the index case proved to have acute autoimmune hepatitis (AIH) after liver biopsy was undertaken. AIH, an unresolving inflammation of liver, occurs predominantly among females worldwide. It may present acutely and even fulminant hepatitis has been described. The index case had a dramatic response to steroid treatment with total recovery and complete resolution of liver lesions. She is clinically fine and has been regularly attending our clinic for the last year. To our knowledge from a Medline search, this is the first report where AIH was seen to mimic metastatic liver disease.
Masoodi, Ibrahim; Alsayari, Khalid
Single-dose kinetics of primidone in acute viral hepatitis
The pharmacokinetics of primidone (PRM) after oral administration of a single 500 mg dose was studied in 7 patients with acute viral hepatitis and 7 healthy control subjects. The elimination half-life and the apparent clearance of unchanged PRM in the patients were 18.0▒3.1 h and 42▒14 mlĘh-1Ękg-1, respectively (mean ▒ SD) and did not differ significantly from the values in
F. Pisani; E. Perucca; G. Primerano; A. A. D'Agostino; R. M. Petrelli; A. Fazio; G. Oteri; R. Di Perri
Renal failure in otherwise uncomplicated acute viral hepatitis
Twelve patients with otherwise uncomplicated acute viral hepatitis (two were HBsAg-positive) developed renal failure. Apart from dehydration due to repeated vomiting in one patient, no factor responsible for precipitating renal failure could be identified. The clinical course was characterised by renal failure with plasma urea concentrations reaching maximum values of 26-69 mmol\\/l (175-416 mg\\/100 ml). Ten patients needed dialysis for
S P Wilkinson; M H Davies; B Portmann; R Williams
Hepatitis E virus in patients with acute severe liver injury
AIM: To examine the incidence of hepatitis E (HepE) in individuals with acute liver injury severe enough to warrant treatment at a transplant unit. METHODS: Hepatitis E virus (HEV) is an emerging pathogen in developed countries causing severe illness, particularly in immunocompromised patients or those with underlying chronic liver disease. HepE infection is often under diagnosed, as clinicians can be reluctant to test patients who have not travelled to regions traditionally considered hyperendemic for HepE. There are few data regarding the significance of HEV in patients with very severe acute liver injury in developed countries. Eighty patients with acute severe liver injury attending the Scottish Liver Transplant unit were tested for HEV and anti-HEV IgG and IgM. Severe acute liver injury was defined as a sudden deterioration in liver function confirmed by abnormal liver function tests and coagulopathy or presence of hepatic encephalopathy. Eighty percent of these patients were diagnosed with paracetomol overdose. No patients had a history of chronic or decompensated chronic liver disease at time of sampling. IgG positive samples were quantified against the World Health Organization anti-HEV IgG standard. Samples were screened for HEV viral RNA by quantitative reverse transcription polymerase chain reaction. RESULTS: Four cases of hepatitis E were identified. Three of the four cases were only diagnosed on retrospective testing and were initially erroneously ascribed to drug-induced liver injury and decompensated chronic liver disease, with the cause of the decompensation uncertain. One case was caused by HEV genotype 1 in a traveller returning from Asia, the other three were autochthonous and diagnosed on retrospective testing. In two of these cases (where RNA was detected) HEV was found to be genotype 3, the most prevalent genotype in developed countries. Three patients survived, two of whom had been misdiagnosed as having drug induced liver injury. The fourth patient died from sepsis and liver failure precipitated as a result of hepatitis E infection and previously undiagnosed cirrhosis. Histopathology data to date is limited to mainly that seen for endemic HepE. All patients, with the exception of patient 1, demonstrated characteristics of HepE infection, as seen in previously described locally acquired cases. CONCLUSION: In patients with acute severe liver injury, HEV testing should be part of the initial diagnostic investigation algorithm irrespective of suspected initial diagnosis, age or travel history.
Crossan, Claire Louise; Simpson, Kenneth J; Craig, Darren G; Bellamy, Christopher; Davidson, Janice; Dalton, Harry R; Scobie, Linda
IgM-antibody response to the hepatitis B core antigen in acute and chronic hepatitis B.
A solid phase M-antibody capture radioimmunoassay (MACRIA) and a serum fractionation method were used to quantitate the IgM response to the hepatitis B core antigen (IgM anti-HBc) in acute and chronic hepatitis B infections. Antibody to the core antigen was predominantly of the IgM class during the acute phase of hepatitis B. Resolving acute infections remained positive by MACRIA, but at decreasing levels, for as long as 6 months. IgM anti-HBc persisted in HBsAg carriers but at levels very much lower than seen in acute infections. There was no correlation of IgM anti-HBc with severity of chronic liver disease in carriers. Measurement of IgM anti-HBc by MACRIA enabled accurate identification of acute hepatitis B on single serum specimens.
Tedder, R. S.; Wilson-Croome, R.
Alcohol consumption among patients with hepatitis B infection in northern Portugal considering gender and hepatitis B virus genotype differences.
Alcohol abuse is an important public health problem. In Portugal with a population of 10 millions of inhabitants, there are around 10% of alcoholics or excessive alcohol drinkers and 1% of chronically infected patients with hepatitis B virus (HBV). To examine the characteristics of patients with higher levels of alcohol consumption and to investigate the association between alcohol consumption and liver damage a total of 298 chronically infected individuals, with HBV genotyped and submitted to liver biopsy, were classified with Child's grading and separated by habits of alcohol intake, less and greater than 20g/day. No significant differences were observed about genotype but genotypes A and D were predominant in both of them. A higher percentage of males (P<.001) were observed in the group with alcohol intake above 20g/day, as well a lower proportion of patients with HBeAg negativity (P< or =.035). In this group, biochemistry parameters, such as alanine aminotransferase (P=.006), aspartate aminotransferase (P=.001), gamma-glutamyl transferase (P<.001) were elevated in a significantly higher proportion than in the other group. The analysis of hematological parameters showed significantly lower values of platelets (P=.042) and mean corpuscular volume (P<.001) and significantly higher values of prothrombin time (P<.001) in the group with higher levels of alcohol consumption. The characteristics of biopsy (P<.001) and Child-Phug's classification (P=.002) revealed more severe results in this group. Logistic regression showed a positive association between liver damage and alcohol intake, increasing with age. In female patients, a strong positive association between alcohol intake and liver damage was also found (odds ratio: 9.379; 95% confidence interval: 0.859-468.422; P = .037); however, the most severe cases were only observed in women older than 45 years. In patients with HBV infection, alcohol is associated with a more severe liver disease. No evidence was found concerning association with HBV genotype. PMID:20116194
Mota, Ana; Guedes, Fßtima; Areias, Jorge; Pinho, Luciana; Cardoso, Margarida Fonseca
The ABCs of viral hepatitis that define biomarker signatures of acute viral hepatitis.
Viral hepatitis is the leading cause of liver disease worldwide and can be caused by several agents, including hepatitis A (HAV), B (HBV), and C (HCV) virus. We employed multiplexed protein immune assays to identify biomarker signatures of viral hepatitis in order to define unique and common responses for three different acute viral infections of the liver. We performed multianalyte profiling, measuring the concentrations of 182 serum proteins obtained from acute HAV- (18), HBV- (18), and HCV-infected (28) individuals, recruited as part of a hospital-based surveillance program in Cairo, Egypt. Virus-specific biomarker signatures were identified and validation was performed using a unique patient population. A core signature of 46 plasma proteins was commonly modulated in all three infections, as compared to healthy controls. Principle component analysis (PCA) revealed a host response based upon 34 proteins, which could distinguish HCV patients from HAV- and HBV-infected individuals or healthy controls. When HAV and HBV groups were compared directly, 34 differentially expressed serum proteins allowed the separation of these two patient groups. A validation study was performed on an additional 111 patients, confirming the relevance of our initial findings, and defining the 17 analytes that reproducibly segregated the patient populations. Conclusions: This combined discovery and biomarker validation approach revealed a previously unrecognized virus-specific induction of host proteins. The identification of hepatitis virus specific signatures provides a foundation for functional studies and the identification of potential correlates of viral clearance. PMID:24500966
Duffy, Darragh; Mamdouh, Rasha; Laird, Melissa; Soneson, Charlotte; Le Fouler, Lenaig; El-Daly, Ma'; Casrouge, Armanda; Decalf, Jķrķmie; Abbas, Amal; Eldin, Noha Sharaf; Fontes, Magnus; Abdel-Hamid, Mohamed; Mohamed, Mostafa K; Rafik, Mona; Fontanet, Arnaud; Albert, Matthew L
[Two cases of acute hepatitis associated with Q fever].
Q fever which is caused by Coxiella burnetii, is a worldwide zoonosis. Many species of wild and domestic mammals, birds, and arthropods, are reservoirs of C.burnetii in nature, however farm animals are the most frequent sources of human infection. The most frequent way of transmission is by inhalation of contaminated aerosols. The clinical presentation of Q fever is polymorphic and nonspecific. Q fever may present as acute or chronic disease. In acute cases, the most common clinical syndromes are selflimited febrile illness, granulomatous hepatitis, and pneumonia, but it can also be asymptomatic. Fever with hepatitis associated with Q fever has rarely been described in the literature. Herein we report two cases of C.burnetii hepatitis presented with jaundice. In May 2011, two male cases, who inhabited in Malkara village of Tekirdag province (located at Trace region of Turkey), were admitted to the hospital with the complaints of persistent high grade fever, chills and sweats, icterus, disseminated myalgia and headache. Physical examination revealed fever, icterus and the patient appeared to be mildly ill but had no localizing signs of infection. Radiological findings of the patients were in normal limits. Laboratory findings revealed leukocytosis, increased hepatic and cholestatic enzyme levels, and moderate hyperbilirubinemia- mainly direct bilirubin, whereas serum C-reactive protein and erythrocyte sedimentation rate were found normal. Blood and urine cultures of the patients yielded no bacterial growth. Serological markers for acute viral hepatitis, citomegalovirus and Epstein-Barr virus infections, brucellosis, salmonellosis, toxoplasmosis and leptospirosis were found negative. Acute Q fever diagnosis of the cases were based on the positive results obtained by C.burnetii Phase II IgM and IgG ELISA (Vircell SL, Spain) test, and the serological diagnosis were confirmed by Phase I and II immunofluorescence (Vircell SL, Spain) method. Both cases were treated with doxycycline for 14 days and became afebrile within four days. These cases were presented to emphasize that C.burnetii infection should be considered in the differential diagnosis of patients with fever and elevated serum transaminase levels, irrespective of the presence of abdominal pain and exposure to potentially infected animals. PMID:22951661
Ye?ilyurt, Murat; K?l?ń, Selńuk; G³rsoy, Bensu; Celebi, Bekir; Yerer, Mehmet
Alcohol and trauma: The impact of acute and chronic alcohol abuse on injury severity and death in a trauma population
Study objectives: To explore possible impact of acute and chronic alcohol abuse on injury severity and mortality in male and female trauma patients. Design: A prospective cohort study. Setting: Regional Level 1 trauma center in Seattle, Washington, USA. Participants: 2195 men and 664 women 18 years or older, admitted with blunt or penetrating trauma. Main results: The effect of alcohol
Odd Nilssen; Richard K. Ries; Fredrick P. Rivara; James G. Gurney; Gregory J. Jurkovich; Harborview Injury
Biological characterization of acute infection with ground squirrel hepatitis virus.
Ground squirrel hepatitis virus (GSHV) is a small DNA virus, structurally and antigenically related to the human hepatitis B virus, which occurs naturally among certain wild populations of ground squirrels (P. L. Marion et al., Proc. Natl. Acad. Sci. U.S.A. 77:2941-2945, 1980). Serum from naturally infected animals was used to transmit GSHV in the laboratory by parenteral inoculation of susceptible squirrels. Sixty percent of recipient animals developed viral surface antigenemia after a latent period of 2 to 3 months; three of these animals have remained viremic for over 9 months. Like hepatitis B virus, GSHV demonstrates marked hepatotropism, with viral DNA detected in significant quantities only in the liver, where an average of 6 X 10(2) to 6 X 10(3) viral DNA molecules per cell were found by molecular hybridization. However, histological signs of liver injury after acute infection are minimal. In contrast to infection of its natural host, parenteral administration of GSHV to rats, mice, guinea pigs, and hamsters did not result in demonstrable antigenemia, suggesting that the host range of GSHV, like that of hepatitis B virus, is narrow. Images
Ganem, D; Weiser, B; Barchuk, A; Brown, R J; Varmus, H E
Acute renal insufficiency and toxic hepatitis following scorpions sting.
Scorpion sting is a huge medical problem in countries of South America, Arabian Peninsula and Africa. In countries of Mediterranean region, where Bosnia and Herzegovina belongs, this problem is sporadic. Following the sting of very poisonous red scorpions, death may occur inside of 48 hours by reason of cardiac arrest and acute renal insufficiency (ARI). In our work we represent a case of 54-years old man. In his case, ARI and toxic hepatitis developed inside of 24 hours after the scorpion sting. Applied conservative therapy was not sufficient enough to solve ARI, so patient needed haemodialysis. With intensive conservative therapy and haemodialysis applied every other day, ARI and toxic hepatitis were solved within 25 days. After that, patient was released from hospital for ambulant treatment. PMID:17629151
Krkic-Dautovic, Sajma; Begovic, Begler
Acute hepatitis A virus infections in British Gurkha soldiers.
Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections are endemic in most developing countries, including Nepal and Afghanistan, and may cause outbreaks in military personnel. Previously, more than 99% of new British Gurkha recruits were already immune to HAV because of prior infection, but this may be declining due to improved living conditions in their countries of origin. Acute HAV infections have occurred in Gurkha soldiers serving in Afghanistan, which made them unfit for duty for 2-3 months. In one case, early serological diagnosis was impeded by IgM results against both HAV and HEV that were caused by cross-reactivity or persistence from a previous infection. These cases have led to a policy change whereby all Gurkha recruits are now tested for previous HAV infection and if negative they are offered vaccination. Meanwhile, HEV infection remains a significant threat in Nepal and Afghanistan with low levels of background immunity and no commercially available vaccine. PMID:23720504
Green, Chris A; Ross, D A; Bailey, M S
Hepatic cryoablation-induced acute lung injury: histopathologic findings.
We have previously shown that hepatic cryoablation (cryo), but not partial hepatectomy, induces a systemic inflammatory response, with distant organ injury and overproduction of NF-kappaB-dependent cytokines. Serum tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) levels are markedly increased 1 h and beyond after cryo compared with partial hepatectomy where no elevation occurs. NF-kappaB activation (by electrophoretic mobility shift assay) is strikingly increased in the noncryo liver (but not in the lung) at 30 min and in both the liver and lung tissue 1 h after cryo, returning to the baseline by 2 h and beyond. The current study investigated the histopathologic changes associated with cryoablation-induced acute lung injury. Animals underwent 35% hepatic resection or a similar volume hepatic cryo and were sacrificed at 1, 2, 6, and 24 h. Pulmonary histologic features were assessed using hematoxylin and eosin and immunoperoxidase staining with a macrophage-specific antibody (anti-lysozyme, 1:200 dilution, Dako, Carpinteria, CA). The following features were graded semiquantitatively (0-3): perivascular lymphoid cuffs, airspace edema and hemorrhage, margination of neutrophils within pulmonary vasculature, and the presence of macrophages with foamy cytoplasm in the pulmonary interstitium. Hepatic resection (n = 21) resulted in slight perivascular edema at 1, 2, 6, and 24 h post-resection, but there were no other significant changes. Pulmonary findings after hepatic cryo (n = 22) included prominent perivascular lymphoid cuffs 1 and 2 h following hepatic injury that were not present at any other time point (P 0.01). Marginating PMNs and foamy macrophages were more common after cryo at all time points (P<0.05, cryo vs resection). Severe lung injury, as evidenced by airspace edema and parenchymal hemorrhage, was present in four of six (67%) animals at 24 h (P 0.03). In follow-up studies immediate resection (n = 15) of the cryo-treated liver prior to thawing prevented the pulmonary changes. The findings of pulmonary perivascular interstitial macrophages 2 h following hepatic cryo suggests that hepatic cytokine production may induce downstream recruitment of pulmonary macrophages, which may contribute to subsequent severe lung injury. This study suggests that a soluble mediator from direct liver injury leads to neutrophilic lung inflammation and this is associated with the thawing phase of cryoablation. PMID:11120627
Washington, K; Debelak, J P; Gobbell, C; Sztipanovits, D R; Shyr, Y; Olson, S; Chapman, W C
The acute effect of alcohol on decision making in social drinkers
RationaleĀĀMany studies have reported the long-term adverse effects of alcohol on executive cognitive function in chronic alcohol abusers,\\u000a yet little research has investigated the acute effects of alcohol in social drinkers. Studies on acute effects report alcohol-induced\\u000a deficits on tasks that require executive cognitive processes, with alcohol acting to increase preservative errors and reduce\\u000a planning.\\u000a \\u000a \\u000a \\u000a AimĀĀThe present investigation examines the
S. George; R. D. Rogers; T. Duka
Pseudo-Budd-Chiari Syndrome: decompensated alcoholic liver disease mimicking hepatic venous outflow obstruction.
Three patients with rapid onset decompensated liver disease who were referred to our hospital with presumed Budd-Chiari syndrome are described. This diagnosis was based on marked hepatomegaly, caudate lobe hypertrophy and failure to visualize hepatic veins by Doppler-ultrasound examination. Detailed history, biochemistry, and histology were, however, highly suggestive of alcoholic liver cirrhosis with steatohepatitis-induced hepatomegaly. On angiographic examination narrowed but patent hepatic veins were demonstrated in 2 patients. A third patient died before further work-up could be performed; autopsy showed patent hepatic veins. These cases show that the radiological diagnosis of Budd-Chiari syndrome due to hepatic vein obstruction can be false positive and that suspected hepatic vein occlusion on Doppler-ultrasound should be confirmed by angiographic studies and on liver histology. PMID:12063996
Janssen, Harry L A; Tan, Adriaan C I T L; Tilanus, Hugo W; Metselaar, Herold J; Zondervan, Pieter E; Schalm, Solko W
Recovery and Sequence Analysis of Hepatitis A Virus from Springwater Implicated in an Outbreak of Acute Viral Hepatitis?
An outbreak of acute hepatitis A virus in North Carolina was linked to drinking water from a contaminated shallow spring by phylogenetic analysis of hepatitis A virus (HAV) genomic sequences. Detection of HAV and fecal indicators in the water provided useful and timely information to assist with public health prevention and control measures.
Tallon, Lindsay A.; Love, David C.; Moore, Zack S.; Sobsey, Mark D.
Recovery and sequence analysis of hepatitis a virus from springwater implicated in an outbreak of acute viral hepatitis.
An outbreak of acute hepatitis A virus in North Carolina was linked to drinking water from a contaminated shallow spring by phylogenetic analysis of hepatitis A virus (HAV) genomic sequences. Detection of HAV and fecal indicators in the water provided useful and timely information to assist with public health prevention and control measures. PMID:18708522
Tallon, Lindsay A; Love, David C; Moore, Zack S; Sobsey, Mark D
Genetic analysis of hepatitis A virus strains recovered from the environment and from patients with acute hepatitis
The molecular epidemiology of hepatitis A virus (HAV) was studied by analysing HAV strains recovered from environmental water samples over a 7 year period and strains recovered from patients with acute hepatitis over a 5 year period. A total of 54 samples of raw domestic sewage and 66 samples of river water were collected. HAV particles were concentrated and detected
Sonia Pina; Maria Buti; Rosend Jardi; Pilar Clemente-Casares; Joan Jofre; Rosina Girones
Acute hepatic injury with atorvastatin: An unusual occurrence
Atorvastatin, a commonly used and well-tolerated hypolipidemic drug, belongs to the class of statins or hydroxymethylglutaryl-coenzyme A reductase inhibitors. Use of atorvastatin may be associated with minor asymptomatic elevations in serum aminotransferases, but clinically significant hepatotoxicity is usually infrequent. Here we present a case of self-limiting clinically apparent acute hepatic injury attributable to atorvastatin occurring at recommended daily dose of 20 mg once a day. This case was postulated to be an unusual idiosyncratic reaction of the drug.
Vishwakarma, Pinki; Nehra, Rajiv; Kumar, Alok
Alcohol Pretreatment Increases Hepatic and Pulmonary Injury in Experimental Pancreatitis
Background: Systemic complications including pancreatitis-associated lung injury (PALI) are critical factors that determine the outcome of severe necrotizing pancreatitis (SNP). The aim of the present study was to evaluate the role of chronic alcohol exposure on the development of PALI. Methods: 48 rats were fed either a Lieber deCarli control or alcohol diet for 6 weeks. After completion, SNP was
Lutz Schneider; Matthias Pietschmann; Werner Hartwig; Thilo Hackert; Sara S. Marcos; Thomas Longerich; Martha-Maria Gebhard; Markus W. B³chler; Jens Werner
Hepatic intestinal uptake and release of catecholamines in alcoholic cirrhosis. Evidence of enhanced hepatic intestinal sympathetic nervous activity.
Hepatic intestinal and whole body plasma clearance and appearance of noradrenaline (NA) was quantified in patients with alcoholic cirrhosis (n = 12) and in controls (n = 6). As NA may be released as well as removed in the same vascular bed, infusion of tritium labelled NA (3H-NA) was carried out during hepatic vein catheterisation in order to determine both flux rates. In alcoholic cirrhosis plasma concentrations of endogenous NA and adrenaline (A) were significantly above control values (NA: median 2.4 v 1.7 nmol/l, p less than 0.02; A: 0.38 v 0.19 nmol/l, p less than 0.01). Whole body clearance of 3H-NA equal in the two groups (1.6 v 1.7 l/min, ns), while as the overall appearance rate of NA was significantly higher in alcoholic cirrhosis (4.2 v 2.6 nmol/min, p less than 0.02) indicating an enhanced sympathoadrenal activity in this group. The hepatic intestinal clearances of A, NA, and 3H-NA were not significantly different in patients and controls, but the estimated hepatic intestinal spillover rate of NA was 0.24 nmol/min in patients as compared with 0.0 nmol/min in controls (p less than 0.02). As a result of portosystemic shunting in cirrhosis the present estimation of NA spillover represents a minimum value. Our results indicate that the augmented circulating catecholamines in cirrhosis do not result from diminished removal but are contributed to from increased sympathetic nervous activity in the hepatic intestinal area (enhanced mesenteric sympathetic nervous activity).
Henriksen, J H; Ring-Larsen, H; Christensen, N J
Acute hepatitis induced by an Aloe vera preparation: A case report
AIM: Aloe vera, plant extracts of Aloe barbadensis miller, is widely used in phytomedicine. The first case of acute hepatitis due to this compound was described. METHODS: Description of a clinical case. RESULTS: Hepatitis in a 57-year old female could be linked to the ingestion of Aloe barbadensis miller compounds. The patients hepatitis resolved completely after discontinuing this medication. CONCLUSION:
Christian Rabe; Annemarie Musch; Peter Schirmacher; Wolfgang Kruis; Robert Hoffmann
Acute Sporadic Hepatitis E in Children Living in Cairo, Egypt. (Reannouncement with New Availability Information).
National Technical Information Service (NTIS)
Seventy-three pediatric patients with acute hepatitis and 19 control patients without liver disease living in Cairo, Egypt, were evaluated with a newly developed Western blot assay for IgM antibody to hepatitis E virus (IgM anti-HEV). The mean age of acut...
K. C. Hyams M. C. McCarthy M. Kaur M. A. Purdy D. W. Bradley
Blood flow velocity, erythrocyte deformability and hepatic enzymes in heavy alcohol drinkers
Significantly decreased blood flow velocity in cerebral arteries, as well as decreased erythrocyte deformability, was found in heavy alcohol drinkers (Gdovinovß 2002). The aim of this study was to determine if there is any correlation between the two. At the same time, the correlation between blood flow velocity and hepatic enzymes was also studied. The study group comprised 30 male
Zuzana Gdovinovß
Pathogenesis of hepatic steatosis: The link between hypercortisolism and non-alcoholic fatty liver disease
Based on the available literature, non alcoholic fatty liver disease or generally speaking, hepatic steatosis, is more frequent among people with diabetes and obesity, and is almost universally present amongst morbidly obese diabetic patients. Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world, with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation. Previous data report that only 20% of patients with CushingÆs syndrome have hepatic steatosis. Aiming at clarifying the reasons whereby patients suffering from CushingÆs syndrome - a condition characterized by profound metabolic changes - present low prevalence of hepatic steatosis, the Authors reviewed the current concepts on the link between hypercortisolism and obesity/metabolic syndrome. They hypothesize that this low prevalence of fat accumulation in the liver of patients with CushingÆs syndrome could result from the inhibition of the so-called low-grade chronic-inflammation, mainly mediated by Interleukin 6, due to an excess of cortisol, a hormone characterized by an anti-inflammatory effect. The CushingÆs syndrome, speculatively considered as an in vivo model of the hepatic steatosis, could also help clarify the mechanisms of non alcoholic fatty liver disease.
Tarantino, Giovanni; Finelli, Carmine
Investigation of SEN Virus Infection in Patients with Cryptogenic Acute Liver Failure, Hepatitis?Associated Aplastic Anemia, or Acute and Chronic Non¢A¢E Hepatitis
SEN virus (SENV) has been tentatively linked to transfusion-associated non-A-E hepatitis. We investigated SENV's role in unexplained hepatitis in other settings. Polymerase chain reaction amplification was used to detect 2 SENV variants (SENV-D and SENV-H) in 1706 patients and control subjects. SENV was detected in 54 (22%) of 248 patients with acute or chronic non-A-E hepatitis, 9 (35%) of 26
Takeji Umemura; Eiji Tanaka; George Ostapowicz; Stefan Heringlake; Koji Orii; Angelos Hatzakis; Kendo Kiyosawa
Acute viral hepatitis morbidity and mortality associated with hepatitis E virus infection: Uzbekistan surveillance data
Background In Uzbekistan, routine serologic testing has not been available to differentiate etiologies of acute viral hepatitis (AVH). To determine the age groups most affected by hepatitis E virus (HEV) during documented AVH epidemics, trends in AVH-associated mortality rate (MR) per 100,000 over a 15-year period and reported incidence of AVH over a 35-year period were examined. Methods Reported AVH incidence data from 1971 to 2005 and AVH-associated mortality data from 1981 to 1995 were examined. Serologic markers for infection with hepatitis viruses A, B, D, and E were determined from a sample of hospitalized patients with AVH from an epidemic period (1987) and from a sample of pregnant women with AVH from a non-epidemic period (1992). Results Two multi-year AVH outbreaks were identified: one during 1975¢1976, and one during 1985¢1987. During 1985¢1987, AVH-associated MRs were 12.3¢17.8 per 100,000 for the general population. Highest AVH-associated MRs occurred among children in the first 3 years of life (40¢190 per 100,000) and among women aged 20¢29 (15¢21 per 100,000). During 1988¢1995 when reported AVH morbidity was much lower in the general population, AVH-associated MRs were markedly lower among these same age groups. In 1988, AVH-associated MRs were higher in rural (21 per 100,000) than in urban (8 per 100,000) populations (RR 2.6; 95% CI 1.16¢5.93; p < 0.05). Serologic evidence of acute HEV infection was found in 280 of 396 (71%) patients with AVH in 1987 and 12 of 99 (12%) pregnant patients with AVH in 1992. Conclusion In the absence of the availability of confirmatory testing, inferences regarding probable hepatitis epidemic etiologies can sometimes be made using surveillance data, comparing AVH incidence with AVH-associated mortality with an eye to population-based viral hepatitis control measures. Data presented here implicate HEV as the probable etiology of high mortality observed in pregnant women and in children less than 3 years of age in Uzbekistan during 1985¢1987. High mortality among pregnant women but not among children less than 3 years has been observed in previous descriptions of epidemic hepatitis E. The high mortality among younger children observed in an AVH outbreak associated with hepatitis E merits corroboration in future outbreaks.
Sporadic acute hepatitis E in the United Kingdom: an underdiagnosed phenomenon?
BACKGROUNDŚHepatitis E (HEV) is the primary cause of enterically transmitted non-A non-B hepatitis worldwide. Case reports of HEV in individuals in the United Kingdom relate to travel to endemic areas or contact with individuals who have visited these areas.?CASE REPORTSŚFour individuals presented with acute hepatitis to a hepatology clinic in a teaching hospital. Serology confirmed acute hepatitis E in all four. Investigation by the Communicable Disease Control Department established no links between the cases, no travel to an endemic area, and no contacts.?CONCLUSIONŚContrary to current belief, community acquired hepatitis E virus infection occurs sporadically in the United Kingdom and should be considered as a cause of seronegative hepatitis.???Keywords: hepatitis E; viral hepatitis; epidemiology
McCrudden, R; O'Connell, S; Farrant, T; Beaton, S; Iredale, J; Fine, D
Hepatic artery pseudoaneurysm caused by acute idiopathic pancreatitis
Hepatic artery pseudoaneurysm (HAP) is a very rare disease but in cases of complication, there is a very high mortality. The most common cause of HAP is iatrogenic trauma such as liver biopsy, transhepatic biliary drainage, cholecystectomy and hepatectomy. HAP may also occur with complications such as infections or inflammation associated with septic emboli. HAP has been reported rarely in patients with acute pancreatitis. As far as we are aware, there is no report of a case caused by acute idiopathic pancreatitis, particularly. We report a case of HAP caused by acute idiopathic pancreatitis which developed in a 61-year-old woman. The woman initially presented with acute pancreatitis due to unknown cause. After conservative management, her symptoms seemed to have improved. But eight days after admission, abdominal pain abruptly became worse again. Abdominal computed tomography (CT) was rechecked and it detected a new HAP that was not seen in a previous abdominal CT. Endoscopic retrograde cholangiopancreatography (ERCP) was performed because of a suspicion of hemobilia as a cause of aggravated abdominal pain. ERCP confirmed hemobilia by observing fresh blood clots at the opening of the ampulla and several filling defects in the distal common bile duct on cholangiogram. Without any particular treatment such as embolization or surgical ligation, HAP thrombosed spontaneously. Three months after discharge, abdominal CT demonstrated that HAP in the left lateral segment had disappeared.
Yu, Yeon Hwa; Sohn, Joo Hyun; Kim, Tae Yeob; Jeong, Jae Yoon; Han, Dong Soo; Jeon, Yong Cheol; Kim, Min Young
Clinicopathologic Features of Q Fever Patients with Acute Hepatitis
Background Q fever caused by Coxiella burnetii presents with diverse clinical and pathological features including subclinical or cholestatic hepatitis. However, the pathological features of liver biopsies from patients with Q fever have not been well described. Methods Clinical features and pathological findings of liver biopsies were reviewed in seven cases of Q fever that were confirmed by serological, microbiological, or molecular tests. Results All cases presented with fever. Liver enzymes were mildly elevated except one case with marked hyperbilirubinemia. Characteristic fibrin ring granulomas were present in three cases, epithelioid granulomas with eosinophilic infiltration in two cases, extensive extravasated fibrins without ring configuration mimicking necrotizing granuloma in one case, and acute cholangitis without granuloma in one case. All cases were treated with antibiotics for 20 days. Six cases were completely cured, but one suffered from multiorgan failure. Conclusions C. burnetii infection is uncommon, but should always be considered in patients with acute hepatitis and fever. Because variable-sized circumferential or radiating fibrin deposition was a consistent feature of the present cases, Q fever can be strongly suggested by pathological features and confirmed by serological and/or molecular tests.
Lee, Miji; Jang, Jae Jeong; Kim, Yang Soo; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Sung-Han
Risk factors for acute hepatitis B and its progression to chronic hepatitis in Shanghai, China
Background and aims: The major risk factors for acute hepatitis B (AHB) in China and the viral factors determining the progression from acute to chronic hepatitis B remain largely unknown. Methods: Epidemiological studies within a population-based surveillance for AHB in adults were performed in Shanghai, China, including 294 patients, 588 matched controls and 572 family members of the patients. Results: Invasive medical procedures, household contact with hepatitis B virus (HBV) carriers, body care and beauty treatments, and lack of HBV vaccination were independently associated with AHB. Among those risks, pedicure in bath centres emerged. Sixty-eight of 128 patients with AHB were genotyped including 33 with HBV B2 and 35 with HBV C2. Twenty-five (8.50%) of the 294 patients, including 20 with HBV C2 and 5 with HBV B2 (p?=?0.013), progressed to chronic infection. Multivariate analysis showed that HBV C2 was independently associated with chronicification of AHB. Patients with HBV B2 were younger and there was a higher proportion of women than those with HBV C2. The prevalence of HBV B2 was higher in the patients than in neighbourhood chronic carriers. The chronic carriers with HBV B2 showed higher viral loads, higher hepatitis B e antigen (HBeAg) seropositivity, and with higher proportion in men than those with HBV C2, implying that sexual contact plays a role in the transmission of HBV B2. Phylogenetic analysis showed that HBV C2 was frequently involved in transmissions within households. Conclusions: Despite lower viral load and HBeAg status in the chronic carriers, HBV C2 was more prone to causing chronic infection than was HBV B2.
Zhang, H W; Yin, J H; Li, Y T; Li, C Z; Ren, H; Gu, C Y; Wu, H Y; Liang, X S; Zhang, P; Zhao, J F; Tan, X J; Lu, W; Schaefer, S; Cao, G W
Polyphyletic Strains of Hepatitis E Virus Are Responsible for Sporadic Cases of Acute Hepatitis in Japan
Among 87 patients who were previously treated for acute hepatitis of unknown etiology between 1992 and 2001 at five hospitals in Japan, 11 (13%) patients were positive for immunoglobulin M-class antibodies to hepatitis E virus (HEV) by enzyme immunoassay and had detectable HEV RNA by reverse transcription-PCR with two independent sets of primers derived from well-conserved genomic areas in open reading frames 1 and 2. Clinical HEV infection was significantly associated with male sex (9 of 11 versus 29 of 76 patients [P < 0.01]) and older age (52 ▒ 11 [mean ▒ standard deviation] versus 41 ▒ 17 years [P < 0.05]), and its prevalence differed by geographic region (6 to 25%), with a higher rate in the northern part of Japan. At admission, the 11 patients with HEV-associated hepatitis had elevated alanine aminotransferase levels of 914 to 4,850 IU/liter, and all but 1 had elevated bilirubin levels of 1.5 to 24.0 mg/dl. The 11 HEV isolates were of genotype III or IV and were segregated into three groups with intergroup nucleotide differences of 9.5 to 22.0%. Phylogenetic analysis revealed that four isolates of genotype III were closely related to a Japanese isolate, while the other four isolates of the same genotype were nearest those from the United States. The remaining three isolates were close to known isolates of genotype IV in China and Taiwan but shared less than 88% identity with them. These results indicate that multiple genotypes of HEV cocirculate in Japan and contribute to the development of sporadic acute hepatitis, with the prevalence differing by age, sex, and geographic region.
Mizuo, Hitoshi; Suzuki, Kazuyuki; Takikawa, Yasuhiro; Sugai, Yoshiki; Tokita, Hajime; Akahane, Yoshihiro; Itoh, Keiichi; Gotanda, Yuhko; Takahashi, Masaharu; Nishizawa, Tsutomu; Okamoto, Hiroaki
The effects of acute alcohol administration on the human brain: insights from neuroimaging.
Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These inĀvivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. PMID:23978384
Bjork, James M; Gilman, Jodi M
Epstein-Barr Virus Infection with Acute Pancreatitis Associated with Cholestatic Hepatitis
Infection-induced acute hepatitis complicated with acute pancreatitis is associated with hepatitis A virus, hepatitis B virus or hepatitis E virus. Although rare, Epstein-Barr virus (EBV) infection should be considered also in the differential diagnosis if the patient has acute hepatitis combined with pancreatitis. We report a case of EBV infection with cholestatic hepatitis and pancreatitis with review of literature. An 11-year-old female was admitted due to 1-day history of abdominal pain and vomiting without any clinical symptoms of infectious mononucleosis. Diagnosis of reactivated EBV infection was made by the positive result of viral capsid antigen (VCA) IgM, VCA IgG, Epstein-Barr nuclear antigen and heterophile antibody test. We performed serologic tests and magnetic resonance cholangiopancreatography to exclude other viral or bacterial infection, autoimmune disorder, and structural problems. The patient's symptoms recovered rapidly and blood chemistry returned to normal with conservative treatment similar to previously reported cases.
Kang, Seok-Jin; Yoon, Ka-Hyun
Severe acute hepatitis E in an HIV infected patient: Successful treatment with ribavirin.
In industrialized countries, most cases of hepatitis E virus (HEV) infection in humans are autochthonous, mainly through foodborne and zoonotic transmission routes. In Europe, genotype 3 is a cause of acute self-limiting viral hepatitis, but can also be responsible for chronic hepatitis in immunocompromised patients. Ribavirin has been successfully used in the treatment of chronic hepatitis E and in a few cases of severe acute hepatitis E in immunocompetent patients. We report here the case of a 39 year-old man infected with HIV presenting with acute hepatitis E (genotype 3c). Unlike most cases, evolution was severe with a fall of prothrombin time down to 45%. Treatment with ribavirin allowed rapid viral clearance and a gradual normalization of liver function tests. PMID:24894604
Robbins, A; Lambert, D; Ehrhard, F; Brodard, V; Hentzien, M; Lebrun, D; Nguyen, Y; Tabary, T; Peron, J M; Izopet, J; Bani-Sadr, F
Involvement of autophagy in alcoholic liver injury and hepatitis C pathogenesis
This review describes the principal pathways of macroautophagy (i.e. autophagy), microautophagy and chaperone-mediated autophagy as they are currently known to occur in mammalian cells. Because of its crucial role as an accessory digestive organ, the liver has a particularly robust autophagic activity that is sensitive to changes in plasma and dietary components. Ethanol consumption causes major changes in hepatic protein and lipid metabolism and both are regulated by autophagy, which is significantly affected by hepatic ethanol metabolism. Ethanol exposure enhances autophagosome formation in liver cells, but suppresses lysosome function. Excessive ethanol consumption synergizes with hepatitis C virus (HCV) to exacerbate liver injury, as alcohol-consuming HCV patients frequently have a longer course of infection and more severe manifestations of chronic hepatitis than abstinent HCV patients. Alcohol-elicited exacerbation of HCV infection pathogenesis is related to modulation by ethanol metabolism of HCV replication. Additionally, as part of this mechanism, autophagic proteins have been shown to regulate viral (HCV) replication and their intracellular accumulation. Because ethanol induces autophagosome expression, enhanced levels of autophagic proteins may enhance HCV infectivity in liver cells of alcoholics and heavy drinkers.
Osna, Natalia A; Thomes, Paul G; Jr, Terrence M Donohue
Acute Alcohol Effects on Neuronal and Attentional Processing: Striatal Reward System and Inhibitory Sensory Interactions under Acute Ethanol Challenge
The acute influence of ethanol on cerebral activity induces complex psycho-physiological effects that are considerably more pronounced during acute ethanol influx than during maximal blood alcohol concentration (elimination phase). Despite the psychiatric and forensic relevance of these different ethanol effects, the underlying neuronal mechanisms are still unclear. In total, 20 male healthy volunteers were investigated each with three different experimental
Mathias Schreckenberger; Rainer Amberg; Armin Scheurich; Matthias Lochmann; Wolfgang Tichy; Andrķ Klega; Thomas Siessmeier; Gerhard Gr³nder; Hans-Georg Buchholz; Christian Landvogt; Jan Stauss; Klaus Mann; Peter Bartenstein; Reinhard Urban
Chronic and acute alcohol administration induced neurochemical changes in the brain: comparison of distinct zebrafish populations.
The zebrafish is increasingly utilized in the analysis of the effects of ethanol (alcohol) on brain function and behavior. We have shown significant population-dependent alcohol-induced changes in zebrafish behavior and have started to analyze alterations in dopaminergic and serotoninergic responses. Here, we analyze the effects of alcohol on levels of selected neurochemicals using a 2 ū 3 (chronic ū acute) between-subject alcohol exposure paradigm randomized for two zebrafish populations, AB and SF. Each fish first received the particular chronic treatment (0 or 0.5 vol/vol% alcohol) and subsequently the acute exposure (0, 0.5 or 1.0% alcohol). We report changes in levels of dopamine, DOPAC, serotonin, 5HIAA, glutamate, GABA, aspartate, glycine and taurine as quantified from whole brain extracts using HPLC. We also analyze monoamine oxidase and tyrosine hydroxylase enzymatic activity. The results demonstrate that compared to SF, AB is more responsive to both acute alcohol exposure and acute alcohol withdrawal at the level of neurochemistry, a finding that correlates well with prior behavioral observations and one which suggests the involvement of genes in the observed alcohol effects. We discuss correlations between the current results and prior behavioral findings, and stress the importance of characterization of zebrafish strains for future behavior genetic and psychopharmacology studies. PMID:24381007
Chatterjee, Diptendu; Shams, Soaleha; Gerlai, Robert
Predictors of Alcohol Use Among Rural Drug Users After.Disclosure of Hepatitis C Virus Status
Objective: Alcohol consumption dramatically increases the risk of liver damage among those with hepatitis C virus (HCV) infection, yet the impact of HCV status disclosure and standard informational counseling on alcohol use among rural drug users remains poorly understood. Method: In this prospective study, 503 rural Appalachian drug users were recruited using respondent-driven sampling. Participants were tested for HCV antibodies, and data on sociodemographic characteristics, lifetime and past-30-day drug and alcohol use, and psychiatric disorders were collected by interviewer-administered questionnaires. A total of 470 participants returned after 6 months for follow-up; however,4 of those had no history of alcohol use, thus leaving a final sample size of 466. Multivariate negative binomial regression was used to determine the effect of disclosure of HCV status and posttest counseling on alcohol consumption at follow-up. Results: Despite an overall decrease in drinking frequency in the cohort, those who were HCV-positive were drinking at a frequency similar to their HCV-negative counterparts at follow-up, despite posttest counseling informing them of the risks of alcohol use with an HCV diagnosis (adjusted incidence rate ratio = 1.07, 95% CI [0.72, 1.61]). Significant predictors of increased days of alcohol use after 6 months included baseline alcohol use, baseline marijuana use, and meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for antisocial personality disorder. Those using OxyContin at baseline had significantly fewer days of alcohol use at follow-up. Conclusions: HCV status disclosure and standard informational counseling alone do not curtail drinking among HCV-positive drug users in the rural setting. Targeted interventions with regard to alcohol use are warranted in order to mitigate the damage of the HCV epidemic.
Stephens, Dustin B.; Havens, Jennifer R.
Surveillance for Acute Viral Hepatitis-United States, 2007. Morbidity and Mortality Weekly Report, Vol. 58, No. SS-3, May 22, 2009.
National Technical Information Service (NTIS)
In the United States, acute viral hepatitis most frequently is caused by infection with any of three distinct viruses: hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis C virus (HCV). These unrelated viruses are transmitted through different ...
Surveillance for Acute Viral Hepatitis, United States, 2005. Morbidity and Mortality Weekly Report, Volume 56, No. SS-3, March 16, 2007.
National Technical Information Service (NTIS)
In the United States, acute viral hepatitis most frequently is caused by infection with hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis C virus (HCV). These unrelated viruses are transmitted through different routes and have different epide...
A. Wasley J. T. Miller L. Finelli
Differences in Acute Response to Alcohol between African Americans and European Americans
Background Response to alcohol is a widely studied risk factor and potential endophenotype for alcohol use disorders. Research on African American response to alcohol has been limited despite large differences in alcohol use between African Americans and European Americans. Extending our previous work on the African American portion of this sample, the current study examined differences in acute subjective response to alcohol between African Americans and European Americans. Additionally, we tested if the association between response to alcohol and past month drinking behavior and alcohol-related problems differed across race. Methods One hundred and seventy eight participants (mean age = 21.87, SD = 1.23; 57% African American) who were moderate to heavy social drinkers completed an alcohol administration study in a laboratory setting, receiving a moderate dose of alcohol (0.72g/kg alcohol for males, 0.65g/kg for females). Acute alcohol response was measured at 8 time points (i.e., baseline, 15, 30, 45, 60, 90, 120, and 150 minutes). Results Latent growth curve models showed that African Americans experienced sharper increases in stimulation on the ascending limb compared to European Americans. African American women experienced sharper increases in sedation on the ascending limb compared to European American women. Change in sedation on the ascending limb was associated with past month drinking behavior. Stimulation on the ascending limb was related to alcohol-problems for African Americans but not European Americans. Conclusions We found differences in response to alcohol across racial groups: African Americans showed a stronger response to alcohol. Future studies are needed to incorporate response to alcohol into a larger model of African American alcohol use.
Pedersen, Sarah L.; McCarthy, Denis M.
Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol.
Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH(-)) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH(-) and hepatic ADH-normal (ADH(+)) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ?1.5-fold greater in ADH(-) vs. ADH(+) deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH(-) deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis. PMID:20478324
Kaphalia, Bhupendra S; Bhopale, Kamlesh K; Kondraganti, Shakuntala; Wu, Hai; Boor, Paul J; Ansari, G A Shakeel
Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol
Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH?) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH? and hepatic ADH-normal (ADH+) deer mice fed 1, 2 or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2 months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ~1.5-fold greater in ADH? vs. ADH+ deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH? deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.
Kaphalia, Bhupendra S.; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu, Hai; Boor, Paul J.; Ansari, G.A. Shakeel
Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol Intoxication
Objective Acute alcohol intoxication increases intestinal lymph flow by unknown mechanisms, potentially impacting mucosal immunity. We tested the hypothesis that enhanced intrinsic pump function of mesenteric lymphatics contributes to increased intestinal lymph flow during alcohol intoxication. Methods Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to concious, unrestrained rats through surgically-implanted catheters. Time-matched controls received either no bolus, vehicle, or isocaloric dextrose. Thirty minutes after alcohol administration, rats were anesthetized and mesenteric collecting lymphatics were isolated and cannulated to study intrinsic pumping parameters. In separate experiments, mesenteric lymphatics were isolated to examine direct effects of alcohol on intrinsic pump activity. Results Lymphatics isolated from alcohol-intoxicated animals displayed slgnificantly decreased contraction frequency (CF) than the dextrose group, elevated stroke volume index (SVI) versus all other groups, and decreased myogenic responsiveness compared to sham. Elevating pressure from 2 to 4 cm H2O increased the volume flow index 2.4-fold in the alcohol group versus 1.4-fold for shams. Isolated lymphatics exposed to 20 mM alcohol had reduced myogenic tone, without changes in CF or SVI. Conclusions Alcohol intoxication enhances intrinsic pumping by mesenteric collecting lymphatics. Alcohol directly decreases lymphatic myogenic tone, but effects on phasic contractions occur by an unidentified mechanism.
Souza-Smith, Flavia M.; Kurtz, Kristine M.; Molina, Patricia E.; Breslin, Jerome W.
Monounsaturated fat decreases hepatic lipid content in non-alcoholic fatty liver disease in rats
Abstract AIM:T o evaluate the effects of different types of dietary fats on the ,hepatic lipid content ,and ,oxidative stress parameters,in rat liver with experimental ,non-alcoholic fatty liver disease (NAFLD). METHODS: A total,of 32 Sprague-Dawley rats were randomly,divided into fi ve groups. The rats in the control group (n = 8) were on chow diet (Group 1), rats (n =
Osamah Hussein; Masha Grosovski; Etti Lasri; Sergio Svalb; Uzi Ravid; Nimer Assy
The Effects of Disulfiram and Related Compounds on Equine Hepatic Alcohol Dehydrogenase
The reversible inhibition and the irreversible inactivation of equine hepatic alcohol dehydrogenase by disulfiram have been investigated. Disulfiram was found to be a potent competitive reversible inhibitor with KEO,I values at pH 7.0 and 10.0 of 50 ?M and 30 ?M, respectively. Reversible monodentate binding to the active site zinc is indicated by comparison with related compounds. Disulfiram was also
Bj°rn T. Langeland; John S. McKinley-McKee
Patterns of Alcohol Consumption and Acute Myocardial Infarction: A Case-Crossover Analysis
Background: Alcohol consumption has been causally related to the incidence of coronary heart disease, but the role of alcohol before the event has not been explored in depth. This study tested the hypothesis that heavy drinking (binge drinking) increases the risk of subsequent acute myocardial infarctions (AMI), whereas light to moderate drinking occasions decrease the risk. Methods: Case-crossover design of
M. G. Gerlich; A. Krõmer; G. Gmel; M. Maggiorini; T. F. L³scher; H. Rickli; G. R. Kleger; J. Rehm
Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers
The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose¢response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug¢response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies.
Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A
[Remarks on a case of acute alcoholic hallucination with delusions of jealousy].
A case of acute alcoholic hallucinosis accompanied by insane jealousy is reported, together with a discussion of various aspects of alcoholic psychosis, with consideration of the relevant literature. The most justifiable approach to the subject would appear to be one of a complex, multifactiorial ("universal genetic") nature. PMID:3283794
Postrach, F
Effects of acute alcohol intoxication on cerebral blood flow measured with PET
Regional distribution ofcerebral blood flow was assessed in a group of I3 normal social drinkers under baseline conditions and after acute alcohol intoxica- tion. Blood flow measurements were done using 150-labeled water and positron emission tomography (PET). Each subject underwent two control sessions under baseline conditions and two sessions after alcohol. Seven of the subjects were given 0.5 g\\/ kg
Nora D. Volkow; Nizar Mullani; Lance Gould; Stephen S. Adler; Robert W. Guynn; John E. Oveiall; Stephen Dewey
Effects of acute alcoholic intoxication on the progression of neuropathologic sequelae following moderate traumatic brain injury
In the United States, head injury is the number one killer of persons under the age of 44 and kills more people under the age of 34 than all other diseases combined. The prevalence of alcohol-related traumatic brain injuries (TBIs) in recent years has predominately involved young adults consuming beer while driving. Therefore, we developed a model of acute alcohol
John Matthew Sall
Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis
BACKGROUND/AIMSŚTo measure cerebral benzodiazepine receptor binding using 11C-flumazenil positron emission tomography in patients with stable chronic hepatic encephalopathy, who were also characterised by proton magnetic resonance spectroscopy.?METHODSŚSix abstinent patients of mean age 61Āyears with alcohol related cirrhosis and grade I-II hepatic encephalopathy and 11Āmatched healthy volunteers were studied. Each patient's encephalopathy was defined according to clinical, psychometric, electroencephalographic, and magnetic resonance spectroscopy criteria. Using positron emission tomography, the brain volume of distribution of 11C-flumazenil was obtained; this reflects benzodiazepine receptor availability. Proton magnetic resonance spectra were acquired at 1.5ĀT using a multivoxel technique; peak area ratios were calculated for choline, glutamine/glutamate, N-acetylaspartate, and creatine resonances.?RESULTSŚThe mean volume of distribution of 11C-flumazenil was significantly higher in the cortex, cerebellum, and the basal ganglia in the patients compared with controls (p<0.001). In the patient group, the mean glutamine/glutamate to creatine ratio was significantly increased and the mean choline to creatine ratio was significantly decreased in all brain areas, compared with healthy volunteers. However, the N-acetylaspartate to creatine ratio was unchanged compared with controls.?CONCLUSIONSŚThe spectroscopy results reflect the cerebral metabolic derangement associated with hepatic encephalopathy. Stable grade I-II chronic hepatic encephalopathy in alcohol related cirrhosis may be associated with increased cerebral benzodiazepine receptor availability. However, a direct effect of previous chronic exposure to alcohol cannot be excluded.???Keywords: benzodiazepine receptors; chronic hepatic encephalopathy; 11C-flumazenil; in vivo proton magnetic resonance spectroscopy; positron emission tomography
Jalan, R; Turjanski, N; Taylor-Robinson, S; Koepp, M; Richardson, M; Wilson, J; Bell, J; Brooks, D
Serum acid sphingomyelinase is upregulated in chronic hepatitis C infection and non alcoholic fatty liver disease.
Sphingolipids constitute bioactive molecules with functional implications in homeostasis and pathogenesis of various diseases. However, the role of sphingolipids as possible disease biomarkers in chronic liver disease remains largely unexplored. In the present study we used mass spectrometry and spectrofluorometry methods in order to quantify various sphingolipid metabolites and also assess the activity of an important corresponding regulating enzyme in the serum of 72 healthy volunteers as compared to 69 patients with non-alcoholic fatty liver disease and 69 patients with chronic hepatitis C virus infection. Our results reveal a significant upregulation of acid sphingomyelinase in the serum of patients with chronic liver disease as compared to healthy individuals (p<0.001). Especially in chronic hepatitis C infection acid sphingomyelinase activity correlated significantly with markers of hepatic injury (r=0.312, p=0.009) and showed a high discriminative power. Accumulation of various (dihydro-) ceramide species was identified in the serum of patients with non-alcoholic fatty liver disease (p<0.001) and correlated significantly to cholesterol (r=0.448, p<0.001) but showed a significant accumulation in patients with normal cholesterol values as well (p<0.001). Sphingosine, a further bioactive metabolite, was also upregulated in chronic liver disease (p<0.001). However, no significant correlation to markers of hepatic injury was identified. Conclusion: Chronic hepatitis C virus infection and non-alcoholic fatty liver disease induce a significant upregulation of serum acid sphingomyelinase which appears as a novel biomarker in chronic hepatopathies. Further studies are required to elucidate the potential of the sphingolipid signaling pathway as putative therapeutic target in chronic liver disease. PMID:24769340
Grammatikos, Georgios; M³hle, Christiane; Ferreiros, Nerea; Schroeter, Sirkka; Bogdanou, Dimitra; Schwalm, Stephanie; Hintereder, Gudrun; Kornhuber, Johannes; Zeuzem, Stefan; Sarrazin, Christoph; Pfeilschifter, Josef
Acute liver failure caused by severe acute hepatitis B: a case series from a multi-center investigation
Background Few data can be available regarding acute liver failure (ALF) caused by severe acute hepatitis B up to now. This study aims to report such cases from China. Findings We conducted a multi-center investigation on ALF from 7 tertiary hospitals in different areas of China. A total of 11 patients with ALF caused by severe acute hepatitis B were finally identified. In these patients, there were 10 male and 1 female patients. As a serious complication, apparent hemorrhage occurred in 9 patients. Eventually, in these 11 patients, 4 survived and 7 died. 4 died of heavy bleeding, 2 died of systemic inflammatory response syndrome and 1 died of irreversible coma. No patients received liver transplantation. Conclusions ALF caused by severe acute hepatitis B is worthy of formal studies based on its rarity and severity.
Psychosocial Correlates of Alcohol Use and Reduction for Individuals With Hepatitis C*
Objective: Patients with hepatitis C virus (HCV) are advised to refrain from alcohol consumption. A questionnaire was developed to measure concepts associated with alcohol use for individuals with HCV. Method: Subjects with HCV (N = 527) completed a telephone survey. Eligible respondents had screened negative for current abuse/dependence disorders (Alcohol Use Disorders Identification Test [AUDIT] ? 10). Measures of personality, self-efficacy, knowledge, readiness, coping styles, stigma, and symptoms were examined for associations with alcohol use. Results: Factor analysis supported a measurement structure of 105 items in 35 subdomains. A total of 26 subdomains had significant bivariate associations with alcohol use. Higher self-efficacy for resisting drinking in social situations was associated with lower alcohol use (r = ?.68, p < .001), as was knowledge of alcohol and HCV (r = ?.27, p < .001). Although agreeableness and marital status are typically associated with lower current drinking in samples of those with alcohol use problems, in our study agreeableness (?= .13, p < .01) and marital status (? = .08, p < .05) were modestly associated with higher current drinking. The final multivariate R2 was .55. Conclusions: The pattern of associations suggests the importance of the social aspects of drinking for drinking decisions. Existing brief interventions will need to be tailored to a contextualized psychosocial model for medical patients with HCV and AUDIT scores ? 10 to optimize effectiveness. Such future interventions should emphasize the potential medical hazards of drinking for persons with HCV, the maintenance of social relationships in the absence of alcohol use, and strategies for building confidence for resisting drinking in specific situations.
Perzynski, Adam T.; Mccormick, Richard; Webster, Noah J.; Blixen, Carol E.; Kanuch, Stephanie; Thomas, Charles L.; Mullen, Kevin D.; Dawson, Neal V.
Repeated exposure to modern volatile anaesthetics may cause chronic hepatitis as well as acute liver injury
Summary Volatile anaesthetic agents are known to cause acute hepatitis and fulminant hepatic failure in susceptible individuals. Four patients were identified with prolonged liver injury due to volatile anaesthetic-induced hepatitis. Three had liver biopsy confirmation and all gave blood for specific diagnostic tests (TFA and CYP 2E1 IgG4 antibodies). The Roussel Uclaf Causality Assessment Method (RUCAM) drug causality scale was used to determine the likelihood of volatile anaesthetics causing the chronic liver injury. We describe four cases of volatile anaesthetic hepatitis in which three evolved into chronic hepatitis. The fourth followed a more typical pattern of acute hepatitis; however, resolution took a few months. These cases all occurred with modern volatile anaesthetics, predominantly sevoflurane, and all cases were proven with specific antibody tests, liver histology and a drug causality scale. This is the first report of chronic liver injury due to volatile anaesthetic exposure.
Nicoll, Amanda; Moore, David; Njoku, Dolores; Hockey, Brad
Cardiorenal syndrome followed by acute hepatitis C in a patient with acute myeloid leukemia
Cardiorenal syndrome involves altering cardiac and renal function. These patients frequently develop resistance to diuretic therapy, so that ultrafiltration should be applied in emergency for saving them. Concomitant presence of an active hematologic malignancy represents an important complicating factor. We present the case of an elderly patient with acute myeloid leukemia, appeared on the background of myelodysplastic syndrome who, during marrow aplasia occurred after the first course of induction chemotherapy, developed a cardiorenal syndrome, which required repeated sessions of hemodialysis. Complete hematologic remission and efficiency of fluid depletion therapy allowed the second course of polychemotherapy, after which the patient developed an acute hepatitis C. After 8 months of complete hematologic remission that persists, the patient will be put on the standard antivirusologic treatment.
Mihaila, Romeo-Gabriel
Enhanced surveillance of acute hepatitis B in south-eastern Sydney
Hepatitis B is a notifi able condition in all Australian states and territories. Medical practitioners and health facilities are required to report episodes of acute disease, while laboratories must notify on posi- tive serological results. In New South Wales laboratories are required to report only the presence of hepatitis B surface antigen (HBsAg). Without clinical information, laboratory reporting of HBsAg
Roslyn G Poulos; Mark J Ferson
High-dose interferon-? 2b treatment prevents chronicity in acute hepatitis C
Acute hepatitis C takes a chronic course in 50¢80% of cases. Results with interferon treatment are conflicting. To evaluate the efficacy of high-dose interferon treatment, we initiated a pilot study in 1992 using 10 MU interferon-?2b administered subcutaneously daily until normalization of serum transaminase concentrations. Treatment was begun when a diagnosis of acute hepatitis C was established. HCV-RNA was tested
Wolfgang Vogel; Ivo Graziadei; Florian Umlauft; Christian Datz; Franz Hackl; Stefan Allinger; Kurt Gr³newald; Josef Patsch
Diet and alcohol effects on the manifestation of hepatic porphyrias.
Porphyria cutanea tarda (PCT) is the most frequently reported type of porphyria. The average patient is male more than 40 years old with a history of alcohol consumption. In women the incidence of PCT has increased with use of estrogens for birth control. The cutaneous features are those of chronic porphyrin photosensitivity on the light-exposed area of the skin: pigmentation, hirsuitism and fragility, and vesiculobullae, which has prompted the expression bullosa actinica et mechanica. One-third of the patients have glucose intolerance. PCT has been reported frequently among the Bantu people in South Africa as resulting from combinations of alcohol and cooking in ironware. The average patient has a higher than normal hematocrit, which is used as a guide to treatment by phlebotomy ranging from 8 to 14 units removed every 2-4 wk. Chemically induced PCT has been reported with chlorinated hydrocarbons, the best-known of which is hexachlorobenzene (HCB). Porphyria was noted in more than 3,000 patients in southeast Turkey between 1955 and 1961, because of consumption of seed wheat treated with HCB. In addition, more than 1,000 children under the age of 1 year died because HCB was transferred from the mother, either via the placenta or through breast milk. PMID:3556614
Cripps, D J
Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women.
The authors investigated the dose-effect relation between alcohol drinking and hepatocellular carcinoma (HCC) in men and women separately, also considering hepatitis B and hepatitis C virus infections. They enrolled 464 subjects (380 men) with a first diagnosis of HCC as cases and 824 subjects (686 men) unaffected by hepatic diseases as controls; all were hospitalized in Brescia, northern Italy, in 1995-2000. Spline regression models showed a steady linear increase in the odds ratio of HCC for increasing alcohol intake, for values of >60 g of ethanol per day, with no substantial differences between men and women. Duration of drinking and age at start had no effect on the odds ratio when alcohol intake was considered. Former drinkers who had stopped 1-10 years previously had a higher risk of HCC than current drinkers did. The effect of alcohol drinking was evident even in the absence of hepatitis B or hepatitis C virus infection. In addition, a synergism between alcohol drinking and either infection was found, with approximately a twofold increase in the odds ratio for each hepatitis virus infection for drinkers of >60 g per day. PMID:11836196
Donato, F; Tagger, A; Gelatti, U; Parrinello, G; Boffetta, P; Albertini, A; Decarli, A; Trevisi, P; Ribero, M L; Martelli, C; Porru, S; Nardi, G
Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor
Objective Alcohol intake increases the risk of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) and is associated with poor outcomes in patients who develop these syndromes. No specific therapies are currently available to treat or decrease the risk of ARDS in patients with alcoholism. We have recently shown increased levels of lung adenosine inhibit alveolar fluid clearance, an important predictor of outcome in patients with ARDS. We hypothesized that alcohol might worsen lung injury by increasing lung adenosine levels, resulting in impaired active Na+ transport in the lung. Methods We treated wild-type mice with alcohol administered i.p. to achieve blood alcohol levels associated with moderate to severe intoxication and measured the rate of alveolar fluid clearance and Na,K-ATPase expression in peripheral lung tissue and assessed the effect of alcohol on survival during exposure to hyperoxia. We used primary rat alveolar type II cells to investigate the mechanisms by which alcohol regulates alveolar Na+ transport. Results Exposure to alcohol reduced alveolar fluid clearance, downregulated Na,K-ATPase in the lung tissue and worsened hyperoxia-induced lung injury. Alcohol caused an increase in BAL fluid adenosine levels. A similar increase in lung adenosine levels was observed after exposure to hyperoxia. In primary rat alveolar type II cells alcohol and adenosine decreased the abundance of the Na,K-ATPase at the basolateral membrane via a mechanism that required activation of the AMPK. Conclusions Alcohol decreases alveolar fluid clearance and impairs survival from acute lung injury. Alcohol induced increases in lung adenosine levels may be responsible for reduction in alveolar fluid clearance and associated worsening of lung injury.
Urich, Daniela; Soberanes, Saul; Manghi, Tomas S.; Chiarella, Sergio E.; Chandel, Navdeep S.; Budinger, G. R. Scott; Mutlu, Gokhan M.
Duration of viraemia in Chinese acute sporadic hepatitis E.
Acute sporadic hepatitis E (ASHE) cases induced by hepatitis E virus genotype 4 (HEV-4) are increasing in China. Our study aimed to estimate the duration of HEV-4 viraemia in Chinese ASHE. A total of 619 serum specimens from 499 ASHE patients were examined for the presence of HEV RNA. The association between viraemia detection and serum sampling time was compared between subtypes. The cumulative probability of HEV viraemia detection was determined using Kaplan-Meier survival analysis, and the viraemia duration was estimated. A total of 42.7 % of serum specimens were positive for HEV RNA and all the isolated strains were identified as genotype 4 and subsequently assigned to five subtypes. Among the patients infected with subtypes 4d and 4i, the time interval from the initiation of clinical symptoms to serum specimen sampling was shorter than that among the patients with subtypes 4a, 4b and 4h. Kaplan-Meier analysis was conducted with 101 sequential specimens as well as with both 101 sequential specimens and 236 single negative specimens. The cumulative probability of HEV-4 viraemia detection was estimated to decline quickly to approximately 10 % within 32 days after the initiation of clinical symptoms and then to decline very slowly to 5 % by the 41st day and to zero by the 131st day. The majority of ASHE cases maintain detectable HEV-4 viraemia within one month after onset, whereas a small portion of cases maintain long-term viraemia and may act as a reservoir for further transmission. PMID:24241947
Lu, Y-H; Qian, H-Z; Hu, A-Q; Ren, H; Qin, X; Jiang, Q-W; Zheng, Y-J
Contrasting behavioral effects of acute nicotine and chronic smoking in detoxified alcoholics
BackgroundCurrent literature suggests that acute nicotine administration provides a compensatory mechanism by which alcoholics might alleviate attentional deficits. In contrast, chronic smoking is increasingly recognized as negatively affecting neurobehavioral integrity. These opposing effects have not been simultaneously examined. Thus, we sought to a) extend previous work by exploring the effects of acute nicotine effects on vigilance components of attention and
Jeff Boissoneault; Rebecca Gilbertson; Robert Prather; Sara Jo Nixon
[Acute pancreatitis and acalculous cholecystitis associated with viral hepatitis A].
We report the case of a 14 year-old male from Lima. He is a student with a history of bronchial asthma since age 4 receives conditional salbutamol, corticosteroids used for asthma attacks (a crisis in 2010, 1 month ago) Refuses surgery or transfusions. He presented with a two weeks for abdominal pain, nausea, fever, and jaundice. Epigastric pain is colicky and radiated back to righ upper quadrant, refers in addition to nausea and fever, for ten days notice jaundice of skin and sclera. On examen he was lucid, with jaundice of skin and mucous membranes. There was no palpable lymph nodes, abdomen with bowel sounds, soft, depressible, liver span of 15cm, positive Murphy, no peritonitis. The laboratory findings showed hemoglobin 13gr, MCV 90, platelets 461.000/mm3, WBC 4320/mm, lymphocytes 1700 (39%). total bilirubin: 8.8, B Direct: 7.6, ALT (alanine aminotransferase): 3016, AST (aspartate aminotransferase): 984, alkaline phosphatase: 250, albumin: 3.34gr%, globulin: 2.8, amylase: 589 (high serum amylase), TP: 17, INR: 1.6, VHA IgM positive. 89 mg glucose, urea 19 mg%, creatinine 0.5 mg Hemoglobin 13gr, MCV 90 Platelet 461000/mm3, WBC 4320/mm, Lymphocytes 1700 (39%). The nuclear magnetic resonance showed hepatomegaly associated with thickening of gallbladder wall without stones up to 11mm inside. No bile duct dilatation, bile duct 4mm, pancreas increased prevalence of body size. Mild splenomegaly and free fluid in the space of Morrison and right flank. Abdominal ultrasound revealed a gallbladder wall thickness (11mm), without stones in his light. Pancreas to increase volume with peripancreatic fluid free perivesicular with a volume of 430 cc. Findings consistent with acute acalculous cholecystitis and acute pancreatitis. CT-scan showed enlarged pancreas with predominance of body and tail with peripancreatic edema; the gallbladder was thickening. We report this case because the extrahepatic manifestations of viral hepatitis A infection are uncommon, specially the associated with acute acalculous cholecystitis and acute pancreatitis simultaneous. PMID:21836659
Arcana, Ronald; Frisancho, Oscar
Risk Factors and Immune Response to Hepatitis E viral Infection among Acute Hepatitis Patients in Assiut, Egypt
Hepatitis E virus (HEV) infection is a common cause of acute viral hepatitis (AVH) in Egypt. We aimed to identify risk factors of HEV among acute hepatitis cases, measure HEV specific immune response to differentiate between symptomatic and asymptomatic infections. The study included symptomatic acute hepatitis (AH) patients (n=235) and asymptomatic contacts (n=200) to HEV cases. They completed a lifestyle questionnaire, screened for common hepatotropic viruses. Blood and serum samples were collected from patients and contacts after onset of disease and follow-up samples collected until convalescence. PBMC were separated and tested for specific HEV T-cell response by INF-ELISPOT assay. Serum samples were tested for IgM and IgG anti-hepatitis E virus by ELISA. IgM antibodies to HAV were detected in 19 patients (8.1%), 37 (15.7%) with HBV, 10 (4.3%) with HCV. HEV infection was identified in 42 (16%) patients with AVH. Of the 200 contacts, 14 (7%) had serological evidence of recent HEV asymptomatic infection, showed stronger CMI responses than HEV infected subjects (2540 ▒ 28 and 182 ▒ 389 ISCs/106 cells, respectively; P <0.05). In conclusion, HEV is a major cause of AVH in Egypt. Asymptomatic HEV patients are likely to have stronger immune responses including CMI responses, than symptomatic cases.
Seif Eldin, Salwa S.; Seddik, Ismail; Daef, Enas A.; Shata, M.T.; Raafat, Marwa; Baky, Laila Abdel; Nafeh, MA
Clinical features and outcome of acute hepatitis B in pregnancy
Background The impact of pregnancy on the clinical course of acute hepatitis B (AHB) is still largely unclear, mainly because most studies have not included matched controls. This study was conducted to investigate the clinical features and outcome of AHB in pregnancy using matched controls. Methods Consecutive AHB inpatients who were admitted to Jinan Infectious Disease Hospital, Jinan, between January 2006 and December 2010 were evaluated and followed. Demographic data, clinical manifestations, and results of laboratory tests were compared between pregnant patients and age and sex matched non-pregnant patients at admission, discharge, and final follow-up. Results A total of 618 AHB inpatients were identified during the study period. 22 pregnant patients and 87 age and sex matched non-pregnant patients were enrolled in this study. Prodromal fever was less common (0% vs. 20.7%, P?=?0.02), serum alanine aminotransferase levels were significantly lower, and HBsAg?>?250ĀIU/mL rate and serum bilirubin levels were significantly higher in pregnant patients than in non-pregnant patients. After a mean (range) of 7(5.2-8.3) months follow-up, 18.2% pregnant patients and 4.6% non-pregnant patients were still HBsAg positive (P?=?0.03). For pregnant patients, the relative risk (95% confidence interval) of HBsAg positive at the end of follow-up was 4.6 (1.1-20.2). The median (95% confidence interval) days of HBsAg seroclearance form disease onset in pregnant and non-pregnant patients were 145.0 (110.5-179.5) and 80.0 (62.6-97.4), respectively. Conclusions The HBsAg loss and seroconversion were delayed and lower in pregnant patients. Pregnancy might be a possible risk of chronicity following acute HBV infection.
Acute Alcohol Consumption Disrupts the Hormonal Milieu of Lactating Women
Despite the lack of scientific evidence to support the claim that alcohol is a galactagogue, lactating women have been advisedtodrinkalcoholasanaidtolactationforcenturies.To test the hypothesis that alcohol consumption affects the hor- monal response in lactating women, we conducted a within- subjects design study in which 17 women consumed a 0.4 g\\/kg dose of alcohol in orange juice during one test session and
Julie A. Mennella; M. Yanina Pepino; Karen L. Teff
Regulation of FOXO3 by phosphorylation and methylation in hepatitis C virus infection and alcohol exposure.
Hepatitis C virus (HCV) infection produces chronic liver injury that is significantly exacerbated by alcohol consumption. While multiple mechanisms contribute to this synergy, a viral-induced loss of antioxidant responses has been shown to play an important role. This study examined the effects of HCV infection and alcohol on the regulation of the transcription factor FOXO3, an important regulator of Mn-superoxide dismutase (SOD2) expression, a tumor suppressor, and a component of the hepatic antioxidant response system. FOXO3 was activated by either HCV or alcohol alone but suppressed by the combination. To understand this paradoxical result, we applied a capillary isoelectric focusing (IEF) method to determine the pattern of FOXO3 posttranslational modifications (PTMs) induced by HCV and alcohol. We observed the presence of multiple different nuclear and cytosolic species of FOXO3 and used antiphosphoserine, acetyl-lysine, methylarginine, and ubiquitin antibodies to identify the PTM patterns present in each species. HCV caused multiple changes including phosphorylation of FOXO3 at S-574, a novel c-Jun N-terminal kinase (JNK) site, which promoted nuclear translocation and transcription. Ethanol suppressed arginine-methylation of FOXO3 promoting nuclear export and degradation of the JNK phosphorylated form. Human liver biopsy samples showed the presence of the HCV-specific form of FOXO3 in HCV-infected livers but not in normal liver or nonalcoholic steatohepatitis. Conclusion: The development of this novel IEF method for the simultaneous quantification of differently modified FOXO3 species allowed us to demonstrate how HCV and alcohol combine to modify a complex pattern of FOXO3 PTMs that contribute to pathogenesis. This approach will allow further dissection of the role of protein PTMs in viral liver disease. PMID:23857333
Tikhanovich, Irina; Kuravi, Sudhakiranmayi; Campbell, Roosevelt V; Kharbanda, Kusum K; Artigues, Antonio; Villar, Maria T; Weinman, Steven A
Chronic ecstasy (3,4-methylenedioxymetamphetamine) abuse: a recurrent and unpredictable cause of severe acute hepatitis.
Fifteen reports of hepatitis induced by ecstasy (MDMA, 3,4-methylenedioxymetamphetamine) have been published over the last 3 years. With the increasing enthusiasm for "Rave" parties, the incidence appears to be increasing, and is an important and often concealed cause of acute hepatitis in young people. We report two cases of recurrent ecstasy-associated hepatitis where the interval between drug consumption and jaundice was variable and the link therefore initially obscured. Liver biopsies of both patients showed acute hepatitis. One was of relatively mild degree, and the other was severe, with features suggesting auto-immune hepatitis. Both cases resolved spontaneously. A high index of suspicion and careful specific enquiry are necessary to make the diagnosis and warn the patient to abstain in future, since subsequent attacks may be fatal and insidious chronic damage may occur. PMID:8912157
Fidler, H; Dhillon, A; Gertner, D; Burroughs, A
Seroconversion of acute hepatitis B by antiretroviral therapy in an HIV-1 infected patient.
A 33-year-old man with human immunodeficiency virus type1 (HIV-1) infection was admitted because of acute hepatitis B. His serum alanine aminotransferase level was 1200 IU/mL and CD4 cells count was 268/mm3. Antiretroviral therapy including tenofovir and emtricitabine, which suppresses both HIV and hepatitis B virus (HBV) replication, was initiated. The liver enzymes decreased dramatically. The viral loads of both HIV-1 and HBV were suppressed below detectable limits. Seroconversion from hepatitis B surface antigen to hepatitis B surface antibody was acquired 19 weeks later. In this case, the initiation of antiretroviral therapy with anti-HBV activity during the acute phase of hepatitis B had a favourable effect on HBV serostatus. PMID:21086945
Ikeda-Kamimura, Mahoko; Horiba, Masahide
Combined effects of alcohol and hepatitis C: a secondary analysis of alcohol use biomarkers and high-risk behaviors from two medication trials for alcohol dependence
Objectives This goal of this secondary analysis was to examine the combined effect of HCV infection and recent alcohol use on baseline biologic markers of alcohol consumption in two outpatient medication trials for alcohol dependence. In addition, the relationship between Hepatitis C virus (HCV) infection and behavioral risk factors for HCV infection in these clinical populations were examined. Methods Data (n = 345) from two randomized, placebo-controlled trials of naltrexone and psychosocial treatment for alcohol dependence (Study I, n = 212) and comorbid alcohol and cocaine dependence (Study II, n = 133) were used to examine baseline measures of HCV risk behaviors (injection drug use, needle sharing), and biomarkers of alcohol use (AST, ALT, GGT and CDT) were compared by HCV serostatus first within each study and then across studies. Results Although groups had differing sociodemographic profiles (as indicated by race, marital status, level of education) subjects in Study I exhibited no statistically significant differences from the Study II cohort in HCV prevalence (12.7 vs. 20.0 percent, p = 0.07), lifetime history of injection drug use (13.8 vs. 22.0%, p = 0.74), lifetime history of needle sharing (9.1 vs. 18.0 percent, p = 0.62). As such, the data from both studies were analyzed together. Regardless of drinking status, HCV infection was significantly associated with an upward shift in the baseline level of ALT, AST, and GGT (p<0.006 for all measures) and a downward shift in baseline CDT (p = 0.002). When using standard laboratory cutoff values to determine clinically significant elevations, HCV seropositivity was significantly associated with elevations in ALT, AST, GGT (p<0.001), and with decreases in CDT (p = .002). Conclusions These data emphasize the importance of evaluating HCV infection and HCV risk behaviors at intake in medication trials for alcohol dependence and also raise questions regarding the use of cut off scores for ALT, AST, GGT and CDT levels as biologic markers of alcohol use in subjects when HCV status is unknown.
Plebani, Jennifer G.; Tirado, Carlos F.; Pettinati, Helen M.; Kampman, Kyle M.; Volpicelli, Joseph R.; Oslin, David W.
Kinetics of Acute Hepatitis B Virus Infection in Humans
Using patient data from a unique single source outbreak of hepatitis B virus (HBV) infection, we have characterized the kinetics of acute HBV infection by monitoring viral turnover in the serum during the late incubation and clinical phases of the disease in humans. HBV replicates rapidly with minimally estimated doubling times ranging between 2.2 and 5.8 d (mean 3.7 ▒ 1.5 d). After a peak viral load in serum of nearly 1010 HBV DNA copies/ml is attained, clearance of HBV DNA follows a two or three phase decay pattern with an initial rapid decline characterized by mean half-life (t1/2) of 3.7 ▒ 1.2 d, similar to the t1/2 observed in the noncytolytic clearance of covalently closed circular DNA for other hepadnaviruses. The final phase of virion clearance occurs at a variable rate (t1/2 of 4.8 to 284 d) and may relate to the rate of loss of infected hepatocytes. Free virus has a mean t1/2 of at most 1.2 ▒ 0.6 d. We estimate a peak HBV production rate of at least 1013 virions/day and a maximum production rate of an infected hepatocyte of 200¢1,000 virions/day, on average. At this peak rate of virion production we estimate that every possible single and most double mutations would be created each day.
Whalley, Simon A.; Murray, John M.; Brown, Dave; Webster, George J.M.; Emery, Vincent C.; Dusheiko, Geoffrey M.; Perelson, Alan S.
Acute Pancreatitis Associated with Interferon and Ribavirin Therapy in Patients with Chronic Hepatitis C
Acute pancreatitis is a rare complication of interferon (IFN) and ribavirin (RBV) therapy. The aimof this study was to determine the incidence, clinical presentation, and outcome of acute pancreatitisin patients with chronic hepatitis C virus (HCV) infection treated with IFN and RBV combinationtherapy. We conducted a retrospective review of 1706 HCV-infected patients treated with IFN a-2band RBV. The diagnosis of
Swati Chaudhari; James Park; Bhupinderjit S. Anand; Neville R. Pimstone; Douglas T. Dieterich; Steven Batash; Edmund J. Bini
Metadoxine in the treatment of acute and chronic alcoholism: a review.
Alcohol abuse and alcoholism are responsible for a wide variety of medical problems. The pharmaco-therapeutic aspect of alcoholism includes the use of drugs, with different actions and objectives. Among them, metadoxine seems to be of interest. Metadoxine is able to accelerate the elimination of alcohol from the blood and tissues, to help restore the functional structure of the liver and to relieve neuro-psychological disorders associated with alcohol intoxication. Metadoxine also seems to be safe; in more than 15 years of post-marketing surveillance only minor aspecific and reversible events were monitored in patients exposed to the treatment. In this review the preclinical and clinical results obtained using metadoxine in acute and chronic alcohol intoxication are reported. PMID:14611722
Addolorato, G; Ancona, C; Capristo, E; Gasbarrini, G
Alcohol Consumption and Development of Acute Respiratory Distress Syndrome: A Population-Based Study
This retrospective population-based study evaluated the effects of alcohol consumption on the development of acute respiratory distress syndrome (ARDS). Alcohol consumption was quantified based on patient and/or family provided information at the time of hospital admission. ARDS was defined according to American-European consensus conference (AECC). From 1,422 critically ill Olmsted county residents, 1,357 had information about alcohol use in their medical records, 77 (6%) of whom developed ARDS. A history of significant alcohol consumption (more than two drinks per day) was reported in 97 (7%) of patients. When adjusted for underlying ARDS risk factors (aspiration, chemotherapy, high-risk surgery, pancreatitis, sepsis, shock), smoking, cirrhosis and gender, history of significant alcohol consumption was associated with increased risk of ARDS development (odds ratio 2.9, 95% CI 1.3¢6.2). This population-based study confirmed that excessive alcohol consumption is associated with higher risk of ARDS.
Thakur, Lokendra; Kojicic, Marija; Thakur, Sweta J.; Pieper, Matthew S.; Kashyap, Rahul; Trillo-Alvarez, Cesar A.; Javier, Fernandez; Cartin-Ceba, Rodrigo; Gajic, Ognjen
Alcohol consumption and development of acute respiratory distress syndrome: a population-based study.
This retrospective population-based study evaluated the effects of alcohol consumption on the development of acute respiratory distress syndrome (ARDS). Alcohol consumption was quantified based on patient and/or family provided information at the time of hospital admission. ARDS was defined according to American-European consensus conference (AECC). From 1,422 critically ill Olmsted county residents, 1,357 had information about alcohol use in their medical records, 77 (6%) of whom developed ARDS. A history of significant alcohol consumption (more than two drinks per day) was reported in 97 (7%) of patients. When adjusted for underlying ARDS risk factors (aspiration, chemotherapy, high-risk surgery, pancreatitis, sepsis, shock), smoking, cirrhosis and gender, history of significant alcohol consumption was associated with increased risk of ARDS development (odds ratio 2.9, 95% CI 1.3-6.2). This population-based study confirmed that excessive alcohol consumption is associated with higher risk of ARDS. PMID:19826554
Thakur, Lokendra; Kojicic, Marija; Thakur, Sweta J; Pieper, Matthew S; Kashyap, Rahul; Trillo-Alvarez, Cesar A; Javier, Fernandez; Cartin-Ceba, Rodrigo; Gajic, Ognjen
Hepatic encephalopathy is a serious and potentially fatal complication of both acute and chronic liver disease, arising as a result of hepatocellular failure, cirrhosis and/or portal-systemic shunting (Ferenci et al, 2002). It reflects a broad spectrum of neuropsychiatric abnormalities, encompassing a range of defects in psychomotor, locomotive, cognitive, emotional and behavioural functions (Prakash and Mullen, 2010). Hepatic encephalopathy is either overt or minimal. While overt hepatic encephalopathy can be diagnosed using bedside clinical tests, minimal hepatic encephalopathy is clinically invisible and requires psychometric testing to diagnose. The rising prevalence of end-stage viral hepatitis-related liver disease, coupled with the growing problem of alcoholic and non-alcoholic fatty liver disease, has significantly increased the burden of disease from cirrhosis (Mooney et al, 2007; Fleming et al, 2008), so recognition and appropriate management of the manifestations of decompensating cirrhosis (including hepatic encephalopathy) is essential. Hepatic encephalopathy has a substantial societal burden because of its impact on survival, quality of life and daily functioning, including an impaired ability to drive, leaving patients especially vulnerable to road traffic accidents (Ferenci et al, 2002; Prakash and Mullen, 2010). PMID:22504749
Patel, D; McPhail, M J W; Cobbold, J F L; Taylor-Robinson, S D
Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity
The aim of this study was to determine by multivariate analysis how alcohol and other factors affect the clinical course and outcome in patients with acetaminophen (paracetamol) poisoning. A total of 645 consecutive patients admitted from 1994 to 2000 with single-dose acetaminophen poisoning were studied, giving special attention to alcohol history, time between overdose and intravenous N-acetylcysteine (NAC) treatment (ōtime
Lars E. Schmidt; Kim Dalhoff; Henrik Enghusen Poulsen
Disulfiram--alcohol reaction mimicking an acute coronary syndrome.
Disulfiram treatment for alcohol dependence is used with acceptable outcomes. By inhibiting the aldehyde dehydrogenase enzyme, this treatment increases acetaldehyde concentration after the ingestion of alcohol causing an unpleasant disulfiram-alcohol reaction. Typical symptoms include flushing, headache, nausea, vomiting, sweating, vertigo, and lightheadedness. However, there have also been descriptions of more serious reactions including severe hypotension, arrhythmias, myocardial infarction, and cardiovascular collapse. We report a patient with a severe disulfiram-alcohol reaction marked by flushing, confusion, generalized malaise, epigastric pain, and hypotension. Cardiac biomarker and electrocardiographic changes were suggestive of non-ST-elevation myocardial infarction (NSTEMI). Left heart catheterization showed no angiographic evidence of coronary artery disease. Because of the frequency of alcohol dependence and its treatment with disulfiram, it is critical for physicians to be aware of these types of life-threatening complications. PMID:24741856
Amuchastegui, Tomas; Amuchastegui, Marcos; Donohue, Thomas
Kudzu Extract Treatment Does Not Increase the Intoxicating Effects of Acute Alcohol in Human Volunteers
Background Isoflavone administration in the form of a purified extract from the herbal medication kudzu root has been shown to reduce, but not eliminate, alcohol consumption in alcohol-abusing and alcohol-dependent men. The precise mechanism of this action is unknown, but one possible explanation for these results is that the isoflavones in kudzu might actually increase the intensity or duration of alcoholÆs effects and thus delay the desire for subsequent drinks. The present study was designed to test this hypothesis. Methods Twelve (12) healthy adult men and women (27.5▒1.89 yrs old) who consumed moderate amounts of alcohol (7.8▒0.63 drinks/week) participated in a double-blind, placebo-controlled crossover study in which they were treated with either kudzu extract (total isoflavone dose of 750 mg/day) or matched placebo for nine days. On days 8 and 9, participants received an acute challenge of ethyl alcohol (either 0.35 or 0.7 g/kg alcohol). During the challenges the following measures were collected: subjective effects, psychomotor (body sway), cognitive performance (vigilance/reaction time), physiological measures (heart rate and skin temperature), and plasma ethanol concentration. Results Alcohol resulted in a dose-related alteration in subjective measures of intoxication, impairment of stance stability, and vigilance/reaction time. Kudzu extract did not alter participantsÆ subjective responses to the alcohol challenge or to alcoholÆs effects on stance stability or vigilance/reaction time. However, individuals treated with kudzu extract experienced a slightly more rapid rise in plasma ethanol levels, but only after the 0.7 g/kg dose. This transient effect during the first 30 minutes of the ascending plasma alcohol curve lasted only 10-15 minutes; there were no differences in peak plasma alcohol levels or alcohol elimination kinetics. Additionally, kudzu pretreatment enhanced the effects of the 0.7 g/kg dose of alcohol on heart rate and skin temperature. Conclusions These data suggest that individuals who drink alcohol while being treated with kudzu extract experience no adverse consequences and further, the reported reductions in alcohol intake after kudzu extract treatment are not related to an alteration in alcoholÆs subjective or psychomotor effects.
Penetar, David M.; MacLean, Robert R.; McNeil, Jane F.; Lukas, Scott E.
Absence of Perilipin 2 Prevents Hepatic Steatosis, Glucose Intolerance and Ceramide Accumulation in Alcohol-Fed Mice
Background Perilipin 2 (Plin2) is a lipid droplet protein that has roles in both lipid and glucose homeostasis. An increase in Plin2 in liver is associated with the development of steatosis, glucose intolerance, and ceramide accumulation in alcoholic liver disease. We investigated the role of Plin2 on energy balance and glucose and lipid homeostasis in wildtype and Plin2 knockout (Plin2KO) mice chronically fed a Lieber-DeCarli liquid ethanol or control diet for six weeks. Methods We performed in vivo measurements of energy intake and expenditure; body composition; and glucose tolerance. After sacrifice, liver was dissected for histology and lipid analysis. Results We found that neither genotype nor diet had a significant effect on final weight, body composition, or energy intake between WT and Plin2KO mice fed alcohol or control diets. Additionally, alcohol feeding did not affect oxygen consumption or carbon dioxide production in Plin2KO mice. We performed glucose tolerance testing and observed that alcohol feeding failed to impair glucose tolerance in Plin2KO mice. Most notably, absence of Plin2 prevented hepatic steatosis and ceramide accumulation in alcohol-fed mice. These changes were related to downregulation of genes involved in lipogenesis and triglyceride synthesis. Conclusions Plin2KO mice chronically fed alcohol are protected from hepatic steatosis, glucose intolerance, and hepatic ceramide accumulation, suggesting a critical pathogenic role of Plin2 in experimental alcoholic liver disease.
Carr, Rotonya M.; Peralta, Giselle; Yin, Xiaoyan; Ahima, Rexford S.
Alcohol Consumption Decisions among Nonabusing Drinkers Diagnosed with Hepatitis C: An Exploratory Sequential Mixed Methods Study.
Most studies of decisions to curtail alcohol consumption reflect experiences of abusing drinkers. We employ an exploratory sequential research design to explore the applicability of this research to the experience of nonabusing drinkers advised to curtail alcohol consumption after a Hepatitis C diagnosis. A qualitative component identified 17 new decision factors not reflected in an inventory of factors based on synthesis of existing scales. We triangulated qualitative data by supplementing semi-structured interviews with Internet postings. A quantitative component estimated prevalence and association with current drinking of these new decision factors. Patients who quit drinking tended to attribute post-diagnosis drinking to occasional triggers, whereas patients who were still drinking were more likely to endorse rationales not tied to specific triggers. PMID:20046861
Stoller, Eleanor Palo; Webster, Noah J; Blixen, Carol E; McCormick, Richard A; Hund, Andrew J; Perzynski, Adam T; Kanuch, Stephanie W; Thomas, Charles L; Kercher, Kyle; Dawson, Neal V
Alcohol Consumption Decisions among Nonabusing Drinkers Diagnosed with Hepatitis C: An Exploratory Sequential Mixed Methods Study
Most studies of decisions to curtail alcohol consumption reflect experiences of abusing drinkers. We employ an exploratory sequential research design to explore the applicability of this research to the experience of nonabusing drinkers advised to curtail alcohol consumption after a Hepatitis C diagnosis. A qualitative component identified 17 new decision factors not reflected in an inventory of factors based on synthesis of existing scales. We triangulated qualitative data by supplementing semi-structured interviews with Internet postings. A quantitative component estimated prevalence and association with current drinking of these new decision factors. Patients who quit drinking tended to attribute post-diagnosis drinking to occasional triggers, whereas patients who were still drinking were more likely to endorse rationales not tied to specific triggers.
Stoller, Eleanor Palo; Webster, Noah J.; Blixen, Carol E.; McCormick, Richard A.; Hund, Andrew J.; Perzynski, Adam T.; Kanuch, Stephanie W.; Thomas, Charles L.; Kercher, Kyle; Dawson, Neal V.
Diagnosis of acute hepatitis C virus infection and estimated incidence in low- and high-risk English populations.
The diagnosis of acute hepatitis C virus (HCV) infection is not straightforward; few people exhibit clinical symptoms and genome/antigen detection techniques do not indicate when infection had occurred. Here, a strategy to detect HCV RNA in the absence of antibody ('window-period') for diagnosis of acute infection is assessed. The sentinel surveillance of hepatitis testing study was used to retrospectively identify anti-HCV negative samples from high-risk individuals (2002-2003), for testing singly for HCV RNA. Additional samples were identified prospectively (2005) and tested in pools for HCV RNA. Positive samples were genotyped. Incidence and costs of adopting the pooling strategy were estimated. In the retrospective study, 8/390 (2.1%) samples were confirmed HCV RNA positive, anti-HCV negative. Prospectively, 3237 samples were tested in 325 pools. Five positive pools identified four confirmed HCV RNA positive patients (one false positive). Estimated incidence was 12.9 per 100 person-years in injecting drug users (IDUs) (retrospective study) and 3.7 per 100 person-years among drug/alcohol services and prison attendees (prospective study). Estimated costs were pound 850 per positive sample, in areas of higher risk. The yield from a window-period strategy depends upon the population tested. Pooled HCV RNA testing of anti-HCV negative samples from the current IDUs is realistic and relatively inexpensive to identify recently infected individuals. PMID:18637073
Brant, L J; Ramsay, M E; Balogun, M A; Boxall, E; Hale, A; Hurrelle, M; Kaluba, L; Klapper, P; Lewis, D; Patel, B C; Parry, J; Irving, W L
Investigating an outbreak of acute viral hepatitis caused by hepatitis E virus variants in Karachi, South Pakistan.
Hepatitis E is a classic water-borne disease in developing countries. Detection of anti-HEV IgM and IgG antibodies, in addition to HEV RNA are useful epidemiological markers in diagnosis of hepatitis E. This study was conducted to investigate an outbreak of acute viral hepatitis in South-Pakistan. Anti-HEV IgM and IgG were assessed comparatively with serological kits manufactured by Abbott, Cosmic, TGH, and Wantai, selecting HEV RNA as reference assay. Molecular evolutionary analysis was performed by phylogeny and HEV spread time analysis by Bayesian Coalescent Theory approach. Of the 89 patients, 24 (26.9%) did not have acute hepatitis viral marker. Of the remaining 65 cases, 4 (6.1%) were positive for anti-HAV IgM, one (1.5%) for anti-HBc IgM, 2 (3%) for HCV, 53 (81.5%) for anti-HEV IgM, and 5 (7.7%) were hepatitis-negative. The Wantai test was 100% sensitive and specific followed by Cosmic (98.1% and 100%), TGH (98.1% and 97.2%) and Abbott (79.2% and 83.3%). Two HEV variant strains were detected by phylogeny responsible for this acute hepatitis outbreak. Estimates on demographic history of HEV showed that HEV in Pakistan has remained at a steady nonexpanding phase from around 1970 to the year 2005, in which it expanded explosively with the emergence of new HEV variants. In conclusion, the limited sensitivity of available assay (Abbott anti-HEV EIA) may be a concern in HEV diagnosis in Pakistan. This study cautions that the dissemination of the variant strains to other areas of Pakistan may lead to explosive HEV outbreaks. PMID:21328376
Khan, Anis; Tanaka, Yasuhito; Kurbanov, Fuat; Elkady, Abeer; Abbas, Zaigham; Azam, Zahid; Subhan, Amna; Raza, Sajjad; Razza, Sajjad; Hamid, Saeed; Jafri, Wasim; Shih, James; Xia, Ningshao; Takahashi, Kazuaki; Mishiro, Shunji; Mizokami, Masashi
Acute and chronic alcohol dose: population differences in behavior and neurochemistry of zebrafish
The zebrafish has been in the forefront of developmental genetics for decades and has also been gaining attention in neurobehavioral genetics. It has been proposed to model alcohol-induced changes in human brain function and behavior. Here, adult zebrafish populations, AB and SF (short-fin wild type), were exposed to chronic treatment (several days in 0.00% or 0.50% alcohol v/v) and a subsequent acute treatment (1 h in 0.00%, 0.25%, 0.50% or 1.00% alcohol). Behavioral responses of zebrafish to computer-animated images, including a zebrafish shoal and a predator, were quantified using videotracking. Neurochemical changes in the dopaminergic and serotoninergic systems in the brain of the fish were measured using high-precision liquid chromatography with electrochemical detection. The results showed genetic differences in numerous aspects of alcohol-induced changes, including, for the first time, the behavioral effects of withdrawal from alcohol and neurochemical responses to alcohol. For example, withdrawal from alcohol abolished shoaling and increased dopamine and 3,4-dihydroxyphenylacetic acid in AB but not in SF fish. The findings show that, first, acute and chronic alcohol induced changes are quantifiable with automated behavioral paradigms; second, robust neurochemical changes are also detectable; and third, genetic factors influence both alcohol-induced behavioral and neurotransmitter level changes. Although the causal relationship underlying the alcohol-induced changes in behavior and neurochemistry is speculative at this point, the results suggest that zebrafish will be a useful tool for the analysis of the biological mechanisms of alcohol-induced functional changes in the adult brain.
Gerlai, R.; Chatterjee, D.; Pereira, T.; Sawashima, T.; Krishnannair, R.
Involvement of AMPK in Alcohol Dehydrogenase Accentuated Myocardial Dysfunction Following Acute Ethanol Challenge in Mice
ObjectivesBinge alcohol drinking often triggers myocardial contractile dysfunction although the underlying mechanism is not fully clear. This study was designed to examine the impact of cardiac-specific overexpression of alcohol dehydrogenase (ADH) on ethanol-induced change in cardiac contractile function, intracellular Ca2+ homeostasis, insulin and AMP-dependent kinase (AMPK) signaling.MethodsADH transgenic and wild-type FVB mice were acutely challenged with ethanol (3 g\\/kg\\/d, i.p.)
Rui Guo; Glenda I. Scott; Jun Ren; Sudha Agarwal
Prolonged hepatitis caused by cytomegalovirus and non-alcoholic steatohepatitis in 16-year-old obese boy
Recently, the prevalence of non-alcoholic steatohepatitis (NASH) has been increasingly reported in patients with type 2 diabetes and obesity. NASH exists not only in adults but also in children. We report on an 16-year-old boy with prolonged hepatitis associated with NASH after cytomegalovirus hepatitis. Increased transaminase levels recovered in parallel to his weight reduction. Conclusion:Clinicians should be aware of the
Tatsuo Kanda; Osamu Yokosuka; Yutaka Suzuki
Acute viral hepatitis in the United States-Mexico border region: data from the Border Infectious Disease Surveillance (BIDS) Project, 2000-2009.
Little is known about the characteristics of acute viral hepatitis cases in the United States (US)-Mexico border region. We analyzed characteristics of acute viral hepatitis cases collected from the Border Infectious Disease Surveillance Project from January 2000-December 2009. Over the study period, 1,437 acute hepatitis A, 311 acute hepatitis B, and 362 acute hepatitis C cases were reported from 5 Mexico and 2 US sites. Mexican hepatitis A cases most frequently reported close personal contact with a known case, whereas, US cases most often reported cross-border travel. Injection drug use was common among Mexican and US acute hepatitis B and C cases. Cross-border travel during the incubation period was common among acute viral hepatitis cases in both countries. Assiduous adherence to vaccination and prevention guidelines in the US is needed and strategic implementation of hepatitis vaccination and prevention programs south of the border should be considered. PMID:22447176
Spradling, Philip R; Xing, Jian; Phippard, Alba; Fonseca-Ford, Maureen; Montiel, Sonia; Guzmßn, Norma Luna; Campuzano, Roberto Vßzquez; Vaughan, Gilberto; Xia, Guo-liang; Drobeniuc, Jan; Kamili, Saleem; Cortķs-Alcalß, Ricardo; Waterman, Stephen H
Animated bird silhouette above the tank: Acute alcohol diminishes fear responses in zebrafish
Alcohol dependence and alcohol abuse represent major unmet medical needs. The zebrafish is considered to be a promising vertebrate species with which the effects of alcohol on brain function and behavior and the mechanisms underlying these effects may be studied. Alcohol is known to induce alterations in motor function as well as fear and anxiety. Here we present a recently developed fear paradigm in which we employ an animated (moving) image of a bird silhouette. We measure the effect of acute alcohol administration (dose range employed: 0.00 ¢ 0.75 vol/vol percentage, bath exposure for 60 minutes) on the behavioral responses of zebrafish. We test these responses during a pre-stimulus, stimulus and post-stimulus period of the task using both a video-tracking and an observation based quantification method. The fear inducing stimulus was found to decrease the distance of the zebrafish from the bottom of the tank, to increase number of erratic movements, and to increase the number of jumps in alcohol exposed fish (versus control fish). Alcohol attenuated these fear responses in a dose dependent manner. In addition, alcohol decreased general activity at the highest dose, an effect that was independent of the presentation of the stimulus. We discuss the similarities and differences between observation and video-tracking based results and conclude that fear paradigms will be useful in revealing alcohol induced functional changes in the brain of zebrafish.
Luca, Ruxandra M.; Gerlai, Robert
Effect of acute and chronic alcohol abuse on pain management in a trauma center
The proper management of acute pain has been identified as a primary indicator of quality assurance in US trauma centers. Nearly half of all trauma patients are injured while intoxicated and 75% of these patients have chronic alcohol problems. The management of pain caused by injuries in patients with alcohol problems poses unique challenges. Biases exist regarding the crosstolerance effects of ethanol and opioids and the pain thresholds of patients with substance abuse histories. The purpose of this review is to examine some of the factors that inform our decisions of how to manage acute pain in this population and to review the empirical evidence that exists.
Askay, Shelley Wiechman; Bombardier, Charles H; Patterson, David R
Drinking and future thinking: acute effects of alcohol on prospective memory and future simulation
BackgroundĀĀIt has recently been shown that acute alcohol globally impairs æprospective memoryÆ (PM)Śremembering to do something in the\\u000a future (Leitz et al. in Psychopharmacology 205:379¢387, 2009). In healthy, sober individuals, simulating future events at encoding enhances PM performance.\\u000a \\u000a \\u000a \\u000a AimsĀĀWe therefore aimed to determine if future event simulation could attenuate the impairing effects of acute alcohol on PM.\\u000a \\u000a \\u000a \\u000a MethodsĀĀUsing a double-blind
Theadora Paraskevaides; Celia J. A. Morgan; Julie R. Leitz; James A. Bisby; Peter G. Rendell; H. Valerie Curran
Pancreatic Damage after the First Episode of Acute Alcoholic Pancreatitis and Its Association with the Later Recurrence Rate
Background: Acute alcoholic pancreatitis (AAP) recurs in up to half of the patients, continuous alcohol consumption being an important risk factor. Changes in pancreatic function and morphology after acute pancreatitis have been characterized previously, but their association with later recurrences has not been adequately studied. Patients and Methods: In this prospective follow-up study, the pancreatic function of 54 patients (47
Hanna Pelli; Riitta Lappalainen-Lehto; Anneli Piironen; Satu Jõrvinen; Juhani Sand; Isto Nordback
Persistent Hepatitis E Virus Genotype 4 Infection in a Child With Acute Lymphoblastic Leukemia
Introduction: In general, the hepatitis E virus (HEV) causes acute, self-limiting hepatitis. Prolonged and chronic infections caused by HEV genotype 3 have been found in some immunosuppressed patients in developed countries. Case Presentation: Here we report a Chinese boy with acute lymphoblastic leukemia, who developed hepatitis E during a period of intensive chemotherapy. Twenty months after the initial infection, HEV viremia was reappeared in the patient, with detectable anti-HEV IgM and IgG and modestly elevated serum transaminases. Sequence analysis of the viral RNAs revealed the reactivation of the HEV genotype 4d strain, indicating viral persistence in the patient. Conclusions: To our knowledge, this is the first chronic case confirmed by the prolonged presence of HEV RNA in china. It is also the first reported persistent hepatitis E infection caused by HEV genotype 4.
Geng, Yansheng; Zhang, Hongxin; Huang, Weijin; J Harrison, Tim; Geng, Kunjing; Li, Zhuo; Wang, Youchun
Acute alcohol effects on attentional bias in heavy and moderate drinkers.
Heavy drinkers show an increased attentional bias to alcohol-related stimuli compared to moderate drinkers, and this bias is thought to promote motivation for alcohol consumption (Field & Cox, 2008). Studies have begun to examine acute alcohol effects on attentional bias; however, little is known regarding how these effects might differ based on drinker type. Further, the degree to which attentional bias in response to alcohol is associated with excessive alcohol consumption remains unexplored. For the current study, 20 heavy drinkers and 20 moderate drinkers completed a visual probe task in response to placebo and two active doses of alcohol (0.45g/kg and 0.65g/kg). Participants' eye-movements were monitored and attentional bias was calculated as the difference in time spent focused on alcohol compared to neutral images. Participants' alcohol consumption was assessed by a timeline follow-back calendar and a laboratory ad lib consumption task. Results showed that heavy drinkers displayed significantly greater attentional bias than did moderate drinkers following placebo. However, heavy drinkers displayed a dose-dependent decrease in attentional bias following alcohol, whereas the drug had no effect in moderate drinkers. Individual differences in attentional bias under placebo were strongly associated with both self-reported and laboratory alcohol consumption, yet bias following alcohol administration did not predict either measure of consumption. These findings suggest that attentional bias is strongest before a drinking episode begins. As such, an attentional bias might be most influential in terms of initiation of alcohol consumption, and less of a factor in promoting continued consumption within the drinking episode. PMID:22732051
Weafer, Jessica; Fillmore, Mark T
Glucocorticoids are ineffective in alcoholic hepatitis: a meta-analysis adjusting for confounding variables.
The aim of this study was to perform a meta-analysis of controlled clinical trials of glucocorticoid treatment in clinical alcoholic hepatitis, adjusting for prognostic variables and their possible interaction with therapy, because these trials have given appreciably different results. Weighted logistic regression analysis was applied using the summarised descriptive data (for example, % with encephalopathy, mean bilirubin value) of the treatment and control groups of 12 controlled trials that gave this information. Despite evidence of publication bias favouring glucocorticoid treatment, its overall effect on mortality was not statistically significant (p = 0.20)--the relative risk (steroid/control) was 0.78 (95% confidence intervals 0.51, 1.18). There was indication of interaction between glucocorticoid therapy and gender, but not encephalopathy. Thus, the effect of glucocorticoid treatment may be different (beneficial or harmful) in special patient subgroups. These results do not support the routine use of glucocorticoids in patients with alcoholic hepatitis, including those with encephalopathy. Whether other subgroups may benefit needs further investigation using the individual patient data from the published trials and testing in new randomised trials.
Christensen, E; Gluud, C
Dose-dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa
To determine if the clearance of hepatitis C genotype 1 virus (HCV) is dependent on the dose of interferon alfa-2b (IFN-?2b), the acute clearance of HCV after a single dose of either 3, 5, or 10 mIU of IFN-? was compared in patients with chronic hepatitis C. HCV-RNA levels following IFN-? administration were measured. At 24 hours, mean percentage serum
NP Lam; AU Neumann; Gretch; TE Wiley; AS Perelson; TJ Layden
Acute hepatitis C infection in a renal transplant recipient: primacy of the liver or kidney?
We present a case where a renal transplant recipient contracted chronic hepatitis C virus (HCV) infection post-transplantation. The disease progressed and deteriorated leading to fibrosing cholestatic hepatitis that mandated treatment. Treatment with pegylated interferon ?-2a and ribavirin was successful in salvaging the liver and eradicating the virus but as a consequence lead to treatment-resistant acute rejection and loss of the renal allograft. PMID:24907214
Althaf, Mohammed Mahdi; Abdelsalam, Mohamed Said; Rashwan, Mohamed; Nadri, Quaid
Acute hypoxia and cytochrome P450¢mediated hepatic drug metabolism in humans
Objective: Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes.Methods: Twelve healthy subjects who lived at sea level were exposed to altitude-induced hypoxia for 7 days at 4559 m above sea level. Hepatic CYP enzyme activity was measured before departure, at 24 and 96 hours after arrival to high-altitude location,
Gesche J³rgens; Hanne Rolighed Christensen; Kim Br°sen; Jesper Sonne; Steffen Loft; Niels Vidiendal Olsen
Early acute hepatitis with parenteral amiodarone: a toxic effect of the vehicle?
A 72 year old white man developed acute hepatic impairment and renal failure within 24 hours of starting intravenous amiodarone for paroxysmal ventricular tachycardia. After normal initial investigations, there was a noticeable rise in serum transaminases as well as an increase in clotting times, a decrease in renal function and a thrombocytopenia. These changes returned to normal within seven days of withdrawal of the drug without specific treatment, and the patient was later treated with oral amiodarone without any further evidence of hepatotoxicity. Intravenous amiodarone has been implicated in acute hepatic disease on four previous occasions, but it is suggested that polysorbate 80, an organic surfactant added to the intravenous infusion, is a more likely cause of this complication. Similar reactions have been described with polysorbate 80 in association with the 'E-ferol' syndrome in infants. The occurrence of acute hepatic impairment with intravenous amiodarone does not necessarily preclude the use of this drug by mouth.
Rhodes, A; Eastwood, J B; Smith, S A
Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States
SUMMARY. The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV- ALF) in the US. Clinical and laboratory features of con- secutive patients with HBV-ALF from the US ALF Study Group were
C.-T. Wai; R. J. Fontana; J. Polson; M. Hussain; A. O. Shakil; S.-H. Han; T. J. Davern; W. M. Lee; A. S.-F Lok
Hepatitis A-induced diabetes mellitus, acute renal failure, and liver failure.
A 38-year-old otherwise healthy man presented with hepatic failure (aspartate aminotransferase of 7212 U/L, alanine aminotransferase of 6629 U/L, total and direct bilirubin of 10.7 mg/dL) and acute renal failure (creatinine of 11.6 mg/dL and blood urea nitrogen of 42 mg/dL), which required hemodialysis when the creatinine increased to 21 mg/dL, with a blood urea nitrogen of 115 mg/dL, and the patient became oliguric. On admission, this patient also had a lipase of 1833 U/L, amylase of 211 U/L, glucose of 210 mg/dL, and reactive IgM antibody for acute hepatitis A. The hepatitis and acute renal failure resolved in 3 months, but this patient continues to have type II diabetes mellitus 7 years after the hepatitis A infection. This case illustrates that hepatitis A infection may be severe with liver failure, acute renal failure, and permanent diabetes mellitus as sequale of this infection. PMID:10372844
Vesely, D L; Dilley, R W; Duckworth, W C; Paustian, F F
Effector T cells immune reactivity among patients with acute hepatitis E.
Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis in several developing countries. Information on cellular immune responses during acute hepatitis E is limited. We therefore studied peripheral blood mononuclear cells (PBMCs) from patients with acute hepatitis E and healthy adult subjects who lacked anti-HEV antibodies for enumeration of various T-cell subsets using flow cytometry and to assess HEV-specific T effector cell responses using interferon-gamma ELISPOT assays. The patients showed increased numbers of CD8(+) cells and CD4(+) CD8(+) cells compared with healthy controls. In addition, the proportion of PBMCs that produced interferon-gamma in response to recombinant HEV open reading frame (ORF) 2 and ORF 3 proteins were found to be higher in patients than in healthy controls. Using pools of 15-mer overlapping peptides corresponding to these recombinant proteins, the immunodominant regions in these proteins for interferon-gamma-producing cells were mapped to regions corresponding to amino acids 181-249 and 301-489 of HEV ORF2 protein. These data provide evidence for the activation of effector T cells during acute hepatitis E. These responses may play a role in viral clearance from the host in patients with HEV infection. PMID:21914082
Husain, M M; Aggarwal, R; Kumar, D; Jameel, S; Naik, S
Case-control study to evaluate risk factors for acute hepatitis B virus infection in Egypt.
Hepatitis B virus (HBV) infection is a significant health problem in Egypt. To better define risk factors associated with HBV transmission, we conducted a case-control study among patients admitted with acute hepatitis to an infectious disease hospital in Cairo. A total of 60 cases and 120 controls were interviewed about various exposures within 6 months prior to admission. Univariate analysis revealed HBV case-patients were more likely to report providing injections to relatives or friends, injecting drug use, exposure to a household contact with hepatitis, exposure to invasive medical procedures and being in the military. Efforts should be made to implement strict infection control standards in Egypt. PMID:20214150
Talaat, M; Radwan, E; El-Sayed, N; Ismael, T; Hajjeh, R; Mahoney, F J
[Comparative study of hemostatic changes in acute viral hepatitis and terminal cirrhosis].
Twenty patients with severe hepatic failure and fatal evolution, in whom hemostatic parameters were studied are presented. Eleven had fulminant acute viral hepatitis (FVH) and nine had liver cirrhosis. Hepatic parenchymal failure was followed by altered coagulation factors. In FVH major disturbances were detected in factors II, V, VII - X. In our cirrhotic patients factor alterations were moderated. In spite of these differences the percentage of bleeding patients was similar in both groups. Prothrombin time plus tromboplastine partial time (KPTT) are useful prognostic complements for these two entities. PMID:7185233
Lemberg, A; Bengochea, L; Pierangeli, N
MnSOD Overexpression Prevents Liver Mitochondrial DNA Depletion after an Alcohol Binge but Worsens This Effect after Prolonged Alcohol Consumption in Mice
Both acute and chronic alcohol consumption increase reactive oxygen species (ROS) formation and lipid peroxidation, whose products damage hepatic mitochondrial DNA (mtDNA). To test whether manganese superoxide dismutase (MnSOD) overexpression modulates acute and chronic alcohol-induced mtDNA lesions, transgenic MnSOD-overexpressing (TgMnSOD+++) mice and wild-type (WT) mice were treated by alcohol, either chronically (7 weeks in drinking water) or acutely (single intragastric
Abdellah Mansouri; Arige Tarhuni; Isabelle Larosche; Florence Reyl-Desmars; Christine Demeilliers; Franńoise Degoul; Pierre Nahon; Angela Sutton; Richard Moreau; Bernard Fromenty; Dominique Pessayre
Pioglitazone, quercetin and hydroxy citric acid effect on hepatic biomarkers in Non Alcoholic Steatohepatitis
Background: Non alcoholic steatohepatitis (NASH), severe form of diseases belonging to the spectrum of the Non alcoholic fatty liver disease (NAFLD). It is an asymptomatic disease which leads to fibrosis and finally to cirrhosis, an end stage liver disease. Objective: To study the effect of pioglitazone, quercetin and hydroxy citric acid on hepatic biomarkers and various biochemical parameters in experimentally induced non alcoholic steatohepatitis (NASH). Materials and Methods: Male Wister rats were divided into 8 groups. The activities of alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and ?-Glutamyl Transferase (GGT) were assayed in serum. The levels of various other biochemical parameters such as serum albumin, total bilirubin, creatinine, urea, uric acid and glucose were also estimated in experimental NASH. Results: The NASH group produced severe liver injury by significantly increasing the serum levels of ALT, AST, GGT and LDH compared with that of the control. However, the experimental NASH rats treated with pioglitazone, with quercetin and with hydroxy citric acid showed an obvious decrease in ALT, AST, GGT and LDH levels when compared with that of NASH induced group. A significant increase in the levels of albumin, creatinine, urea, uric acid, glucose and total bilirubin was noticed in experimentally induced NASH group (group 2) when compared to rats in control group (group 1). Conclusion: It could be inferred from this study that, pioglitazone, quercetin and hydroxy citric acid may afford protection to the liver against NASH, as evidenced by the results of this study on the levels of various biochemical parameters such as glucose, urea, uric acid, creatinine and bilirubin. Whereas from the results of hepatic marker enzymes, it is evident that optimal protection was observed after quercetin treatment against experimental NASH whereas pioglitazone and hydroxy citric acid also confers protection to some extent against NASH.
Surapaneni, Krishna Mohan; Jainu, Mallika
Reduced Acute Recovery from Alcohol Impairment in Adults with ADHD
Rationale Prior research has found that adults with attention-deficit/hyperactivity disorder (ADHD) show increased sensitivity to the impairing effects of alcohol (Weafer et al. 2009). However, these studies have focused exclusively on the ascending limb of the blood alcohol concentration (BAC) curve, and it is unclear whether these adults continue to show increased sensitivity during the later phase of the dose as BAC is declining. Objective This study tested the hypothesis that those with ADHD would display increased response to alcohol during the ascending limb of the BAC curve and less recovery from the impairing effects during the descending limb. Methods Adult social drinkers with ADHD and control adults completed measures of motor coordination, reaction time, and subjective intoxication twice following 0.64 g/kg alcohol and placebo. The measures were administered during the ascending limb of the BAC curve and again during the descending limb. Results During the ascending limb, alcohol reduced motor coordination, slowed reaction time (RT), and increased self-reports of subjective intoxication. Those with ADHD displayed greater impairment of motor coordination compared with controls. During the descending limb, controls reported diminished subjective intoxication and showed recovery from the impairing effects of alcohol on both their motor coordination and their RT. Those with ADHD showed reduced subjective intoxication and faster RT during this time, but they did not recover motor control. Conclusions The protracted time course of motor impairment in adults with ADHD despite reductions in subjective intoxication may contribute to poor decision making and diminished behavioral control in this group.
Roberts, Walter; Milich, Richard; Fillmore, Mark T.
Ferritin L and ferritin H are differentially located within hepatic and extra hepatic organs under physiological and acute phase conditions
Ferritin L (FTL) and Ferritin H (FTH) subunits are responsible for intercellular iron storage. We previously reported increasing amounts of liver cytoplasmic and nuclear iron content during acute phase response (APR). Aim of the present study is to demonstrate intracellular localization of ferritin subunits in liver compared with extra hepatic organs of rat under physiological and acute phase conditions. Rats were administered turpentine-oil (TO) intramuscularly to induce a sterile abscess (acute-phase-model) and sacrificed at different time points. Immunohistochemistry was performed utilizing horse-reddish-peroxidise conjugated secondary antibody on 4?m thick section. Liver cytoplasmic and nuclear protein were used for Western blot analysis. By means of immunohistology, FTL was detected in cytoplasm while a strong nuclear positivity for FTH was evident in the liver. Similarly, in heart, spleen and brain FTL was detected mainly in the cytoplasm while FTH demonstrated intense nuclear and a weak cytoplasmic expression. Western blot analysis of cytoplasmic and nuclear fractions from liver, heart, spleen and brain further confirmed mainly cytoplasmic expression of FTL in contrast to the nuclear and cytoplasmic expression of FTH. The data presented demonstrate the differential localization of FTL and FTH within hepatic and extra hepatic organs being FTL predominantly in the cytoplasm while FTH predominantly in nucleus.
Ahmad, Shakil; Moriconi, Federico; Naz, Naila; Sultan, Sadaf; Sheikh, Nadeem; Ramadori, Giuliano; Malik, Ihtzaz Ahmed
Hepatitis E Virus Quasispecies and the Outcome of Acute Hepatitis E in Solid-Organ Transplant Patients
Hepatitis E virus (HEV) infections are responsible for chronic hepatitis in immunocompromised patients, and this can evolve to cirrhosis. Like all RNA viruses, HEV exists as a mixture of heterogeneous viruses defining quasispecies. The relationship between the genetic heterogeneity described as a quasispecies, cytokine secretion, and the outcome of acute hepatitis in immunocompromised patients remains to be elucidated. We cloned and sequenced the region encoding the M and P capsid domains of HEV from eight solid-organ transplant (SOT) patients with acute HEV infection who subsequently cleared the virus and from eight SOT patients whose infection became chronic. We analyzed the cytokines and chemokines in the sera of these SOT patients by multianalyte profiling. The nucleotide sequence entropy and genetic distances were greater in patients whose infections became chronic. A lower Ka/Ks ratio was associated with the persistence of HEV. The patients who developed chronic infection had lower serum concentrations of interleukin-1 (IL-1) receptor antagonist and soluble IL-2 receptor. Increased concentrations of the chemokines implicated in leukocyte recruitment to the liver were associated with persistent infection. Those patients with chronic HEV infection and progressing liver fibrosis had less quasispecies diversification during the first year than patients without liver fibrosis progression. Great quasispecies heterogeneity, a weak inflammatory response, and high serum concentrations of the chemokines involved in leukocyte recruitment to the liver in the acute phase were associated with persistent HEV infection. Slow quasispecies diversification during the first year was associated with rapidly developing liver fibrosis.
Lhomme, Sebastien; Abravanel, Florence; Dubois, Martine; Sandres-Saune, Karine; Rostaing, Lionel; Kamar, Nassim
Acute Ethanol Effects on Brain Activation in Low- and High-Level Responders to Alcohol
Background A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk for alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption. Methods 30 matched high- and low-LR pairs (N=60 healthy young adults) were recruited from the University of California, San Diego and administered a structured diagnostic interview and laboratory alcohol challenge followed by two fMRI sessions under placebo and alcohol conditions, in randomized order. Task performance and BOLD response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task was examined across 120 fMRI sessions. Results Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p<.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity. Conclusions Alcohol had differential effects on brain activation for low and high LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR, and identify brain regions that may be associated with the low LR response.
Trim, Ryan S.; Simmons, Alan N.; Tolentino, Neil J.; Hall, Shana A.; Matthews, Scott C.; Robinson, Shannon K.; Smith, Tom L.; Padula, Claudia B.; Paulus, Martin P.; Tapert, Susan F.; Schuckit, Marc A.
Acute Alcohol Effects on Repetition Priming and Word Recognition Memory with Equivalent Memory Cues
ERIC Educational Resources Information Center
Acute alcohol intoxication effects on memory were examined using a recollection-based word recognition memory task and a repetition priming task of memory for the same information without explicit reference to the study context. Memory cues were equivalent across tasks; encoding was manipulated by varying the frequency of occurrence (FOC) of wordsģ
Ray, Suchismita; Bates, Marsha E.
The Effects of Acute Alcohol Intoxication on Person Memory: The Stereotypical Drunk
Research has suggested that acute alcohol intoxication disrupts cognitive function- ing by reducing the availability of executive resources for person perception. The present study tested the prediction that this effect would increase stereotype ap- plication during impression formation by reducing the encoding of nonstereotypical information. Participants were instructed to complete an impression-formation task following consumption of low, medium, or high
Sheila J. Cunningham; Alan B. Milne; John R. Crawford
Cytochrome P450 2E1 inhibition prevents hepatic carcinogenesis induced by diethylnitrosamine in alcohol-fed rats
Chronic alcohol ingestion increases hepatic cytochrome P450 2E1 (CYP2E1), which is associated with hepatocarcinogenesis. We investigated whether treatment with chlormethiazole (CMZ), a CYP2E1 inhibitor, protects against alcohol-associated hepatic carcinogenesis in rats. Rats were fed either an ethanol liquid diet or a non-ethanol liquid diet, with or without CMZ for one and ten months. A single intraperitoneal injection of diethylnitrosamine (DEN, 20 mg/kg) was given to initiate hepatic carcinogenesis. CYP2E1 expression, inflammatory proteins, cell proliferation, protein-bound 4-HNE, etheno-DNA adducts, 8-hydroxy-2'-deoxyguanosine (8-OHdG), retinoid concentrations, and hepatic carcinogenesis were examined. Ethanol feeding for 1 month with DEN resulted in significantly increased hepatic CYP2E1 levels and increased nuclear accumulation of NF-?B protein and TNF-? expression, which were associated with increased cyclin D1 expression and p-GST positive altered hepatic foci. All of these changes induced by ethanol feeding were significantly inhibited by the one month CMZ treatment. At 10-months of treatment, hepatocellular adenomas were detected in ethanol-fed rats only, but neither in control rats nor in animals receiving ethanol and CMZ. The 8-OHdG formation was found to be significantly increased in ethanol fed animals and normalized with CMZ treatment. In addition, alcohol-reduced hepatic retinol and retinoic acid concentrations were restored by CMZ treatment to normal levels in the rats at 10 months of treatment. These data demonstrate that the inhibition of ethanol-induced CYP2E1 as a key pathogenic factor can counteract the tumor-promoting action of ethanol by decreasing TNF-? expression, NF-?B activation, and oxidative DNA damage as well as restoring normal hepatic levels of retinoic acid in DEN-treated rats.
Ye, Qinyuan; Lian, Fuzhi; Chavez, Pollyanna R.G.; Chung, Jayong; Ling, Wenhua; Qin, Hua; Seitz, Helmut K.
Computed tomography findings for predicting severe acute hepatitis with prolonged cholestasis
AIM: To evaluate the significance of computed tomography (CT) findings in relation to liver chemistry and the clinical course of acute hepatitis. METHODS: Four hundred and twelve patients with acute hepatitis who underwent enhanced CT scanning were enrolled retrospectively. Imaging findings were analyzed for the following variables: gallbladder wall thickness (GWT), arterial heterogeneity, periportal tracking, number and maximum size of lymph nodes, presence of ascites, and size of spleen. The serum levels of alanine aminotransferase, alkaline phosphatase, bilirubin, albumin, and prothrombin time were measured on the day of admission and CT scan, and laboratory data were evaluated every 2-4 d for all subjects during hospitalization. RESULTS: The mean age of patients was 34.4 years, and the most common cause of hepatitis was hepatitis A virus (77.4%). The mean GWT was 5.2 mm. The number of patients who had findings of arterial heterogeneity, periportal tracking, lymph node enlargement > 7 mm, and ascites was 294 (80.1%), 348 (84.7%), 346 (84.5%), and 56 (13.6%), respectively. On multivariate logistic regression, male gender [odds ratio (OR) = 2.569, 95%CI: 1.477-4.469, P = 0.001], toxic hepatitis (OR = 3.531, 95%CI: 1.444-8.635, P = 0.006), level of albumin (OR = 2.154, 95%CI: 1.279-3.629, P = 0.004), and GWT (OR = 1.061, 95%CI: 1.015-1.110, P = 0.009) were independent predictive factors for severe hepatitis. The level of bilirubin (OR = 1.628, 95%CI: 1.331-1.991, P < 0.001) and GWT (OR = 1.172, 95%CI: 1.024-1.342, P = 0.021) were independent factors for prolonged cholestasis in multivariate analysis. CONCLUSION: In patients with acute hepatitis, GWT on CT scan was an independent predictor of severe hepatitis and prolonged cholestasis.
Park, Sang Jung; Kim, Jin Dong; Seo, Yeon Seok; Park, Beom Jin; Kim, Min Ju; Um, Soon Ho; Kim, Chang Ha; Yim, Hyung Joon; Baik, Soon Koo; Jung, Jin Yong; Keum, Bora; Jeen, Yoon Tae; Lee, Hong Sik; Chun, Hoon Jai; Kim, Chang Duck; Ryu, Ho Sang
Superselective arterial embolisation with a liquid polyvinyl alcohol copolymer in patients with acute gastrointestinal haemorrhage
ObjectivesĀĀTo evaluate the results of emergency embolisation in acute arterial bleeding of the gastrointestinal tract with a liquid polyvinyl\\u000a alcohol copolymer from two centres.\\u000a \\u000a \\u000a \\u000a \\u000a MethodsĀĀWe retrospectively analysed 16 cases (15 patients) of acute arterial bleeding of the gastrointestinal tract where emergency\\u000a embolotherapy was performed by using the copolymer when acute haemorrhage was not treatable with endoscopic techniques alone.\\u000a Cause of
Markus Lenhart; Christian Paetzel; Michael Sackmann; Hans Schneider; Ernst Michael Jung; Andreas G. Schreyer; Stefan Feuerbach; Niels Zorger
Infection and the progression of hepatic encephalopathy in acute liver failure
Background & Aims:Progression of hepatic encephalopathy (HE) is a major determinant of outcome in acute liver failure (ALF). Our aim was to identify predictive factors of worsening HE, including the relation of encephalopathy with the systemic inflammatory response (SIRS) and infection. Methods:We included 227 consecutive patients with stage I-II HE prospectively enrolled in the U.S. Acute Liver Failure Study. Univariate
Javier Vaquero; Julie Polson; Chuhan Chung; Irene Helenowski; Frank V. Schiodt; Joan Reisch; William M. Lee; Andres T. Blei
Alcohol Screening Scores and 90 Day Outcomes in Patients with Acute Lung Injury
Objective The effects of excess alcohol consumption (alcohol misuse) on outcomes in patients with acute lung injury (ALI) have been inconsistent, and there are no studies examining this association in the era of low tidal volume ventilation and a fluid conservative strategy. We sought to determine whether validated scores on the Alcohol Use Disorders Identification Test (AUDIT) that correspond to past year abstinence (zone 1), low-risk drinking (zone 2), mild to moderate alcohol misuse (zone 3), and severe alcohol misuse (zone 4) are associated with poor outcomes in patients with ALI. Design Secondary analysis. Setting The Acute Respiratory Distress Syndrome (ARDS) network, a consortium of 12 university centers (44 hospitals) dedicated to the conduct of multi-center clinical trials in patients with acute lung injury. Subjects Patients meeting consensus criteria for ALI enrolled in one of three recent ARDS network clinical trials. Interventions None Measurements and Main Results Of 1,133 patients enrolled in one of three ARDS network studies, 1,037 patients had an AUDIT score available for analysis. Alcohol misuse was common with 70 (7%) of patients having AUDIT scores in zone 3 and 129 (12%) patients in zone 4. There was a u-shaped association between validated AUDIT zones and death or persistent hospitalization at 90 days (34% in zone 1, 26% in zone 2, 27% in zone 3, 36% in zone 4; p < 0.05 for comparison of zone 1 to zone 2 and zone 4 to zone 2). In a multiple logistic regression model, there was a significantly higher odds of death or persistent hospitalization in patients in AUDIT zone 4 when compared to those in zone 2 (adjusted OR 1.70; 95% CI 1.00, 2.87; p = 0.048). Conclusions Severe, but not mild to moderate alcohol misuse is independently associated with an increased risk of death or persistent hospitalization at 90 days in ALI patients.
Clark, Brendan J.; Williams, Andre; Cecere, Laura M.; Bradley, Katharine A.; Macht, Madison; Moss, Marc; Burnham, Ellen L.
Alcohol Impairs Interferon Signaling and Enhances Full Cycle Hepatitis C Virus JFH-1 Infection of Human Hepatocytes
Alcohol drinking and hepatitis C virus (HCV) infection frequently coexist in patients with chronic liver disease. There is limited information, however, about the impact of alcohol on host cell innate immunity and full cycle replication of HCV. This study investigated whether alcohol impairs the intracellular innate immunity in human hepatocytes, promoting HCV infection and replication. Alcohol treatment of human hepatocytes before, during and after viral infection significantly enhanced full cycle HCV replication. Alcohol suppressed intracellular expression of type I interferons (IFN-?/?) in human hepatocytes. Investigation of the mechanisms responsible for the alcohol action revealed that alcohol inhibited the expression of the IFN regulatory factors (IRF-5 and IRF-7), and signal transducer and activator of transcription (STAT-1 and STAT-2), the key positive regulators in type I IFN signaling pathway. In addition, alcohol induced the expression of suppressors of cytokine signaling (SOCS-2 and SOCS-3), the key negative regulators of IFN-?/? expression. These in vitro findings suggest that alcohol, through modulating the expression of key regulators in IFN signaling pathway, inhibits type I IFN-based intracellular innate immunity in hepctocytes, which may contribute to the chronicity of HCV infection and the poor efficacy of IFN-?-based therapy.
Ye, Li; Wang, Shihong; Wang, Xu; Zhou, Yu; Li, Jieliang; Persidsky, Yuri; Ho, Wenzhe
Additive activation of hepatic NF-kB by ethanol and HBX or HCV core protein: involvement of TNF-a receptor I-independent and -dependent mechanisms
Alcohol consumption and viral hepatitis infection synergistically accelerate liver injury, but the underlying mechanism is not fully understood. Here we have examined the effects of ethanol on hepatitis B protein X (HBX)- or hepatitis C core protein (HCV core protein)-mediated activation of NF-?B, a critical signal in hepatic injury, regeneration, and tumor transformation. Acute ethanol or acetaldehyde exposure potentiates HBX
Won-Ho Kim; Feng Hong; Barbara Jaruga; Zongyi Hu; Saijun Fan; T. Jake Liang
Selenium dietary supplementation as a mechanism to restore hepatic selenoprotein regulation in rat pups exposed to alcohol.
Ethanol exposure during gestation and lactation decreases selenium (Se) intake, disrupting body Se balance and inducing oxidative stress in rat offspring. Selenium-supplemented diet (0.5 ppm) was administered to ethanol-exposed (20% v/v) dams during gestation and lactation. When the dams' pups were 21 days old, the pups' levels of the main hepatic selenoproteins glutathione peroxidase (GPx1 and GPx4) and selenoprotein P (SelP) were measured. The pups were divided into control (C), alcohol (A), control-selenium (CS), and alcohol-selenium (AS) groups. The purpose was to evaluate the effect of the selenium-supplemented diet on the levels of Se deposits present in the livers of their pups. Alcohol decreases hepatic Se deposits, GPx activity, and GPx1 expression; alcohol increases GPx4 and SelP expression. Se was measured by furnace graphite atomic absorption spectrometry, the antioxidant activity of GPx and concentration of hepatic phospholipids (PL) were determined by spectrophotometry, and the selenoprotein expressions were detected by Western blotting. Selenite treatment prevented alcohol's effects of diminishing the Se deposits, GPx activity, and GPx1 expression, while maintaining the high levels of the expression of GPx4 and SelP. These results suggest that depletion of hepatic Se levels in rat pups, caused by ethanol exposure to their dams, affects the synthesis of the 3 main hepatic selenoproteins in different ways, which is related to a decrease in GPx activity and PL concentration, and an increase in serum Se levels. Selenium supplementation to the dams increased the expression of GPx1, GPx4, and SelP in their pups. PMID:24113570
Jotty, Karick; Ojeda, M Luisa; Nogales, Fßtima; Murillo, M Luisa; Carreras, Olimpia
Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions
The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360░. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360░ for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360░ for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions.
Cavalcanti-Galdino, M.K.; da Silva, J.A.; Mendes, L.C.; dos Santos, N.A.; Simas, M.L.B.
Acute Inflammatory Bowel Disease Complicating Chronic Alcoholism and Mimicking Carcinoid Syndrome
We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient's condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome.
Ballo, Piercarlo; Dattolo, Pietro; Mangialavori, Giuseppe; Ferro, Giuseppe; Fusco, Francesca; Consalvo, Matteo; Chiodi, Leandro; Pizzarelli, Francesco; Zuppiroli, Alfredo
Differences in Acute Alcohol-Induced Behavioral Responses Among Zebrafish Populations
Background With the arsenal of genetic tools available for zebrafish, this species has been successfully used to investigate the genetic aspects of human diseases from developmental disorders to cancer. Interest in the behavior and brain function of zebrafish is also increasing as CNS disorders may be modeled and studied with this species. Alcoholism and alcohol abuse are among the most devastating and costliest diseases. However, the mechanisms of these diseases are not fully understood. Zebrafish has been proposed as a model organism to study such mechanisms. Characterization of alcoholÆs effects on zebrafish is a necessary step in this research. Methods Here, we compare the effects of acute alcohol (EtOH) administration on the behavior of zebrafish from 4 distinct laboratory-bred populations using automated as well as observation based behavioral quantification methods. Results Alcohol treatment resulted in significant dose-dependent behavioral changes but the dose¢response trajectories differed among zebrafish populations. Conclusions The results demonstrate for the first time a genetic component in alcohol responses in adult zebrafish and also show the feasibility of high throughput behavioral screening. We discuss the exploration and exploitation of the genetic differences found.
Gerlai, Robert; Ahmad, Fahad; Prajapati, Sonal
An acute psychosocial stressor increases drinking in non-treatment-seeking alcoholics
Rationale Although studies suggest that stress is an important reason for relapse in alcoholics, few controlled studies have been conducted to examine this assumption. Evidence of stress-potentiated drinking would substantiate this clinical observation and would contribute to the development of a model that would be valuable to alcohol treatment research. Objectives The hypothesis was tested that an acute psychosocial stressor, the Trier Social Stress Test (TSST), increases alcohol consumption in non-treatment-seeking alcoholics. Methods Seventy-nine alcohol-dependent participants (40 women) were randomly assigned to receive the TSST or a no-stress condition. Immediately afterward, all participants received an initial dose of their preferred alcoholic beverage to achieve a target blood alcohol concentration of 0.03 g/dl (to prime subsequent drinking in the laboratory). Participants then participated in a mock taste test of two glasses of beer. Primary dependent measures were whether s/he drank all of the beer available (yes/no) and total amount of beer consumed (milliliters). Results Stressed participants were twice as likely as non-stressed participants to drink all of the beer available, a significant effect. Although the stressed group drank more milliliters than the non-stressed group, this effect failed to reach significance, likely due to ceiling effects. There were no significant stress group ū gender effects on either outcome. Conclusions This study supports that stress-potentiated drinking is valid and can be modeled in a clinical laboratory setting.
Bacon, Amy K.; Randall, Patrick K.; Brady, Kathleen T.; See, Ronald E.
Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions.
The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360░. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360░ for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360░ for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions. PMID:24676473
Cavalcanti-Galdino, M K; da Silva, J A; Mendes, L C; dos Santos, N A; Simas, M L B
[Rare acute hepatitis in a female patient with hemochromatosis: a zoonosis?].
A 58-year-old female patient was transferred by her general practitioner with fatigue, nausea and icterus which had begun 2 weeks prior to admission. Laboratory results revealed acute hepatitis (ALAT [alanine aminotransferase] 3,871 U/l, ASAT [aspartate aminotransferase] 2,004 U/l, bilirubin 6.7 mg/dl, gamma-GT [gamma-glutamyl transferase] 503 U/l). The patient's medical history included genetic hemochromatosis (without cirrhosis). Hepatitis A to C, infection with herpesviruses or Leptospira interrogans were excluded by serologic and molecular biological tests. There was no diagnostic evidence for underlying autoimmune or additional metabolic liver disease. Due to a trip to Africa 5 months earlier, the patient was tested for hepatitis E, leading to positive anti-hepatitis E-IgM and negative anti-hepatitis E-IgG. PCR (polymerase chain reaction) detection of hepatitis E virus (HEV) was positive as well. In conclusion, acute HEV infection was diagnosed. After close reconsideration, the nonfitting incubation period precluded a travel-associated infection. Additionally, there was no evidence for current HEV infections within the patient's social environment, so that a zoonotic origin has to be discussed. PMID:20455055
Vetter, Stephan; Hartmann, Dirk; Jakobs, Ralf; Riemann, J³rgen F
Compromised function of natural killer cells in acute and chronic viral hepatitis.
Background.?Natural killer (NK) cells are an integral part of the innate immune system. They have been suggested to play an important role in both defense against viral hepatitis and the pathogenesis of other liver diseases. Methods.?NK cells from 134 individuals including patients with acute hepatitis B and C as well as chronic hepatitis B, C, and delta (D) patients were studied. Results.?Infection with viral hepatitis was associated with increased frequencies of NK cells in the peripheral blood; that NK cells showed a less activated phenotype and were compromised in cytolotytic function and cytokine production in all viral hepatitis infections: Hepatitis virus infections did not alter NK cell differentiation, and the activity and severity of liver disease were reflected by alterations of NK cell surface receptors as demonstrated by principal component analysis. Conclusion.?NK cell phenotypic and functional alterations can equally be observed in HBV, HCV, and HDV infections. Instead, patterns of NK cell alterations differ in acute and chronic infections. Thus, our data suggest a common mechanism in the alteration of NK cell phenotype and function with unique variations that depend on disease activity rather than virus-specific factors. PMID:24154737
Lunemann, Sebastian; Malone, David F G; Hengst, Julia; Port, Kerstin; Grabowski, Jan; Deterding, Katja; Markova, Antoaneta; Bremer, Birgit; Schlaphoff, Verena; Cornberg, Markus; Manns, Michael P; Sandberg, Johan K; Ljunggren, Hans-Gustaf; Bj÷rkstr÷m, Niklas K; Wedemeyer, Heiner
Acute Sterol O-Acyltransferase 2 (SOAT2) Knockdown Rapidly Mobilizes Hepatic Cholesterol for Fecal Excretion.
The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD), the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ?2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion. PMID:24901470
Marshall, Stephanie M; Gromovsky, Anthony D; Kelley, Kathryn L; Davis, Matthew A; Wilson, Martha D; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Rudel, Lawrence L; Brown, J Mark; Temel, Ryan E
Acute Sterol O-Acyltransferase 2 (SOAT2) Knockdown Rapidly Mobilizes Hepatic Cholesterol for Fecal Excretion
The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD), the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ?2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion.
Marshall, Stephanie M.; Gromovsky, Anthony D.; Kelley, Kathryn L.; Davis, Matthew A.; Wilson, Martha D.; Lee, Richard G.; Crooke, Rosanne M.; Graham, Mark J.; Rudel, Lawrence L.
To determine the hepatic and enal effects of acute exposure to inhaled epichlorohydrin (ECH), male F-344 rats were exposed either to 0 or to 100 ppm ECH by inhalation for 4 hours. epatic and renal toxicity-were assessed at the termination of exposure and on the first, second and ...
Acute hepatitis due to shen-min: a herbal product derived from Polygonum multiflorum.
Shen-Min is a herbal product sold as a supplement for women to enhance hair growth. It is widely available across Asia, Europe, and the United States and sold without prescription as a hair nutritional supplement. We describe a case of acute liver injury in a 28-year-old white woman who developed symptomatic hepatitis 8 weeks after starting Shen-Min. All other potential causes of acute hepatitis including viral, hypoxic/ischemic, metabolic, and autoimmune etiologies were excluded. The liver injury slowly resolved over 3 weeks after discontinuing the herbal product. Although the mechanism of Shen-Min hepatotoxicity is unknown, we suspect an idiosyncratic reaction because the patient developed a fine maculopapular rash, mild eosinophilia, and did not overdose. Shen-Min is a Chinese herbal product with a mixture of several plants and vitamins including Polygonum multiflorum, a root that has been previously associated with hepatotoxicity. Nonetheless to our knowledge this is the first reported case of herbal-induced hepatotoxicity in a patient taking Shen-Min per se. Clinicians taking care of patients with acute hepatitis of unclear etiology should be aware that the consumption of Shen-Min, a hair supplement widely available in the United States and Western countries might cause acute hepatitis. PMID:16917407
Cßrdenas, Andrķs; Restrepo, Juan Carlos; Sierra, Fernando; Correa, Gonzalo
Infection and the Progression of Hepatic Encephalopathy in Acute Liver Failure
Background & Aims: Progression of hepatic encephalop- athy (HE) is a major determinant of outcome in acute liver failure (ALF). Our aim was to identify predictive factors of worsening HE, including the relation of en- cephalopathy with the systemic inflammatory response (SIRS) and infection. Methods: We included 227 consec- utive patients with stage I-II HE prospectively enrolled in the U.S.
Hepatitis B Infection in Patients With Acute Liver Failure in the United States
Occult hepatitis B virus (HBV) infection has been re- ported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the preva- lence of precore and core promoter variants
Hepatitis B infection in patients with acute liver failure in the United States
Occult hepatitis B virus (HBV) infection has been reported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients
Eng-Kiong Teo; George Ostapowicz; Munira Hussain; William M. Lee; Robert J. Fontana; Anna S. F. Lok
Aminotransferase changes and acute hepatitis in patients with dengue fever: analysis of 1,585 cases
Introduction: Type 3 dengue virus caused an extensive epidemic in the state of Rio de Janeiro in summer 2002. In some of the patients, it was found in an atypical form with increased aminotransferase levels and acute hepatitis. Material and Methods: An analysis was made of 1,585 serologically confirmed dengue cases at the Dengue Reference Center in Campos dos Goytacazes,
Luiz Josķ de Souza; Josķ GalvŃo Alves; Rita Maria Ribeiro Nogueira; Carlos Gicovate Neto; Diogo Assed Bastos; Edno Wallace da Silva Siqueira; JoŃo Tadeu Damian Souto Filho; Thiago de Abreu Cezßrio; Carlos Eduardo Soares; Rodrigo da Costa Carneiro
Herpes simplex virus type 2 fulminant hepatitis after umbilical cord blood transplantation for acute myeloid leukemia.
This report describes a 41-year-old patient, who developed herpes simplex virus type 2 (HSV-2)-hepatitis after umbilical cord blood transplantation (CBT). The patient had received allogeneic bone marrow transplantation from an unrelated donor for acute myeloid leukemia (AML) not in remission. AML relapsed 18 months after the first transplantation, and CBT was performed. AML relapsed again 5 months later and the patient was given chemotherapy. Although there was no active chronic graft-versus-host disease, liver dysfunction appeared, and one week later, progressed to acute liver failure. Viral screening of blood by PCR including hepatitis B and C viruses, human immunodeficiency virus, Epstein-Barr virus, cytomegalovirus, herpes simplex virus type 1 and HSV-2 revealed elevation of HSV-2 (2.34ū10(4) copies/ml). We diagnosed the patient as having HSV-2 acute hepatitis, and initiated treatment with antiviral drugs (acyclovir, foscarnet) and plasma exchange. However, liver functions deteriorated rapidly, and the patient died on day 6 after the onset of acute liver failure. Although HSV hepatitis is very rare after allogeneic stem cell transplantation, it is rapidly progressive and associated with a high mortality rate. Thus, early diagnosis with prompt antiviral intervention is recommended. PMID:24975337
Yuasa, Mitsuhiro; Ishiwata, Kazuya; Sugio, Takeshi; Kaji, Daisuke; Ota, Hikari; Tsuji, Masanori; Yamamoto, Hisashi; Yamamoto, Go; Asano-Mori, Yuki; Uchida, Naoyuki; Izutsu, Koji; Taniguchi, Shuichi
RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice.
The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias. PMID:24821812
Yasuda, Makiko; Gan, Lin; Chen, Brenden; Kadirvel, Senkottuvelan; Yu, Chunli; Phillips, John D; New, Maria I; Liebow, Abigail; Fitzgerald, Kevin; Querbes, William; Desnick, Robert J
RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice
The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias.
Yasuda, Makiko; Gan, Lin; Chen, Brenden; Kadirvel, Senkottuvelan; Yu, Chunli; Phillips, John D.; New, Maria I.; Liebow, Abigail; Fitzgerald, Kevin; Querbes, William; Desnick, Robert J.
Persistence of acute infection with hepatitis B virus genotype A and treatment in Japan.
Among the 97 adult patients with acute hepatitis B who were admitted to the Toranomon Hospital in Metropolitan Tokyo during 28 years from 1976 to 2003, 31 (32%) were infected with hepatitis B virus (HBV) genotype A, nine (9%) with genotype B, 44 (45%) with genotype C, one (1%) each with genotypes E and F. HBV in the remaining 11 (11%) patients were untypeable. All the 31 patients with acute hepatitis B caused by HBV genotype A infection were male with a median age of 31 years, and 16 (52%) contracted infection through extramarital sexual contacts. The baseline HBV DNA level was higher in the seven (23%) patients in whom infection with HBV genotype A persisted than the remaining 24 (77%) with spontaneous resolution (median: >8.7 vs. 6.0 log genome equivalents/ml, P = 0.004). Persistent infection was more frequent in patients with maximum alanine aminotransferase <500 IU/L than > or =500 IU/L (83% [5/6] vs. 4% [1/25], P = 0.0001). Of the six patients with persistent HBV genotype A infection who received interferon and/or lamivuidine for treatment of chronic active hepatitis, three (50%) responded with the loss of hepatitis B e antigen (HBeAg); hepatitis B surface antigen (HBsAg) was cleared from serum in one patient who received interferon and lamivudine in sequence. HBV genotype A persisted along with HBeAg in the remaining three patients given antiviral therapy as well as another who was not treated. In conclusion, infection with HBV genotype A prevails in patients with acute hepatitis B in Japan where genotypes B and C are common, is often contracted sexually (16/31 [52%]) and tends to persist (7/31 [23%]). Infection was cleared in only one of the six (17%) patients who received antiviral therapy. PMID:15779048
Suzuki, Yoshiyuki; Kobayashi, Mariko; Ikeda, Kenji; Suzuki, Fumitaka; Arfase, Yasuji; Akuta, Norio; Hosaka, Tetsuya; Saitoh, Satoshi; Kobayashi, Masahiro; Someya, Takashi; Matsuda, Marie; Sato, Junko; Watabiki, Sachiyo; Miyakawa, Yuzo; Kumada, Hiromitsu
Acute hepatitis in a young woman with systemic lupus erythematosus: a diagnostic challenge.
A 48-year-old woman with systemic lupus erythematosus diagnosis was on naproxen, hidroxichloroquine and acetylsalicylic acid. She had self-suspended all medication and resumed 1 year later. Five days after the medication was resumed, she developed acute hepatitis, with biochemical hepatic cytolysis, hypergamaglobulinaemia and a serum antinuclear antibody titre of 1/2560. Idiopathic autoimmune hepatitis was considered, but drug-induced liver injury could not definitely be ruled out. Patient declined liver biopsy. Oral prednisolone was started. Within 3 months with prednisolone being tapered to 10 mg/day, a new flare occurred. Liver biopsy was performed and it favoured autoimmune hepatitis diagnosis. We discuss the diagnostic options and treatment approach in a patient with autoimmune disease and possible drug-induced liver injury who initially declined liver biopsy. PMID:23563681
Barosa, Rita; Ramos, LĒdia Roque; Fonseca, Cristina; Freitas, JoŃo
Monounsaturated fat decreases hepatic lipid content in non-alcoholic fatty liver disease in rats
AIM: To evaluate the effects of different types of dietary fats on the hepatic lipid content and oxidative stress parameters in rat liver with experimental non-alcoholic fatty liver disease (NAFLD). METHODS: A total of 32 Sprague-Dawley rats were randomly divided into five groups. The rats in the control group (n = 8) were on chow diet (Group 1), rats (n = 6) on methionine choline-deficient diet (MCDD) (Group 2), rats (n = 6) on MCDD enriched with olive oil (Group 3), rats (n = 6) on MCDD with fish oil (Group 4) and rats (n = 6) on MCDD with butter fat (Group 5). After 2 mo, blood and liver sections were examined for lipids composition and oxidative stress parameters. RESULTS: The liver weight/rat weight ratio increased in all treatment groups as compared with the control group. Severe fatty liver was seen in MCDD + fish oil and in MCDD + butter fat groups, but not in MCDD and MCDD + olive oil groups. The increase in hepatic triglycerides (TG) levels was blunted by 30% in MCDD + olive oil group (0.59 ▒ 0.09) compared with MCDD group (0.85 ▒ 0.04, p < 0.004), by 37% compared with MCDD + fish oil group (0.95 ▒ 0.07, p < 0.001), and by 33% compared with MCDD + butter group (0.09 ▒ 0.1, p < 0.01). The increase in serum TG was lowered by 10% in MCDD + olive oil group (0.9 ▒ 0.07) compared with MCDD group (1.05 ▒ 0.06). Hepatic cholesterol increased by 15-fold in MCDD group [(0.08 ▒ 0.02, this increment was blunted by 21% in MCDD + fish oil group (0.09 ▒ 0.02)]. In comparison with the control group, ratio of long-chain polyunsaturated fatty acids omega-6/omega-3 increased in MCDD + olive oil, MCDD + fish oil and MCDD + butter fat groups by 345-, 30- and 397-fold, respectively. In comparison to MCDD group (1.58 ▒ 0.08), hepatic MDA contents in MCDD + olive oil (3.3 ▒ 0.6), MCDD + fish oil (3.0 ▒ 0.4), and MCDD + butter group (2.9 ▒ 0.36) were increased by 108%, 91% and 87%, respectively (p < 0.004). Hepatic paraoxonase activity decreased significantly in all treatment groups, mostly with MCDD + olive oil group (-68%). CONCLUSION: Olive oil decreases the accumulation of triglyceride in the liver of rats with NAFLD, but does not provide the greatest antioxidant activity.
Hussein, Osamah; Grosovski, Masha; Lasri, Etti; Svalb, Sergio; Ravid, Uzi; Assy, Nimer
Alcohol use disorders affect millions of individuals worldwide. Alcohol consumption is directly associated with liver disease mortality and accounts for elevated social and economic costs. Alcoholic liver disease (ALD) may take the form of acute involvement (alcoholic hepatitis) or chronic liver disease (steatosis, steatohepatitis, fibrosis and cirrhosis). The severity and prognosis of alcohol-induced liver disease depends on the amount, pattern and duration of alcohol consumption, as well as on the presence of liver inflammation, diet, nutritional status and genetic predisposition of an individual. While steatosis is an almost completely benign disease, liver cirrhosis is associated with marked morbidity, mortality and life expectancy shortening. The median survival of patients with advanced cirrhosis is 1-2 years. Severe acute alcoholic hepatitis (AH) is associated with mortality as high as 50%. It has been managed with corticoids, pentoxifylline and enteral nutrition, although evidence based data are still conflicting. Some author suggest that pentoxifylline could be a better first-line treatment in patients with severe AH. Absolute abstinence is a basic condition for any treatment of acute or chronic ALD, the other therapeutical procedure being of a supportive nature and questionable significance. Acamprosate appears to be an effective treatment strategy for supporting continuous abstinence in alcohol dependent patients. Patients with advanced liver cirrhosis who demonstrably abstain can be considered for liver transplantation, which leads to a markedly prolonged life expectancy. The crucial step in ALD prevention is in the prevention of alcohol abuse, whereas the prevention of liver injury in active alcohol abusers is not clinically applicable.
Bruha, Radan; Dvorak, Karel; Petrtyl, Jaromir
Initiation of alcoholic fatty liver and hepatic inflammation with a specific recall immune response in alcohol-consuming C57Bl/6 mice
Whether immunological responses are involved in initiation and progression of alcoholic liver disease is unclear. We describe a mouse model of alcoholic liver injury characterized by steatosis and hepatic inflammation initiated by a recall immune response. Mice immune to Listeria monocytogenes fed a liquid diet containing ethanol and challenged with viable bacteria developed steatosis within 24 h and, at a later time, elevated serum alanine aminotransferase levels, indicating more liver damage in this group. Listeria antigen also induced steatosis and increased serum alanine aminotransferase levels in immune ethanol-consuming mice. The production of tumour necrosis factor by a recall immune response in this model is a major, but not the only, component in initiation of alcoholic liver disease.
Slukvin, I I; Boor, P J; Jerrells, T R
Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease.
Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients. PMID:24269813
Wu, Weibin; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin
Late acute celiac and hepatic artery thrombosis with portal vein thrombosis resulting in hepatic infarction 12 years post orthotopic liver transplantation.
Hepatic artery thrombosis (HAT) is relatively infrequent, but possibly a devastating complication of orthotopic liver transplantation (OLT). It often requires urgent retransplantation. Two main forms of HAT are recognized as early and late HAT (diagnosis within or after 30 days following LT). Early HAT typically results in graft failure. Late HAT features biliary obstruction, cholangitis, and hepatic abscess formation. We report here the case of a patient of Wilson's disease who presented twelve years post-liver transplant symptoms typical of acute HAT and hepatic infarction. On diagnostic imaging, celiac axis and hepatic artery were thrombosed, resulting in ischemic necrosis of the left hepatic lobe. The resulting sepsis and transient hepatic insufficiency were managed conservatively, and repeat OLT was avoided. The patient remains stable more than one year later. To the best of our knowledge this case report is unique in the literature for the unusually long interval between OLT and late acute HAT, as well as celiac and portal vein occlusion. The acute presentation of sub massive hepatic necrosis is also uncharacteristic of late HAT and more typical of acute HAT. This report describes our experience in managing this and a literature review of the topic. PMID:20009144
Haque, Mazhar; Schumacher, P Andrew; Harris, Alison; Scudamore, Charles H; Steinbrecher, Urs P; Chung, Stephen W; Buczkowski, Andrezj K; Erb, Siegfried R; Yoshida, Eric M
If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...
Effects of Acute Alcohol Consumption in Older and Younger Adults: Perceived Impairment Versus Psychomotor Performance*
Objective: Perceived impairment and psychomotor performance following acute alcohol administration in older (ages 50-74, n = 42; 22 male) and younger (ages 25-35, n = 26; 12 male) adults were investigated in this study. Method: Double-blind, placebo-controlled alcohol administration techniques were designed to produce peak levels of breath alcohol concentration consistent with an episode of social drinking (40 mg/100 ml). Behavioral measures (Trail Making Test, Forms A and B), as well as measures of self-reported perceived intoxication and impairment, were administered on the ascending and descending limbs at common time points after beverage ingestion. Results: Results indicated that psychomotor performance differences did not parallel self-reported levels of perceived impairment. Relative to younger adults, older adults exhibited performance deficits on the ascending limb while simultaneously reporting less perceived impairment. Conversely, on the descending limb, older adults who received alcohol reported more perceived impairment than did those who received placebo, although psychomotor performance between these two groups of older drinkers did not differ. For younger participants, a moderate dose of alcohol facilitated performance on the ascending limb; however, these differences were not reflected on the descending limb. Conclusions: These results reinforce the common knowledge that self-reported measures may not provide an accurate reflection of performance outcomes and, importantly, that older adults may be impaired even under a moderate dose of alcohol, although they may not be aware (i.e., report) of this impairment.
Gilbertson, Rebecca; Ceballos, Natalie A.; Prather, Robert; Nixon, Sara Jo
Stent grafting of acute hepatic artery bleeding following pancreatic head resection.
The purpose of this study was to report the potential of hepatic artery stent grafting in cases of acute hemorrhage of the gastroduodenal artery stump following pancreatic head resection. Five consecutive male patients were treated because of acute, life-threatening massive bleeding. Instead of re-operation, emergency angiography, with the potential of endovascular treatment, was performed. Because of bleeding from the hepatic artery, a stent graft (with the over-the-wire or monorail technique) was implanted to control the hemorrhage by preserving patency of the artery. The outcome was evaluated. In all cases, the hepatic artery stent grafting was successfully performed, and the bleeding was immediately stopped. Clinically, immediately after the procedure, there was an obvious improvement in the general patient condition. There were no immediate procedure-related complications. Completion angiography (n=5) demonstrated control of the hemorrhage and patency of the hepatic artery and the stent graft. Although all patients recovered hemodynamically, three individuals died 2 to 10 days after the procedure. The remaining two patients survived, without the need for re-operation. Transluminal stent graft placement in the hepatic artery is a safe and technically feasible solution to control life-threatening bleeding of the gastroduodenal artery stump. PMID:16932877
Stoupis, Christoforos; Ludwig, Karin; Inderbitzin, Daniel; Do, Dai-Do; Triller, Juergen
Plasma peptidome profiling of acute hepatitis E patients by MALDI-TOF/TOF
Background Hepatitis E is endemic to resource-poor regions, where it manifests as sporadic cases and large waterborne outbreaks. The disease severity ranges from acute self-limited hepatitis with low mortality to fulminant hepatic failure with high mortality. It is believed that the host response plays an important role in determining the progression and outcome of this disease. We profiled the plasma peptidome from hepatitis E patients to discover suitable biomarkers and understand disease pathogenesis. Results The peptidome (< 10 kDa) fraction of plasma was enriched and analyzed by mass spectrometry. A comparative analysis of the peptide pattern of hepatitis E patients versus healthy controls was performed using ClinPro Tools. We generated a peptide profile that could be used for selective identification of hepatitis E cases. We have identified five potential biomarker peaks with m/z values of 9288.6, 7763.6, 4961.5, 1060.572 and 2365.139 that can be used to reliably differentiate between hepatitis E patients and controls with areas under the receiver operating characteristic curve (AUROC) values of 1.00, 0.954, 0.989, 0.960 and 0.829 respectively. A number of proteins involved in innate immunity were identified to be differentially present in the plasma of patients compared to healthy controls. Conclusions Besides the utility of this approach for biomarker discovery, identification of changes in endogenous peptides in hepatitis E patient plasma has increased our understanding of disease pathogenesis. We have identified peptides in plasma that can reliably distinguish hepatitis E patients from healthy controls. Results from this and an earlier proteomics study are discussed.
Acute and residual interactive effects of repeated administrations of oral methamphetamine and alcohol in humans
Although methamphetamine and alcohol are commonly used together in a binge-like pattern, there is a dearth of empirical data investigating the repeated effects of this drug combination. The current study examined acute and residual mood, performance, and physiological effects of methamphetamine alone, alcohol alone, and the combination. Nine adult male volunteers completed this 20-day within-participant, residential laboratory study. During four 5-day blocks of sessions, participants were administered oral methamphetamine (0, 10 mg) combined with alcohol (0, 0.375, 0.75 g/kg) three times (day 2: AM, day 2: PM, and day 3: PM). Breath alcohol concentrations, cardiovascular, subjective, and cognitive/psychomotor performance effects were assessed before drug administration and repeatedly thereafter. Subjective and objective sleep measures were also assessed; residual effects were assessed on days 3¢5 of each block. Following the first drug administration, the methamphetamine¢alcohol combination produced greater elevations of heart rate and ratings of ōgood drug effectö compared to either drug alone. Methamphetamine attenuated alcohol-related performance decrements and feelings of intoxication, whereas alcohol attenuated methamphetamine-related sleep disruptions. By the third administration, many of these effects were significantly diminished, suggesting that participants developed tolerance. Few residual effects were observed. These data show that methamphetamine combined with alcohol produced a profile of effects that was different from the effects of either drug alone. The largely positive effects of the drug combination (i.e., greater euphoria, and fewer performance and sleep disruptions) might explain why these drugs are often used in combination.
Kirkpatrick, Matthew G.; Gunderson, Erik W.; Levin, Frances R.; Foltin, Richard W.; Hart, Carl L.
[A case of acute autoimmune hepatitis associated with autoimmune hemolytic anemia].
A 61-year-old female was admitted to our hospital with severe jaundice and anemia. She was diagnosed with severe acute hepatitis secondary to autoimmune hepatitis (AIH) on the basis of positive anti-nuclear antibody titers, high serum IgG levels, and liver biopsy. Autoimmune hemolytic anemia (AIHA) was diagnosed because of the presence of reticulocytosis, decreased haptoglobin, positive direct Coombs test, and erythroid hyperplasia in the bone marrow. Although AIH occurs in association with various immunological disorders, an association with AIHA is rarely reported. We report a rare case of severe AIH associated with AIHA. PMID:24097153
Hanai, Tatsunori; Naiki, Takafumi; Takamatsu, Manabu; Imai, Kenji; Kitagawa, Junichi; Suetsugu, Atsushi; Takai, Koji; Shiraki, Makoto; Shimizu, Masahito; Hirose, Yoshinobu; Tsurumi, Hisashi; Moriwaki, Hisataka
Hepatic Cryoablation-Induced Acute Lung Injury: Histopathologic Findings
We have previously shown that hepatic cryoablation (cryo), but not partial hepatectomy, induces a systemic inflammatory response, with distant organ injury and overproduction of NF-?B-dependent cytokines. Serum tumor necrosis factor-? (TNF-?) and macrophage inflammatory protein-2 (MIP-2) levels are markedly increased 1 h and beyond after cryo compared with partial hepatectomy where no elevation occurs. NF-?B activation (by electrophoretic mobility shift
Kay Washington; Jacob P. Debelak; Caroline Gobbell; Dora R. Sztipanovits; Yu Shyr; Sandy Olson; William C. Chapman
Performance of anti-HEV assays for diagnosing acute hepatitis E in immunocompromised patients.
Hepatitis E virus is an emerging concern in immunocompromised patients, who may become chronically infected. This prompted us to assess the performance of two anti-HEV IgG and IgM assays for diagnosing acute HEV infections. The specificities of the assays were estimated by testing samples from 2 to 3 year-old French children and blood donors and their sensitivities by testing 40 immunocompromised patients acutely infected. Both anti-HEV IgM assays were highly specific (99.6% and 100%). The sensitivity of the Adaltis was 87.5%, and that of Wantai was 85%. The specificities of anti-HEV IgG Wantai (97.8%) and Adaltis tests (89.5%, p=0.1) were similar but the Wantai test was more sensitive (45%) than the Adaltis test (15%, p<0.001). None of the samples was anti-HEV IgM negative and IgG positive. We conclude that these anti-HEV IgM assays performed well in immunosuppressed subjects with acute hepatitis E and can be used as first line virological tools. Testing for anti-HEV IgG and IgM simultaneously at the acute phase did not improve the diagnostic performance. In contrast, molecular detection of HEV RNA appears essential to exclude an HEV infection in patients who are negative for anti-HEV IgM and to assess the evolution of hepatitis E 3 months thereafter. PMID:24183927
Abravanel, Florence; Chapuy-Regaud, Sabine; Lhomme, Sķbastien; Miedougķ, Marcel; Peron, Jean-Marie; Alric, Laurent; Rostaing, Lionel; Kamar, Nassim; Izopet, Jacques
A randomised controlled trial of extended brief intervention for alcohol dependent patients in an acute hospital setting (ADPAC)
BackgroundĀĀAlcohol dependence affects approximately 3% of the English population, and accounts for significant medical and psychiatric\\u000a morbidity. Only 5.6% of alcohol-dependent individuals ever access specialist treatment and only a small percentage ever seek\\u000a treatment. As people who are alcohol dependent are more likely to have experienced health problems leading to frequent attendance\\u000a at acute hospitals it would seem both sensible
Lynn Owens; Graham Butcher; Ian Gilmore; Ruwanthi Kolamunnage-Dona; James Oyee; Liz Perkins; Tom Walley; Paula Williamson; Ken Wilson; Munir Pirmohamed
Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal
OBJECTIVE: To analyse the evidence for the efficacy and potential harmful effects of benzodiazepines compared with other therapies in the treatment of acute alcohol withdrawal. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1997 that described randomized controlled trials (RCTs) of benzodiazepines in the treatment of acute alcohol withdrawal. Key words included "benzodiazepines" (exploded) and "randomized controlled trial." Bibliographies of relevant articles were reviewed for additional RCTs, and manufacturers of benzodiazepines were asked to submit additional RCT reports not in the literature. STUDY SELECTION: Articles were considered for the meta-analysis if they were RCTs involving patients experiencing acute alcohol withdrawal and comparing a benzodiazepine available in Canada with placebo or an active control drug. Of the original 23 trials identified, 11 met these criteria, representing a total of 1286 patients. DATA EXTRACTION: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. DATA SYNTHESIS: The meta-analysis of benefit (therapeutic success within 2 days) showed that benzodiazepines were superior to placebo (common odds ratio [OR] 3.28, 95% confidence interval [CI] 1.30-8.28). Data on comparisons between benzodiazepines and other drugs, including beta-blockers, carbamazepine and clonidine, could not be pooled, but none of the alternative drugs was found to be clearly more beneficial than the benzodiazepines. The meta-analysis of harm revealed no significant difference between benzodiazepines and alternative drugs in terms of adverse events (common OR 0.67, 95% CI 0.34-1.32) or dropout rates (common OR 0.68, 95% CI 0.47-0.97). INTERPRETATION: Benzodiazepines should remain the drugs of choice for the treatment of acute alcohol withdrawal.
Holbrook, A M; Crowther, R; Lotter, A; Cheng, C; King, D
... C. What is the difference between Hepatitis A, Hepatitis B, and Hepatitis C? Hepatitis A , Hepatitis B , and Hepatitis C are diseases caused by three ... People with Hepatitis A usually improve without treatment. Hepatitis B and Hepatitis C can also begin as acute ...
... C. What is the difference between Hepatitis A, Hepatitis B, and Hepatitis C? Hepatitis A , Hepatitis B , and Hepatitis C are diseases caused by three ... People with Hepatitis A usually improve without treatment. Hepatitis B and Hepatitis C can also begin as acute ...
Liver histology in patients with sporadic acute hepatitis E: a study of 11 patients from South-West France
Hepatitis E virus is a ribonucleic acid (RNA) enterically transmitted virus that causes both epidemics and sporadic cases\\u000a of acute hepatitis E in many countries of Asia and Africa. Domestically acquired (non-travel-associated) hepatitis E has been\\u000a reported recently in many industrialized countries including the USA, Europe, and Japan. There is little information available\\u000a on liver histology in these patients. We
Jean-Marie Peron; Marie Danjoux; Nassim Kamar; Rķda Missoury; HķlĶne Poirson; Jean-Pierre Vinel; Jean-Michel Mansuy; Christophe Bureau; Jacques Izopet; Pierre Brousset; Janick Selves
HEV identified in serum from humans with acute hepatitis and in sewage of animal origin in Spain
Background\\/Aims: Hepatitis E virus (HEV) is an enterically transmitted pathogen that appears sporadically in non-endemic countries. We studied HEV as a causal agent of acute hepatitis cases in the Spanish population, and the role of pigs as an animal reservoir.Methods: The presence of HEV-RNA was analysed by nested polymerase chain reaction in 37 serum samples from patients with acute viral
Sonia Pina; Maria Buti; Montserrat Cotrina; Joan Piella; Rosina Girones
Surgical approach for maintaining nonischemic conditions of the liver in acute hepatic vein obstruction.
To establish a possible surgical approach for preventing warm ischemic injury to the liver followed by hepatic vein occlusion (HVO), the hepatic hemodynamics and energy metabolism were investigated in an acute canine HVO model with and without hepatic arterial blood flow. Arterial blood ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate) and adenylate energy charge potential (ECP = [ATP + 1/2 ADP]/[ATP+ADP+AMP]) of the liver tissue were measured during and after 60 min of HVO. In the group with hepatic arterial blood flow, in which arterial blood was drained by hepatofugal portal flow via the venovenous bypass, total hepatic blood flow, portal vein pressure, ECP, and AKBR were maintained at almost normal level after the termination of HVO, resulting in the survival of all animals for 3 days or longer. By contrast, in the group without hepatic arterial blood flow (warm ischemic group), total hepatic blood flow was maintained at less than 60% of preischemic value, and portal vein pressure gradually increased up to twice the preischemic value. ECP decreased from 0.81 +/- 0.06 to 0.71 +/- 0.07 along with increasing portal venous pressure, and AKBR also decreased from 1.23 +/- 0.12 to 0.63 +/- 0.23, resulting in no survival longer 6 hr. It was concluded that hepatic arterial blood flow during HVO, if drained as hepatofugal portal flow, could maintain nonischemic conditions in the liver, despite vena cava obstruction, by providing an alternate outflow via reversed flow in the portal vein. PMID:7723314
Mitsuyoshi, A; Mashima, S; Terasaki, M; Nakagami, M; Takahashi, K; Nakano, M; Morimoto, T; Yamaoka, Y; Ozawa, K
The use of alcohol is woven into our culture in a most complex fashion. The majority of adults in the United States consume\\u000a alcohol, yet alcohol also causes nearly 75,000 deaths per year and costs our society on the order of 150 billion per year.\\u000a Harm from alcohol can occur in a number of ways. First, if alcohol is consumed
James C. Garbutt
Expression of Cytokine Signaling Genes in Morbidly Obese Patients with Non-Alcoholic Steatohepatitis and Hepatic Fibrosis
BackgroundĀĀWhite adipose tissue (WAT) from visceral adiposity plays an important role in the pathogenesis of non-alcoholic steatohepatitis\\u000a (NASH). Development of NASH and its progression to fibrosis is partially due to cytokines and adipokines produced by WAT.\\u000a The aim of this study was to assess the association of hepatic fibrosis and NASH by evaluating the intrinsic differences in\\u000a the inflammatory cytokine
J. Michael Estep; Ancha Baranova; Noreen Hossain; Hazem Elariny; Kathy Ankrah; Arian Afendy; Vikas Chandhoke; Zobair M. Younossi
CD8+ T-Cell Responses in Acute Hepatitis C Virus Infection
Hepatitis C virus (HCV) infects approximately 170 million people worldwide and is a major cause of life-threatening liver diseases such as liver cirrhosis and hepatocellular carcinoma. Acute HCV infection often progresses to chronic persistent infection, although some patients recover spontaneously. The divergent outcomes of acute HCV infection are known to be determined by differences in virus-specific T-cell responses among patients. Of the two major T-cell subsets, CD8+ T-cells are known to be the key effector cells that control viral infections via cytolytic activity and cytokine secretion. Herein, we review various aspects of HCV-specific CD8+ T-cell responses in acute HCV infection. In particular, we focus on timing of CD8+ T-cell responses, relationship between CD8+ T-cell responses and outcomes of acute HCV infection, receptor expression on CD8+ T-cells, breadth of CD8+ T-cell responses, and viral mutations.
Sung, Pil Soo; Racanelli, Vito; Shin, Eui-Cheol
Alteration of Hepatic Protein Synthesis in Acute Uremia.
National Technical Information Service (NTIS)
Incorporation of L-(U-14C)-leucine into protein was examined in vitro using cell-free preparations of liver from fasting acutely uremic, fasting normal, and non-fasting normal rats. The amount of incorporation was similar in the fasting and nonfasting nor...
G. J. McCormick L. Shear K. G. Barry
Helenalin attenuates alcohol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and suppressing HSC activation.
A compound was isolated from Centipeda minima using bioassay-guided screening. The structure of this compound was elucidated based on its spectral data, and it was identified as helenalin. The hepatoprotective effect of helenalin was evaluated using a liver fibrosis model induced by intragastric administration with alcohol within 24 weeks in rats. The results revealed that helenalin significantly prevented alcohol-induced hepatic injury and fibrogenesis, as evidenced by the decrease in serum aminotransferase, the attenuation of histopathological changes, and the inhibition of the hepatic fibrosis indicators, such as hyaluronic acid, type III precollagen, laminin, hydroxyproline and collagen ? type I. Mechanistically, studies showed that helenalin expedited ethanol metabolism by enhancing the alcohol and aldehyde dehydrogenase activities. Furthermore, helenalin alleviated lipid peroxidation, recruited the antioxidative defense system, inhibited CYP2E1 activity, and reduced the inflammatory mediators, including TGF-?1, TNF-?, IL-6 and IL-1? and myeloperoxidase, via down-regulation of NF-?B. Helenalin significantly decreased collagen deposition by reducing the profibrotic cytokines like transforming growth factor-?, platelet-derived growth factor-? and connective tissue growth factor, and promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9. In addition, helenalin inhibited HSC activation as evidenced by the down-regulation of ?-SMA and TGF-? levels. In conclusion, helenalin had a significant protective effect on chronic ethanol-induced hepatic fibrosis and may be a major bioactive ingredient of C. minima. PMID:24704336
Lin, Xing; Zhang, Shijun; Huang, Renbin; Wei, Ling; Tan, Shimei; Liang, Shuang; Tian, Yuanchun; Wu, Xiaoyan; Lu, Zhongpeng; Huang, Quanfang
Clinical features of acute viral hepatitis B in Korea: a multi-center study
Background/Aims The incidence of Hepatitis B has significantly declined since the introduction of an HBV vaccination program. The aim of this study was to investigate recent clinical features of acute viral hepatitis B (AVH-B) in Korea. Methods A total of 2241 patients with acute viral hepatitis were enrolled and their data were collected from nine medical-centers between January 2006 and December 2009. Results One hundred nineteen (5.3%) of the 2241 were diagnosed as AVH-B. Among 78 patients with AVH-B whose data were analyzed, 50 were male, and the mean age was 38.6 years. In an initial test, mean AST, ALT and total-bilirubin levels were 1296.2 IU/L, 2109.6 IU/L and 9.3 mg/dl, respectively. Positivity frequencies for HBeAg and anti-HBe were 55.1% and 67.9%, respectively, and the mean HBV DNA level was 5.2 log10 copies/ml. The mean length of hospitalization was 11.6 days. During follow-up, AST, ALT and total bilirubin levels were normalized or near-normalized in all patients without serious complications. Sixty-three of 66 (95.4%) patients showed HBsAg loss and 37 (56.1%) patients showed HBsAg seroconversion. Only 3 patients (4.5%) showed persistent hepatitis B viremia. There was no case of death or liver transplantation. Nine patients (11.3%) had received anti-viral agents and their clinical outcomes were not significantly different from those of patients treated without antiviral agents. Conclusions The prevalence of AVH-B among acute hepatitis patients is relatively low in Korea. AVH-B infection can be cured without complications in almost all patients, regardless of antiviral treatment.
Choi, Hye Jin; Choe, Won Hyeok; Seo, Yeon Seok; Kim, Ji Hoon; Byun, Kwan Soo; Kim, Young Seok; Kim, Seung Up; Baik, Soon Koo; Cheong, Jae Youn; Kim, Tae Yeob; Kwon, Oh Sang; Kim, Jeong Han; Lee, Chang Hong; Kwon, So Young
Acute hepatitis A in Italy: incidence, risk factors and preventive measures.
The incidence of, and risk factors for, acute hepatitis A (AHA) were assessed by using data collected from the Italian surveillance system of acute viral hepatitis (SEIEVA). To this end, a case-control study within a population-based surveillance for acute viral hepatitis was performed. AHA incidence has been estimated since 1991; the association with considered risk factors was analysed from 2001 to 2006 employing cases of acute hepatitis B (AHB) as controls. The incidence of AHA declined from 4 / 100 000 in 1991 to 1.4/100 000 in 2006, with a peak during 1996-1998 due to an outbreak in southern Italy. The incidence of AHA was highest among persons aged 15-24 years. The case-fatality rate was 2.9 / 10 000. Contact with individuals with AHA [adjusted OR (OR(adj)) = 3.8, 95% CI 2.7-5.5; population-attributable risk (PAR) = 7.5%], travelling to endemic areas (OR(adj) = 3.1, 95% CI = 2.6-3.8; PAR = 19.5%), ingestion of raw shellfish (OR(adj) = 1.8, 95% CI = 1.6-2.1; PAR = 26.6%), and cohabitation with day care children (OR(adj) = 1.3, 95% CI = 1.01-1.7; PAR = 2.3%) were the main important risk factors. In 2003, an outbreak, with high case-fatality rate occurred among intravenous drug users, in a central Italian town. A weak association was found for male homosexuality when acute hepatitis C cases were employed as controls (OR(adj) = 1.4 CI, 95% CI = 1.1-1.9). Hepatitis A virus infections are currently occurring more frequently in adults, in whom the disease is most severe. In conclusion, looking at the attributable risks, at present most of the AHA infections are due to shellfish consumption, travel to endemic areas and contact with patients with AHA. Vaccination of individuals at increased risk of infection, as well as persons with underling liver disease and those at increased risk of complications, combined with surveillance of shellfish retail outlets are efficient control measures. PMID:18837830
Tosti, M E; Spada, E; Roman", L; Zanetti, A; Mele, A
Acute Thrombocytopenia: An Unusual Complication Occurring After Drug-Eluting Microspheres Transcatheter Hepatic Chemoembolization
Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.
Poggi, Guido, E-mail: firstname.lastname@example.com [Istituto Scientifico di Pavia, Department of Oncology, IRCCS Fondazione S. Maugeri (Italy); Quaretti, Pietro, E-mail: firstname.lastname@example.com [IRCCS Policlinico San Matteo, Department of Interventional Radiology (Italy); Montagna, Benedetta, E-mail: firstname.lastname@example.com; Sottotetti, Federico, E-mail: email@example.com; Tagliaferri, Barbara, E-mail: firstname.lastname@example.com; Pozzi, Emma, E-mail: firstname.lastname@example.com; Amatu, Alessio, E-mail: email@example.com; Pagella, Chiara; Bernardo, Giovanni, E-mail: firstname.lastname@example.com [Istituto Scientifico di Pavia, Department of Oncology, IRCCS Fondazione S. Maugeri (Italy)
Acute Hepatic Encephalopathy Presenting as Cortical Laminar Necrosis: Case Report
We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.
Choi, Jong Mun; Roh, Sook Young
Hepatic expression of CCL2 in alcoholic liver disease is associated with disease severity and neutrophil infiltrates
Serum levels and liver expression of CCL2 are increased in patients with alcoholic hepatitis (AH). In an experimental model of alcoholic liver disease (ALD), CCL2 was implicated in proinflammatory cytokines activation and hepatic lipid metabolism, but its role in human disease is currently unknown. In a large cohort of ALD patients, we analysed plasma levels and liver expression of CCL2 and their association with liver disease severity and histological lesions. We also studied the relationship between ?2518 A > G CCL2 and CCR2 190 A/G polymorphisms and severity of ALD. We show that CCL2 plasma levels are increased in ALD patients compared with healthy subjects. AH patients had significantly higher plasma levels and hepatic expression of CCL2 than patients without AH. Plasma levels and hepatic expression of CCL2 were associated with disease severity. CCL2 liver expression was correlated with neutrophil infiltrate and interleukin (IL)-8 expression, but not with steatosis. Moreover, there were more G-allele carriers of ?2518 A > G CCL2 polymorphism in severe AH patients than in other ALD patients. Our results demonstrate that CCL2 is increased in ALD, particularly in severe forms, and suggest a role for CCL2 in the pathogenesis of ALD via neutrophil recruitment.
Degre, D; Lemmers, A; Gustot, T; Ouziel, R; Trepo, E; Demetter, P; Verset, L; Quertinmont, E; Vercruysse, V; Le Moine, O; Deviere, J; Moreno, C
Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E.
Introduction: Several acute neurological syndromes can be triggered by immune events. Hepatitis E virus (HEV), an emerging infectious disease, can be one of these triggers. Case report: We report the case of a 36-year-old man that presented nausea and a dull abdominal pain for a week and then felt an acute neuralgic pain involving both shoulders that lasted for 8 to 10 hours. Immediately after, the patient presented a severe bilateral muscular weakness of the proximal part of both upper limbs, corresponding to an amyotrophic neuralgia. Two days after the shoulder pain, the patient presented a dysphagia necessitating tube feeding. ĀA blood sample confirmed hepatitis caused by hepatitis E virus (HEV; genotype 3F). Oral feeding resumed progressively after five months. The patient was fully independent for the activities of daily living but was still unable to work after six months. Conclusion: Amyotrophic neuralgia and hepatitis E are both under-diagnosed. It is noteworthy that HEV can trigger amyotrophic neuralgia. Antiviral drugs, oral steroids and intravenous immunoglobulins can be proposed, but the optimal treatment has Ānot yet been determined. PMID:24555112
Moisset, Xavier; Vitello, Nicolas; Bicilli, Elodie; Courtin, Romain; Ferrier, Anna; Taithe, Frederic; Lahaye, Clķment; Hssain, Ali Ait; Garrouste, Cyril; Pierre, Clavelou
Protective effects of taurine against endotoxin-induced acute liver injury after hepatic ischemia reperfusion
Hepatic ischemia reperfusion (HIR) not only results in liver injury, but also leads to endotoxemia, which aggravates HIR-induced\\u000a liver injury and dysfunction, or even causes liver failure. Taurine has been shown to protect organs from ischemia reperfusion\\u000a or endotoxin by its anti-oxidant and anti-inflammatory activities. The aim of this study was to investigate whether taurine\\u000a could attenuate endotoxin-induced acute liver
Feng Zhang; Yahong Mao; Haiquan Qiao; Hongchi Jiang; Haifeng Zhao; Xiaoning Chen; Liquan Tong; Xueying Sun
Serum adenosine deaminase, 5? nucleotidase and malondialdehyde in acute infective hepatitis
Serum adenosine deaminase (ADA), 5? nucleotidase (5?NT) and malondialdehyde (MDA) were estimated in patients with acute infective\\u000a hepatitis (AIH) along with the routine parameters of liver disease. Present study is done to evaluate these special parameters\\u000a in patients with clinical history of AIH and to assess the utility of these parameters as diagnostic\\/ prognostic indices of\\u000a liver function and to
K. Pratibha; Usha Anand; Rajni Agarwal
Acute liver failure secondary to hepatic infiltration: a single centre experience of 18 cases
BackgroundŚAcute liver failure (ALF) secondary to malignant infiltration of the liver is rare and is diagnosed often only after death.AimsŚTo determine diagnostic factors and particular clinical patterns of illness.MethodsŚReview of case notes from all patients with ALF secondary to hepatic infiltration admitted to this unit over an 18 year period (1978¢1995).ResultsŚFrom a total of 4020 admissions, 18 patients were identified
D Rowbotham; J Wendon; R Williams
High Dose Lycopene Supplementation Increases Hepatic Cytochrome P4502E1 Protein and Inflammation in Alcohol-Fed Rats1,2
Recent in vitro evidence suggests that the antioxidant lycopene can prevent alcohol-induced oxidative stress and inflammation. However, knowledge of possible interactions in vivo between escalating doses of lycopene and chronic alcohol ingestion are lacking. In this study, we investigated potential interactions between alcohol ingestion and lycopene supplementation and their effect on hepatic lycopene concentration, cytochrome P4502E1 (CYP2E1) induction, and inflammation.
Sudipta Veeramachaneni; Lynne M. Ausman; Sang Woon Choi; Robert M. Russell; Xiang-Dong Wang
Sustained Hyperresponsiveness of Dendritic Cells Is Associated with Spontaneous Resolution of Acute Hepatitis C
Some studies have reported that dendritic cells (DCs) may be dysfunctional in a subset of patients with chronic hepatitis C virus (HCV) infection. However, the function of DCs during acute HCV infection and their role in determining infectious outcome remain elusive. Here, we examined the phenotype and function of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) during acute HCV infection. Three groups of injection drug users (IDUs) at high risk of HCV infection were studied: an uninfected group, a group with acute HCV infection with spontaneous resolution, and a group with acute infection with chronic evolution. We examined the frequency, maturation status, and cytokine production capacity of DCs in response to the Toll-like receptor 4 (TLR4) and TLR7/8 ligands lipopolysaccharide (LPS) and single-stranded RNA (ssRNA), respectively. Several observations could distinguish HCV-negative IDUs and acute HCV resolvers from patients with acute infection with chronic evolution. First, we observed a decrease in the frequency of mature CD86+, programmed death-1 receptor ligand-positive (PDL1+), and PDL2+ pDCs. This phenotype was associated with the increased sensitivity of pDCs from resolvers and HCV-negative IDUs versus the group with acute infection with chronic evolution to ssRNA stimulation in vitro. Second, LPS-stimulated mDCs from resolvers and HCV-negative IDUs produced higher levels of cytokines than mDCs from the group with acute infection with chronic evolution. Third, mDCs from all patients with acute HCV infection, irrespective of their outcomes, produced higher levels of cytokines during the early acute phase in response to ssRNA than mDCs from healthy controls. However, this hyperresponsiveness was sustained only in spontaneous resolvers. Altogether, our results suggest that the immature pDC phenotype and sustained pDC and mDC hyperresponsiveness are associated with spontaneous resolution of acute HCV infection.
Pelletier, Sandy; Bedard, Nathalie; Said, Elias; Ancuta, Petronela; Bruneau, Julie
Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats
Background Diabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD). Aim of the study The objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats. Methods Diabetes was induced in the animals through intravenous administration of alloxan. The rats were divided into four groups: Diabetic Control (DC) - diabetic rats fed with a control diet and no physical exercise; Diabetic Spirulina (DS) - diabetic rats fed with a diet that included spirulina; Diabetic Spirulina and Exercise (DSE) - diabetic rats fed with a diet that included Spirulina and that exercised; and Diabetic Exercise (DE) - diabetic rats fed with a control diet and that exercised. Results The groups DS, DSE, and DE presented lower plasma concentrations of LDL cholesterol than DC, as well as lower levels of total liver lipids in groups DS, DSE, and DE in comparison to DC. Conclusion Thus, spirulina appears to be effective in reducing total circulating levels of LDL-cholesterol and hepatic lipids, alone or in conjunction with physical exercise in diabetic rats.
Spontaneous Evolution in Bilirubin Levels Predicts Liver-Related Mortality in Patients with Alcoholic Hepatitis
The accurate prognostic stratification of alcoholic hepatitis (AH) is essential for individualized therapeutic decisions. The aim of this study was to develop a new prognostic model to predict liver-related mortality in Asian AH patients. We conducted a hospital-based, retrospective cohort study using 308 patients with AH between 1999 and 2011 (a derivation cohort) and 106 patients with AH between 2005 and 2012 (a validation cohort). The Cox proportional hazards model was constructed to select significant predictors of liver-related death from the derivation cohort. A new prognostic model was internally validated using a bootstrap sampling method. The discriminative performance of this new model was compared with those of other prognostic models using a concordance index in the validation cohort. Bilirubin, prothrombin time, creatinine, potassium at admission, and a spontaneous change in bilirubin levels from day 0 to day 7 (SCBL) were incorporated into a model for AH to grade the severity in an Asian patient cohort (MAGIC). For risk stratification, four risk groups were identified with cutoff scores of 29, 37, and 46 based on the different survival probabilities (P<0.001). In addition, MAGIC showed better discriminative performance for liver-related mortality than any other scoring system in the validation cohort. MAGIC can accurately predict liver-related mortality in Asian patients hospitalized for AH. Therefore, SCBL may help us decide whether patients with AH urgently require corticosteroid treatment.
Lee, Minjong; Kim, Won; Choi, Yunhee; Kim, Sunhee; Kim, Donghee; Yu, Su Jong; Lee, Jeong-Hoon; Kim, Hwi Young; Jung, Yong Jin; Kim, Byeong Gwan; Kim, Yoon Jun; Yoon, Jung-Hwan; Lee, Kook Lae; Lee, Hyo-Suk
Bone Marrow and Nonbone Marrow Toll Like Receptor 4 Regulate Acute Hepatic Injury Induced by Endotoxemia
Background Toll-like receptors (TLRs) are expressed in immune cells and hepatocytes. We examined whether hepatic Toll-like receptor 4 (TLR4) is involved in the acute hepatic injury caused by the administration of lipopolysaccharide (LPS) (septic shock model). Methods Wild type (WT), TLR4-deficient and chimera mice underwent myeloablative bone marrow transplantation to dissociate between TLR4 expression in the liver or in the immune-hematopoietic system. Mice were injected with LPS and sacrificed 4 hours later. Results Compared to TLR4 deficient mice, WT mice challenged with LPS displayed increased serum liver enzymes and hepatic cellular inflammatory infiltrate together with increased serum and hepatic levels of interleukin 1? (IL-1?), tumor necrosis factor ? (TNF?) ,Up-regulation of hepatic mRNA encoding TLR4, I?B and c-jun expressions. TLR4 mutant mice transplanted with WT bone marrow were more protected than WT chimeric mice bearing TLR4 mutant hemopoietic cells from LPS, as seen by IL-1? and TNF? levels. We then used hepatocytes (Huh7) and macrophages from monocytic cell lines to detect TLR mRNA expression. Macrophages expressed a significantly higher level of TLR4 mRNA and TLR2 (more than 3000- and 8000-fold respectively) compared with the hepatocyte cell line. LPS administration induced TLR4 activation in a hepatocyte cell line in a dose dependent manner while TLR2 mRNA hardly changed. Conclusions These results suggest that TLR4 activation of hepatocytes participate in the immediate response to LPS induced hepatic injury. However, in this response, the contribution of TLR4 on bone marrow derived cells is more significant than those of the hepatocytes. The absence of the TLR4 gene plays a pivotal role in reducing hepatic LPS induced injury.
Hochhauser, Edith; Avlas, Orna; Fallach, Reut; Bachmetov, Larissa; Zemel, Romy; Pappo, Orit; Shainberg, Asher; Ben Ari, Ziv
Acute fulminant hepatitis B in a patient with diabetic nephropathy treated successfully with concomitant lamivudine and molecular adsorbents recirculating system.
A 36-year-old man with type 2 diabetes and diabetic nephropathy treated with hemodialysis developed hepatitis B virus (HBV)-induced acute fulminant hepatic failure (FHF). Despite supportive treatment, the condition rapidly progressed as manifested by severe jaundice, coagulopathy and hepatic coma. He was placed on the waiting list for liver transplantation and was treated with lamivudine and extracoporeal liver support with the molecular adsorbent recirculating system (MARS). After three 8-h sessions of MARS treatment in 1 week, he had remarkable improvement in clinical symptoms and serum biochemistry. On the 14th hospital day, surface antigen seroconversion was noted with undetectable hepatitis B virus surface antigen (HBs Ag) and low titre of anti-HBs antibody, indicating a complete recovery from acute fulminant hepatitis B. MARS treatment has been reported to benefit patients with liver failure from different causes including acute exacerbation of chronic hepatitis B, poisoning, post transplantation and Wilson's disease. The present case suggests its potential benefit when combined with lamivudine in treating uremic patients with acute fulminant hepatitis B. PMID:16269182
Tsai, Shih-Hung; Chang, Hao-Ming; Hsieh, Chung-Bao; Chao, You-Chen; Hsieh, Tsai-Yuan
Serum aminotransferase activity as a predictor for estimation of total clearance of hepatically metabolized drugs in rats with acute hepatic failure.
The levels of serum aminotransferase activity, including aspartate aminotransferase (AST), in rats with acute hepatic failure at 24 h after an oral administration of CCl4 (0.01-0.5 ml/kg) were about 15-50 times higher (up to nearly 5000 IU/l) than those of vehicle control rats (about 85 IU/l). The values of total clearance (CL(tot)) of cyclosporin A, doxorubicin, tacrolimus and zonisamide in the CCl4-treated rats were decreased to about 1/2-1/3 of those in control rats. There were good correlations between AST activity and hepatic intrinsic clearance (CL(int)) (r=0.733-0.949) for the above drugs, as well as for chlorzoxazone, caffeine, lidocaine and tolbutamide after the intravenous administration of each drug in rats with acute hepatic failure. However, the slope of the linear regression equation, i.e., the ratio of decrease of CL(int) against increase of AST activity, differed markedly among these drugs. We found that there is a good correlation (r=0.953) between the values of the slope and the CL(int) of normal rats for these drugs, except for caffeine. In summary, the linear regression equation enables us to predict the decrease of CL(tot) in rats with acute hepatic failure to be predicted from the increase in serum AST activity. This approach may be useful as a guide for the dose modification of drugs for patients with acute hepatic failure. PMID:16394527
Yokogawa, Koichi; Ido, Akane; Kurihara, Takeshi; Mano, Yasunari; Nomura, Masaaki; Ishizaki, Junko; Miyamoto, Ken-Ichi
Protective Effect of Essential Oil from Zingiber Officinale (Zingiberaceae) on Acute Alcohol-Induced Liver Injury in Mice
Oxidative stress and lipid abnormalities after ethanol consumption are suggested to play a key role in the development of alcoholic liver injury. We investigated the induction of oxidative damage in association with triglyceride abnormalities in hepatic concentrations mice challenged with ethanol administration. Also the protective effect of ginger essential oil (GEO) extracted with supercritical carbon dioxide against ethanol-induced liver injury
Ping Liu; Jingming Li; Liyan Ma; Shuyan Li; Yuanying Ni
... if they've been vaccinated against it. Continue Hepatitis B Hepatitis B is a more serious infection. It may lead ... of which cause severe illness and even death. Hepatitis B virus (HBV) is transmitted from person to person ...
... into the food and water supply. Back Continue Hepatitis B and Hepatitis C Although hep A is a ... does Ś through direct contact with infected body fluids. Hepatitis B and C are even more easily passed in ...
Micro-RNA-122 levels in acute liver failure and chronic hepatitis C.
MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV-HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P?0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P?0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed. J. Med. Virol. 86:1507-1514, 2014. ® 2014 Wiley Periodicals, Inc. PMID:24895202
Dubin, Perry H; Yuan, Hejun; Devine, Robert K; Hynan, Linda S; Jain, Mamta K; Lee, William M
TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure. Subtle inter-patient genetic variation and environmental factors combine to determine variation in disease progression. A common non-synonymous polymorphism in TM6SF2 (rs58542926 c.449 C>T, p.Glu167Lys) was recently associated with increased hepatic triglyceride content, but whether this variant promotes clinically relevant hepatic fibrosis is unknown. Here we confirm that TM6SF2 minor allele carriage is associated with NAFLD and is causally related to a previously reported chromosome 19 GWAS signal that was ascribed to the gene NCAN. Furthermore, using two histologically characterized cohorts encompassing steatosis, steatohepatitis, fibrosis and cirrhosis (combined n=1,074), we demonstrate a new association, independent of potential confounding factors (age, BMI, type 2 diabetes mellitus and PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis. These findings establish new and important clinical relevance to TM6SF2 in NAFLD. PMID:24978903
Liu, Yang-Lin; Reeves, Helen L; Burt, Alastair D; Tiniakos, Dina; McPherson, Stuart; Leathart, Julian B S; Allison, Michael E D; Alexander, Graeme J; Piguet, Anne-Christine; Anty, Rodolphe; Donaldson, Peter; Aithal, Guruprasad P; Francque, Sven; Van Gaal, Luc; Clement, Karine; Ratziu, Vlad; Dufour, Jean-Francois; Day, Christopher P; Daly, Ann K; Anstee, Quentin M
Spontaneous resolution of pancreatic masses (pseudocysts?)--Development and disappearance after acute alcoholic pancreatitis.
To determine the incidence and the natural history of retroperitoneal masses complicating acute pancreatitis, 104 cases of acute alcoholic pancreatitis were evaluated prospectively for mass formation. Abdominal masses detected by physical examination and serial x-ray films of the upper portion of the gastrointestinal tract were localized to the retroperitoneum by additional contrast studies, including abdominal angiography. Nonoperative management was urged only for patients with an asymptomatic mass. An abdominal mass developed in 19 patients (18%). In eight of these, it disappeared rapidly, but in 11 (11%), it persisted, and was considered to be a pancreatic pseudocyst. Eight of the 11 patients were treated nonoperatively, and the mass resolved without complication three weeks to three months after diagnosis. In three patients, a pseudocyst was confirmed at laparotomy. Exploration was justified by an unstable clinical course in only one instance. A routine surgical approach to an asymptomatic retroperitoneal mass developing after acute alcoholic pancreatitis may not be necessaary in patients who are improving clinically because the mass may resolve without complication. PMID:1138670
Czaja, A J; Fisher, M; Marin, G A
Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy
The spread of hepatitis B virus (HBV) infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B, from 10/100000 inhabitants in 1984 to 0.85/100000 in 2012, and by the reduced prevalence of hepatitis B surface antigen (HBsAg)-positive cases among chronic hepatitis patients with different etiologies, from 60% in 1975 to about 10% in 2001. The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3% in the 1980s to 1% in 2010. Linked to HBV by its characteristics of defective virus, the hepatitis delta virus (HDV) has shown a similar epidemiological impact on the Italian population over time. The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from 24% in 1990 to 8.5% in 2006. Before the beneficial effects of HBV mass vaccination introduced in 1991, the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations, the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size. A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds.
Sagnelli, Evangelista; Sagnelli, Caterina; Pisaturo, Mariantonietta; Macera, Margherita; Coppola, Nicola
Gigantic hepatic amebic abscess presenting as acute abdomen: a case report
Introduction Amebiasis is a parasitic disease caused by Entamoeba histolytica. It most commonly results in asymptomatic colonization of the gastrointestinal tract, but some patients develop intestinal invasive or extra-intestinal diseases. Liver abscess is the most common extra-intestinal manifestation. The large number of clinical presentations of amebic liver abscess makes the diagnosis very challenging in non-endemic countries. Late diagnosis of the amebic abscess may lead to perforation and amebic peritonitis, resulting in high mortality rates. Case presentation This report describes a 37-year-old white man, suffering from hepatitis B, with a gigantic amebic liver abscess presenting as an acute abdomen due to its rupture. Rapid deterioration of the patient's condition and acute abdomen led to an emergency operation. A large volume of free fluid together with debris was found at the moment of entry into the peritoneal cavity because of a rupture of the hepatic abscess at the position of the segment VIII. Surgical drainage of the hepatic abscess was performed; two wide drains were placed in the remaining hepatic cavities and one on the right hemithorax. The patient was hospitalized in the ICU for 14 days and for another 14 days in our department. The diagnosis of amebic abscess was made by the pathologists who identified E. histolytica in the debris. Conclusion Acute abdomen due to a ruptured amebic liver abscess is extremely rare in western countries where the parasite is not endemic. Prompt diagnosis and treatment are fundamental to preserving the patient's life since the mortality rates remain extremely high when untreated, even nowadays.
Papavramidis, TS; Sapalidis, K; Pappas, D; Karagianopoulou, G; Trikoupi, A; Souleimanis, Ch; Papavramidis, ST
Brief report: no evidence for parvovirus B19 or hepatitis E virus as a cause of acute liver failure.
Viral hepatitis A and B are known to cause acute liver failure. While nearly 20% of acute liver failure cases are of indeterminate etiology, screening for other viruses has not been uniformly performed. We looked for evidence for parvovirus B19 and hepatitis E virus in sera from U.S. acute liver failure patients. For B19, 78 patients' sera, including 34 with indeterminate etiology, were evaluated by DNA dot-blot hybridization, reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay for immunoglobin G and M antibodies; none showed evidence for infection. PMID:16964546
Lee, W M; Brown, K E; Young, N S; Dawson, G J; Schlauder, G G; Gutierrez, R A; Fontana, R; Rossaro, L; Davern, T; Lalani, E
Acute myocardial infarction induced by concurrent use of adderall and alcohol in an adolescent.
Adderall (amphetamine, dextroamphetamine mixed salts), a widely prescribed stimulant for the treatment of attention-deficit/hyperactivity disorder in children and adolescents, is considered safe with due precautions. Nonmedical use of Adderall is prevalent and rising in high school and college students. Use of prescribed Adderall without intention to overdose as a cause of myocardial infarction is extremely rare, and to our knowledge, only 3 cases have been reported in the pediatric literature. We report a case of acute myocardial infarction in an adolescent without cardiovascular risk factors who took the total prescribed daily dose of Adderall one time while consuming alcohol. The sporadic use of Adderall with alcohol creates a potentially dangerous situation with serious cardiovascular adverse effects. We should have a high degree of suspicion for children and adolescents on stimulant therapy who present with chest pain and an abnormal electrocardiogram in the pediatric emergency department, and there is a need to evaluate them for myocardial ischemia and infarction. PMID:23283274
Sharma, Jayendra; de Castro, Carlyle; Chatterjee, Partha; Pinto, Rohit
Suicide is a major public health problem in the United States as well as around the world. The significant role that alcohol plays in suicidality is well known and accepted in the scientific community. The use of alcohol does not necessarily lead to suicide, but through its action and effects, alcohol is an important proximal risk factor for suicidal behavior. There is very little data showing how and why alcohol exerts such tremendous influence and ōlubricates the gearsö to propel the act of committing suicide. This article will elucidate the complex relationship between alcohol and suicide and how alcohol use can lead to suicide. The article also describes how alcohol affects brain neurophysiology in regards to suicidal behavior.
Nathani, Milankumar; Jabeen, Shahgufta; Yazdani, Ijlal; Mouton, Charles D.; Bailey, Rahn K.; Mahr, Mona; Pate, Rebecca J.; Riley, Wayne J.
Necro-inflammatory response of pancreatic acinar cells in the pathogenesis of acute alcoholic pancreatitis
The role of pancreatic acinar cells in initiating necro-inflammatory responses during the early onset of alcoholic acute pancreatitis (AP) has not been fully evaluated. We investigated the ability of acinar cells to generate pro- and anti-inflammatory mediators, including inflammasome-associated IL-18/caspase-1, and evaluated acinar cell necrosis in an animal model of AP and human samples. Rats were fed either an ethanol-containing or control diet for 14 weeks and killed 3 or 24?h after a single lipopolysaccharide (LPS) injection. Inflammasome components and necro-inflammation were evaluated in acinar cells by immunofluorescence (IF), histology, and biochemical approaches. Alcohol exposure enhanced acinar cell-specific production of TNF?, IL-6, MCP-1 and IL-10, as early as 3?h after LPS, whereas IL-18 and caspase-1 were evident 24?h later. Alcohol enhanced LPS-induced TNF? expression, whereas blockade of LPS signaling diminished TNF? production in vitro, indicating that the response of pancreatic acinar cells to LPS is similar to that of immune cells. Similar results were observed from acinar cells in samples from patients with acute/recurrent pancreatitis. Although morphologic examination of sub-clinical AP showed no visible signs of necrosis, early loss of pancreatic HMGB1 and increased systemic levels of HMGB1 and LDH were observed, indicating that this strong systemic inflammatory response is associated with little pancreatic necrosis. These results suggest that TLR-4-positive acinar cells respond to LPS by activating the inflammasome and producing pro- and anti-inflammatory mediators during the development of mild, sub-clinical AP, and that these effects are exacerbated by alcohol injury.
Gu, H; Werner, J; Bergmann, F; Whitcomb, D C; Buchler, M W; Fortunato, F
Clinical Presentation and Course of Acute Hepatitis C Infection in HIV-Infected Patients
Hepatitis C virus (HCV) has become a significant source of morbidity and mortality in HIV-infected patients. However, little is known about the clinical presentation and course of acute HCV infection in this population. This study reports the outcomes of acute HCV infection in 9 HIV-infected men. Sex with men was the only reported risk factor for HCV infection in 6 of the subjects. Clinical presentation of acute HCV ranged from incidentally discovered elevated transaminases to severe liver dysfunction requiring hospitalization. At the time of HCV diagnosis, 8 of 9 patients had CD4+ counts >250 cells/mm3, and 6 had HIV viral loads of ?5000 copies/mL. Eight patients were receiving antiretroviral therapy. Outcome of these acute HCV infections varied. Five patients experienced virologic clearance, 2 in whom virus cleared spontaneously and 3 who were treated with pegylated interferon and ribavirin. Four patients developed chronic infection, one of whom had a relapse during HCV treatment and 3 of whom were untreated. All 4 patients to whom HCV therapy was administered experienced significant anemia or neutropenia, necessitating dose reduction or support with growth factors. Prompt recognition of acute HCV infection may minimize antiretroviral treatment interruption and will allow early treatment, which may improve virologic clearance. Unexplained transaminase elevations in HIV-infected patients, including men who have sex with men, should trigger an evaluation for acute HCV infection.
Luetkemeyer, Annie; Hare, Bradley; Stansell, John; Tien, Phyllis C.; Charlesbois, Edwin; Lum, Paula; Havlir, Diane; Peters, Marion
Molecular adsorbent recirculating system treatment for acute hepatic failure in patients with hepatitis B undergoing chemotherapy for non-Hodgkin's lymphoma.
Hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface (HBsAg) antigen-positive patients treated with chemotherapy. Because the hepatitis is related to HBV virological reactivation, application of effective antiviral therapy, such as Lamivudine, has been attempted. Despite the use of these antiviral agents at the time of clinical hepatitis, some HBsAg-positive patients still develop hepatic failure and die. We used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock, Germany) to treat 5 HBsAg-positive lymphoma patients with acute hepatic failure due to chemotherapy despite lamivudine treatment. Before and after each treatment we monitored the parameters of neurological status (EEG, cerebral CT and Glasgow coma score), hemodynamic parameters, acid-base equilibrium and blood gases as well as hepatic and renal function. The inclusion criteria were these of the King's College Hospital. Statistical analysis by Student t method showed significant results (P < .01). Three of 5 patients are alive without signs of reactivation of viral or hematological diseases at 1 year follow-up. The 2 patients died because MARS treatment was started too late, with Glascow coma score grade IV, hemodynamic instability, and mechanical ventilator assistance. Despite the limited number of cases, we believe that MARS can be applied to patients with a high tolerance and yield good results, but the treatment has to start at the first signs of hepatic failure. PMID:16182743
Novelli, G; Rossi, M; Ferretti, G; Nudo, F; Bussotti, A; Mennini, G; Novelli, L; Ferretti, S; Antonellis, F; Martelli, S; Berloco, P B
Metabolomic analysis of arginine metabolism in acute hepatic injury in rats.
To clarify the relationship between arginine metabolism and hepatic injury, metabolomic analysis was performed in rats treated with 3 representative hepatotoxicants, monocrotaline (MCT), concanavalin A (ConA), and ?-naphthyl isothiocyanate (ANIT); or a myotoxicant, tetramethyl-p-phenylenediamine (TMPD). A single dose of MCT, ConA, or ANIT dose-dependently induced hepatocellular necrosis accompanied by decreased blood arginine and increased blood alanine aminotransferase (ALT) and arginase. A close correlation was detected between arginine and ALT (r = -0.746, -0.795, -0.787 for MCT, ConA, ANIT, respectively) or between arginine and arginase (r = -0.605, -0.808, -0.672 for MCT, ConA, ANIT, respectively) in all three hepatic injury models. In contrast, neither hepatocellular necrosis nor alterations in arginine were found in the skeletal muscle injury model, although ALT was slightly increased. An in vitro assay revealed that blood samples obtained from ConA-treated rats transformed external arginine to ornithine, and the reaction was totally inhibited by an arginase inhibitor. These results suggest that blood arginase plays a crucial role in arginine metabolism associated with hepatic injury. In metabolomic analysis, nearly 450 endogenous metabolites were identified in blood obtained from all the models. Among the 13 metabolites involved in arginine metabolism, decreased arginine and increased ornithine occurred in common in the hepatic injury models, whereas citrulline and other metabolites were not altered. These results indicate that arginine metabolism, especially the arginine-to-ornithine pathway, is altered in association with acute hepatic injury. Furthermore, blood arginine and ornithine are possibly specific biomarkers for hepatic injury. PMID:24418708
Saitoh, Wataru; Yamauchi, Shusuke; Watanabe, Kyoko; Takasaki, Wataru; Mori, Kazuhiko
Endovascular Treatment of Acute Arterial Hemorrhage in Trauma Patients Using Ethylene Vinyl Alcohol Copolymer (Onyx)
PurposeĀĀThis study was designed to determine the feasibility and efficacy of endovascular embolization with liquid embolic agent ethylene\\u000a vinyl alcohol copolymer (Onyx) in patients with acute traumatic arterial bleeding.\\u000a \\u000a \\u000a \\u000a \\u000a MethodsĀĀThis is a retrospective review of 13 patients (9 men and 4 women; mean age 45Āyears) with severe trauma who underwent embolotherapy\\u000a using Onyx from November 2003 to February 2009. Bleeding
R. M³ller-Wille; P. Heiss; T. Herold; E. M. Jung; A. G. Schreyer; O. W. Hamer; J. Rennert; P. Hoffstetter; C. Stroszczynski; N. Zorger
Chlorella vulgaris extract ameliorates carbon tetrachloride-induced acute hepatic injury in mice.
The possible protective effects of Chlorella vulgaris extract (CVE) on carbon tetrachloride (CCl(4))-induced acute hepatic injury in mice and the mechanism underlying these effects was investigated. CCl(4) administration caused a marked increase in the levels of serum aminotransferases, lipid peroxidation and cytochrome P450-2E1 (CYP450) expression. Also, decreased glutathione (GSH) content and activities of cellular antioxidant defense enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and glutathione-S-transferase (GST) were found after CCl(4) exposure. All of these phenotypes were markedly reversed by preadministration of the mice with CVE. In addition, CVE exhibited antioxidant effects on FeCl(2)-ascorbate induced lipid peroxidation in mouse liver homogenates, and on superoxide radical scavenging activity. Taken together, these results suggest that CVE produced a protective action on CCl(4)-induced acute hepatic injury in mice, presumably through blocking CYP-mediated CCl(4) bioactivation, inducing the GSH levels, antioxidant enzyme activities and free radical scavenging effect. Therefore, CVE may be an effective hepatoprotective agent and viable candidate for treating hepatic disorders and other oxidative stress-related diseases. PMID:21741806
Li, Li; Li, Wei; Kim, Yong-Ho; Lee, Yong Woo
Effect of sinapic acid against carbon tetrachloride-induced acute hepatic injury in rats.
Acute hepatic inflammation is regarded as a hallmark of early stage fibrosis, which can progress to extensive fibrosis and cirrhosis. Sinapic acid is a phenylpropanoid compound that is abundant in cereals, nuts, oil seeds, and berries and has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the anti-inflammatory effect of sinapic acid in carbon tetrachloride (CCl4)-induced acute hepatic injury in rats. Sinapic acid was administered orally (10 or 20 mg/kg) to rats at 30 min and 16 h before CCl4 intoxication. Sinapic acid treatment of rats reduced CCl4-induced abnormalities in liver histology, serum alanine transaminase and aspartate transaminase activities, and liver malondialdehyde levels. In addition, sinapic acid treatment significantly attenuated the CCl4-induced production of inflammatory mediators, including tumor necrosis factor-alpha and interleukin-1? mRNA levels, and increased the expression of nuclear factor-kappa B (NF-?B p65). Sinapic acid exhibited strong free radical scavenging activity in vitro. Thus, sinapic acid protected the rat liver from CCl4-induced inflammation, most likely by acting as a free radical scavenger and modulator of NF-?B p65 activation and proinflammatory cytokine expression. Sinapic acid may thus have potential as a therapeutic agent for suppressing hepatic inflammation. PMID:23494565
Shin, Dong-Su; Kim, Kung Wook; Chung, Hae Young; Yoon, Sik; Moon, Jeon-Ok
Protective Effect of N-Acetylserotonin against Acute Hepatic Ischemia-Reperfusion Injury in Mice
The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD) was evaluated by enzyme-linked immunosorbent assay (ELISA). The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury.
Yu, Shuna; Zheng, Jie; Jiang, Zhengchen; Shi, Caixing; Li, Jin; Du, Xiaodong; Wang, Hailiang; Jiang, Jiying; Wang, Xin
Involvement of AMPK in Alcohol Dehydrogenase Accentuated Myocardial Dysfunction Following Acute Ethanol Challenge in Mice
Objectives Binge alcohol drinking often triggers myocardial contractile dysfunction although the underlying mechanism is not fully clear. This study was designed to examine the impact of cardiac-specific overexpression of alcohol dehydrogenase (ADH) on ethanol-induced change in cardiac contractile function, intracellular Ca2+ homeostasis, insulin and AMP-dependent kinase (AMPK) signaling. Methods ADH transgenic and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Oral glucose tolerance test, cardiac AMP/ATP levels, cardiac contractile function, intracellular Ca2+ handling and AMPK signaling (including ACC and LKB1) were examined. Results Ethanol exposure led to glucose intolerance, elevated plasma insulin, compromised cardiac contractile and intracellular Ca2+ properties, downregulated protein phosphatase PP2A subunit and PPAR-?, as well as phosphorylation of AMPK, ACC and LKB1, all of which except plasma insulin were overtly accentuated by ADH transgene. Interestingly, myocardium from ethanol-treated FVB mice displayed enhanced expression of PP2C? and PGC-1?, decreased insulin receptor expression as well as unchanged expression of Glut4, the response of which was unaffected by ADH. Cardiac AMP-to-ATP ratio was significantly enhanced by ethanol exposure with a more pronounced increase in ADH mice. In addition, the AMPK inhibitor compound C (10 ĄM) abrogated acute ethanol exposure-elicited cardiomyocyte mechanical dysfunction. Conclusions In summary, these data suggest that the ADH transgene exacerbated acute ethanol toxicity-induced myocardial contractile dysfunction, intracellular Ca2+ mishandling and glucose intolerance, indicating a role of ADH in acute ethanol toxicity-induced cardiac dysfunction possibly related to altered cellular fuel AMPK signaling cascade.
Guo, Rui; Scott, Glenda I.; Ren, Jun
Phenprocoumon-induced liver disease ranges from mild acute hepatitis to (sub-) acute liver failure
Background\\/AimsExcept for bleeding complications, other serious adverse reactions of coumarin anticoagulants such as hepatotoxicity or skin necrosis are comparatively rare. Nonetheless, a small number of coumarin-induced (sub-) acute liver failures has been published.
Carl C. Schimanski; J³rgen Burg; Markus M÷hler; Thomas H÷hler; Stephan Kanzler; Gerd Otto; Peter R. Galle; Ansgar W. Lohse
Amanitin toxicosis in two cats with acute hepatic and renal failure.
Amanitin is a toxic cyclopeptide present in several species of poisonous mushrooms. Amanitin toxicosis was diagnosed in 2 cats from separate premises. Both cats initially had lethargy and vomiting, and they rapidly developed depression and neurological signs over 24-48 hours. Marked elevation of alanine aminotransferase was the primary finding, with subsequent serum chemistry values compatible with hepatic and renal failure. Histopathological findings consisted of submassive to massive acute hepatic necrosis, renal proximal tubular epithelial necrosis, and foci of necrosis and inflammation in the gastrointestinal tract. Amanitin exposure was confirmed postmortem by detection of ?-amanitin in the kidney by liquid chromatography-mass spectrometry. A similar clinical course and pathological changes are reported in human and canine amanitin intoxication; however, gastrointestinal lesions are not typically described. PMID:22184185
Tokarz, D; Poppenga, R; Kaae, J; Filigenzi, M; Lowenstine, L J; Pesavento, P
Mycoplasma pneumonia-associated acute hepatitis in an adult patient without lung infection.
Mycoplasma pneumonia is a major cause of respiratory infections in school-aged children. Most M. pneumonia infections in adults involve the respiratory tract. Extrapulmonary manifestations of M. pneumonia infection may be found in the skin, cardiovascular, neurologic and hematologic systems. Concomitant liver disease is rare in adults. Here, we report an unusual case of a patient who presented with fever and abdominal pain, but without pulmonary manifestations. The laboratory work-up demonstrated a hepatocellular pattern of acute hepatitis caused by M. pneumonia infection. Symptoms subsided and laboratory parameters improved with antibiotics treatment. Thus, this case can help raise clinicians' awareness of the possibility of M. pneumonia infection, with or without lung involvement, as a part of the evaluation of undetermined hepatitis. PMID:19372077
Lee, Shou-Wu; Yang, Sheng-Shun; Chang, Chi-Sen; Yeh, Hong-Jeh; Chow, Wai-Keung
Acute Hepatic Failure as a Leading Manifestation in Exertional Heat Stroke
Background. Acute hepatic failure (AHF) is uncommon as a leading symptom in patients with exertional heat stroke (EHS). Which stage to perform the liver transplantation for severe hepatic failure in EHS is still obscure at clinical setting. The conservative management has been reported to be successful in treating heat-stroke-associated AHF even in the presence of accepted criteria for emergency liver transplantation. Case Presentation. Here, we reported a 35-year-old male who presented with very high transaminases, hyperbilirubinemia, significant prolongation of the prothrombin time, and coma. No other causes for AHF could be identified but physical exhaustion and hyperthermia. Although the current patient fulfilled London criteria for emergency liver transplantation, he spontaneously recovered under conservative treatment including intravenous fluids, cooling, diuretics as mannitol, and hepatocyte growth-promoting factors. Conclusions. Meticulous supportive management could be justified in some selected cases of AHF due to EHS.
Jin, Qi; Chen, Erzhen; Jiang, Jie; Lu, Yiming
Treatment of acute hepatitis C in breast cancer patient: a case report.
Oncologists worldwide are often dealing with hepatitis C virus positive breast cancer patients, questioning adequate chemotherapy protocol, reduction of doses, delays, or even interruptions of treatment. We present a case of a woman in stage IIIB breast cancer, who after the completion of neoadjuvant treatment developed significant increase in liver enzymes and was diagnosed positive for HCV. She was treated with interferon and after the resolving of acute liver disease continued concomitant treatment with interferon, ribavirin, docetaxel, and trastuzumab. Grade 4 neutropenia and grade 3 hepatotoxicity occurred after the third cycle of chemo and 5 months of antiviral therapy. Interferon and chemotherapy were postponed for 1 week. There are no sufficient data in order to recommend the concomitant antiviral and antineoplastic therapy. Hepatitis C virus and antiviral therapy may increase the toxicities of antineoplastic treatment. However, when lifesaving oncologic treatment is necessary, concomitant antiviral therapy can be administered with more intensive follow up. PMID:24621156
Matovina-Brko, Gorana; Ruzic, Maja; Fabri, Milotka; Popovic, Lazar; Kolarov-Bjelobrk, Ivana; Trifunovic, Jasna; Petkovic, Danijela
Acute alcohol effects on attentional bias are mediated by subcortical areas associated with arousal and salience attribution.
Acute alcohol ingestion increases attentional bias to alcohol-related stimuli; however, the underlying cognitive and brain mechanisms remain unknown. We combined functional magnetic resonance imaging (fMRI) with performance of a dual task that probed attentional distraction by alcohol-related stimuli during 'conflict' processing: the Concurrent Flanker/Alcohol-Attentional bias task (CFAAT). In this task, an Eriksen Flanker task is superimposed on task-unrelated background pictures with alcohol-associated or neutral content. Participants respond to the direction of a central 'target' arrow and ignore adjacent congruent (low cognitive load) or incongruent (high cognitive load) 'flanking' arrows. Using a between-subject design, 40 healthy moderate-to-heavy social drinkers received either no alcohol (placebo), 0.4?g/kg (low dose), or 0.8?g/kg (high dose) of alcohol, and underwent fMRI while performing the CFAAT. The low alcohol dose, relative to placebo, increased response latencies on trials with alcohol-associated backgrounds and, under low cognitive load, increased the activity evoked by these pictures within a medial hypothalamic region. Under high cognitive load, the low alcohol dose, relative to placebo, elicited greater activity within a more lateral hypothalamic region, and reduced activity within frontal motor areas. The high alcohol dose, relative to placebo, did not reliably affect response latencies or neural responses to background images, but reduced overall accuracy under high cognitive load. This effect correlated with changes in reactivity within medial and dorsal prefrontal cortices. These data suggest that alcohol at a low dose primes attentional bias to alcohol-associated stimuli, an effect mediated by activation of subcortical hypothalamic areas implicated in arousal and salience attribution. PMID:23361162
Nikolaou, Kyriaki; Field, Matt; Critchley, Hugo; Duka, Theodora
Use of Nucleoside (Tide) Analogues in Patients with Hepatitis B-Related Acute Liver Failure
Background & Aims The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF. Methods The US Acute Liver Failure Study Group, a 23-site registry prospectively enrolled 1,413 patients with ALF with different etiologies between 1998 and 2008. Of those, 105 patients were identified as HBV-ALF patients, of whom we excluded those without data on NA use or with co-infection with hepatitis C, leaving 85 patients, 43 of whom had received NA treatment. HBV-DNA on admission was quantified by real time polymerase chain reaction. Results The treated and untreated groups were similar in most respects but differed significantly in regard to higher aminotransferase and bilirubin levels and hepatic coma grades, all being observed in the untreated group. Median duration of NA treatment was 6 (range: 1-21) days. Overall survival in the NA treated and untreated groups were 61% and 64% respectively (p=0.72). Rates of transplant-free survival were 21% and 36% in the treated and untreated groups respectively, p=0.42. Multivariate analysis revealed that not using a NA [odds ratio (OR) 4.4, 95% CI 1.1-18.1, p=0.041], hepatic coma grade I or II [OR 14.4, 95% CI 3.3-62.8, p<0.001], prolonged prothrombin time (PT) [OR 0.59, 95% CI 0.39-0.89, p=0.012] were predictors of improved transplant-free survival. Conclusions Patients who are admitted with established HBV-ALF do not appear to benefit from viral suppression using nucleoside(tide) analogues presumably because of rapid disease evolution and short treatment duration. Despite the lack of benefit, NAs should still be given to transplantation candidates since viral suppression prevents recurrence after grafting.
Dao, Doan Y; Seremba, Emmanuel; Ajmera, Veeral; Sanders, Corron; Hynan, Linda S.; Lee, William M.
Nine scoring models for short-term mortality in alcoholic hepatitis: cross-validation in a biopsy-proven cohort
Background Several prognostic models have emerged in alcoholic hepatitis (AH), but lack of external validation precludes their universal use. Aim To validate the Maddrey Discriminant Function (DF); Glasgow Alcoholic Hepatitis Score (GAHS); Mayo End-stage Liver Disease (MELD); Age, Bilirubin, INR, Creatinine (ABIC); MELD-Na, UK End-stage Liver Disease (UKELD), and three scores of corticosteroid response at 1Āweek: an Early Change in Bilirubin Levels (ECBL), a 25% fall in bilirubin, and the Lille score. Methods Seventy-one consecutive patients with biopsy-proven AH, admitted between November 2007-September 2011, were evaluated. The clinical and biochemical parameters were analysed to assess prognostic models with respect to 30- and 90-day mortality. Results There were no significant differences in the areas under the receiver operating characteristics curve (AUROCs) relative to 30-day/90-day mortality: MELD 0.79/0.84, DF 0.71/0.74, GAHS 0.75/0.78, ABIC 0.71/0.78, MELD-Na 0.68/0.76, UKELD 0.56/0.68. One-week rescoring yielded a trend towards improved predictive accuracies (30-day/90-day AUROCs: 0.69¢0.84/0.77¢0.86). In patients with admission DF ?32 (nĀ=Ā31), response to corticosteroids according to ECBL, 25% fall in bilirubin and the Lille model yielded AUROCs of 0.73/0.73, 0.78/0.72 and 0.81/0.82 for a 30-day/90-day outcome respectively. All models showed excellent negative predictive values (NPVs; range: 86¢100%), while the positive ones were low (range: 17¢50%). Conclusions MELD, DF, GAHS, ABIC and scores of corticosteroid response proved to be valid in an independent cohort of biopsy-proven alcoholic hepatitis. MELD modifications incorporating sodium did not confer any prognostic advantage over classical MELD. Based on excellent NPVs, the models are best to identify patients at low risk of death.
Papastergiou, V; Tsochatzis, E A; Pieri, G; Thalassinos, E; Dhar, A; Bruno, S; Karatapanis, S; Luong, T V; O'Beirne, J; Patch, D; Thorburn, D; Burroughs, A K
Preservation of hepatocyte nuclear factor 4? contributes to the beneficial effect of dietary medium chain triglyceride on alcohol-induced hepatic lipid dyshomeostasis in rats
Background Alcohol consumption is a major cause of fatty liver, and dietary saturated fats have been shown to protect against alcoholic fatty liver. This study investigated the mechanisms of how dietary saturated fat may modulate alcohol-induced hepatic lipid dyshomeostasis. Methods Rats were pair-fed with 3 isocaloric liquid diets, control, alcohol, and medium chain triglyceride (MCT)/alcohol, respectively, for 8 weeks. The control and alcohol diets were based on the Lieber-DeCarli liquid diet formula with 30% total calories derived from corn oil (rich in unsaturated long chain fatty acids). The corn oil was replaced by MCT, which consists of exclusive saturated fatty acids, in the MCT/alcohol diet. HepG2 cell culture was conducted to test the effects of unsaturated fatty acids on HNF4? and the role of HNF4? in regulating hepatocyte lipid homeostasis. Results Alcohol feeding caused significant lipid accumulation, which was attenuated by dietary MCT. The major effect of alcohol on hepatic gene expression is the up-regulation of CYP4A1, CD36 and GPAT3, and down-regulation of apolipoprotein B (ApoB). Dietary MCT further up-regulated CYP4A1 gene, normalized ApoB gene and up-regulated MTTP and SCD1 genes. The protein level of hepatocyte nuclear factor-4? (HNF4?), a master transcription factor of the liver, was reduced by alcohol feeding, which was normalized by dietary MCT. Fatty acid profiling demonstrated that alcohol feeding dramatically increased hepatic unsaturated long chain fatty acyl species, particularly linoleic acid and oleic acid, which was attenuated by dietary MCT. Dietary MCT attenuated alcohol-reduced serum triglyceride level and modulated the fatty acid composition of the serum triglycerides. Cell culture study demonstrated polyunsaturated linoleic acid rather than monounsaturated oleic acid inactivated HNF4? in HepG2 cells. Knockdown HNF4? caused lipid accumulation in HepG2 cells due to dysregulation of very low density lipoprotein secretion. Conclusions Results suggest that dietary MCT prevents alcohol-induced hepatic lipid accumulation, at least partially, through reducing hepatic polyunsaturated long chain fatty acids and preserving HNF4?.
Li, Qiong; Zhong, Wei; Qiu, Yunping; Kang, Xinqin; Sun, Xiuhua; Tan, Xiaobing; Zhao, Yantao; Sun, Xinguo; Jia, Wei; Zhou, Zhanxiang
Predictors of the outcomes of acute-on-chronic hepatitis B liver failure
AIM: To identify the risk factors in predicting the outcome of acute-on-chronic hepatitis B liver failure patients. METHODS: We retrospectively divided 113 patients with acute-on-chronic liver failure-hepatitis B virus (ACLF-HBV) and without concurrent hepatitis C or D virus infection and hepatocellular carcinoma into two groups according to their outcomes after anti-HBV therapy. Their demographic, clinical, and biochemical data on the day of diagnosis and after the first week of treatment were analyzed using the Mann-Whitney U test, FisherÆs exact test, and a multiple logistic regression analysis. RESULTS: The study included 113 patients (87 men and 26 women) with a mean age of 49.84 years. Fifty-two patients survived, and 61 patients died. Liver failure (85.2%), sepsis (34.4%), and multiple organ failure (39.3%) were the main causes of death. Multivariate analyses showed that Acute Physiology and Chronic Health Evaluation (APACHE)?II scores ? 12 [odds ratio (OR) = 7.160, 95% CI: 2.834-18.092, P < 0.001] and positive blood culture (OR = 13.520, 95% CI: 2.740-66.721, P = 0.001) on the day of diagnosis and model for end-stage liver disease (MELD) scores ? 28 (OR = 8.182, 95% CI: 1.884-35.527, P = 0.005) after the first week of treatment were independent predictors of mortality. CONCLUSION: APACHE II scores on the day of diagnosis and MELD scores after the first week of anti-HBV therapy are feasible predictors of outcome in ACLF-HBV patients.
Fan, Hsiu-Lung; Yang, Po-Sheng; Chen, Hui-Wei; Chen, Teng-Wei; Chan, De-Chuan; Chu, Chi-Hong; Yu, Jyh-Cherng; Kuo, Shih-Ming; Hsieh, Chung-Bao
Effects of acute alcohol consumption on alcohol-related cognitive biases in light and heavy drinkers are task-dependent.
We investigated (1) the effects of alcohol on cognitive biases for alcohol-related cues, (2) the effects of drinking status on alcohol-related cognitive biases and (3) the similarity of any effects of alcohol across two measures of alcohol cognitive bias. Healthy, heavy and light social alcohol users (n = 72) were examined in a single-blind placebo-controlled design. Participants received 0.00 g/kg, 0.13 g/kg or 0.40 g/kg of alcohol in a between-subjects design and then completed both a modified Stroop task and a visual probe task. Modified Stroop data indicated a main effect of cue type, which was qualified by drinking status, with heavier drinkers slower to respond to alcohol-related cues. Visual probe data, in contrast, indicated a significant interaction effect between validity (valid: alcohol-related, invalid: neutral) and drink condition. Participants receiving a moderate dose of alcohol (0.40 g/kg) were faster to respond to alcohol-related stimuli compared with participants receiving a low dose of alcohol or placebo. These data indicate that the cognitive processes assayed by the visual probe and Stroop tasks may not be mediated by a common underlying mechanism. PMID:21708838
Adams, Sally; Ataya, Alia F; Attwood, Angela S; Munaf", Marcus R
Are heat stroke and physical exhaustion underestimated causes of acute hepatic failure?
While cardiopulmonary symptoms are common in patients undergoing classical or, due to physical exercise, exertional heat stroke, the failure of other organs is a rarely described phenomenon. Here we present two cases of acute hepatic failure, one due to classic heat shock, while the other occurred while the patient was doing a marathon-type running. Both cases presented with very high transaminases and significantly elevated international normalized ratio (INR). No other causes for liver failure could be identified but physical exhaustion and hyperthermia.
Weigand, Kilian; Riediger, Carina; Stremmel, Wolfgang; Flechtenmacher, Christa; Encke, Jens
Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation
The circadian clock orchestrates temporal patterns of physiology and behavior relative to the environmental light:dark cycle by generating and organizing transcriptional and biochemical rhythms in cells and tissues throughout the body. Circadian clock genes have been shown to regulate the physiology and function of the gastrointestinal tract. Disruption of the intestinal epithelial barrier enables the translocation of proinflammatory bacterial products, such as endotoxin, across the intestinal wall and into systemic circulation; a process that has been linked to pathologic inflammatory states associated with metabolic, hepatic, cardiovascular and neurodegenerative diseases ¢ many of which are commonly reported in shift workers. Here we report, for the first time, that circadian disorganization, using independent genetic and environmental strategies, increases permeability of the intestinal epithelial barrier (i.e., gut leakiness) in mice. Utilizing chronic alcohol consumption as a well-established model of induced intestinal hyperpermeability, we also found that both genetic and environmental circadian disruption promote alcohol-induced gut leakiness, endotoxemia and steatohepatitis, possibly through a mechanism involving the tight junction protein occludin. Circadian organization thus appears critical for the maintenance of intestinal barrier integrity, especially in the context of injurious agents, such as alcohol. Circadian disruption may therefore represent a previously unrecognized risk factor underlying the susceptibility to or development of alcoholic liver disease, as well as other conditions associated with intestinal hyperpermeability and an endotoxin-triggered inflammatory state.
Forsyth, Christopher B.; Shaikh, Maliha; Cavanaugh, Kate; Tang, Yueming; Vitaterna, Martha Hotz; Song, Shiwen
Acute alcohol ingestion reduces fatty acid extraction of the heart, liver, and small intestine.
Ethanol may have profound effects on both the distribution of perfusion and substrate utilization by the liver and heart due to its vasodilating properties and the generation of high levels of circulating acetate and lactate. Since fatty acids are highly extracted by the heart and liver under normal circumstances, changes in the relationship of perfusion/fatty acid uptake may be a sensitive indicator of both altered perfusion and changes in metabolic substrate availability. To test this hypothesis, studies were performed in rats fed 3.1, 6.2, and 9.3 g/kg doses of ethanol. Fatty acid uptake was estimated with a 3-methyl substituted reagent with a chain length equivalent to 17 carbons. The methyl group in the three position prevented beta oxidation and prolonged the residence of fatty acids in the tissue. Eighteen hours after acute alcohol administration, fatty acid uptake was reduced in the heart and the small intestine; in the liver uptake was increased or unchanged. Acute ethanol administration also resulted in increased perfusion, as indicated by enhanced uptake of 201thallium by the heart, liver, and small intestine. The fatty acid extraction of the heart, liver, and small intestine, defined as the concentration of fatty acid divided by the concentration of 201thallium, was markedly decreased by alcohol ingestion. These alcohol effects were dose-dependent and temporally related. The data suggest that ethanol ingestion could potentially alter heart function during exercise or following a prolonged fast, when the heart relies primarily upon fatty acids extracted from the circulation to generated adenosine triphosphate (ATP). PMID:2264611
Carter, E A; Barli-Kovach, M; Elmaleh, D; Livni, E; Strauss, H W
Plasma interferon-gamma-inducible protein-10 (IP-10) levels during acute hepatitis C virus infection.
Systemic levels of interferon-gamma-inducible protein-10 (IP-10) are predictive of treatment-induced clearance in chronic hepatitis C virus (HCV). In the present study, factors associated with plasma IP-10 levels at the time of acute HCV detection and the association between IP-10 levels and spontaneous clearance were assessed in three cohorts of acute HCV infection. Among 299 individuals, 245 (181 male, 47 human immunodeficiency virus-positive [HIV+]) were HCV RNA+ at acute HCV detection. In adjusted analysis, factors independently associated with IP-10 levels ?150 pg/mL (median level) included HCV RNA levels >6 log IU/mL, HIV coinfection and non-Aboriginal ethnicity. Among 245 HCV RNA+ at acute HCV detection, 214 were untreated (n = 137) or had persistent infection (infection duration ?26 weeks) at treatment initiation (n = 77). Spontaneous clearance occurred in 14% (29 of 214). Individuals without spontaneous clearance had significantly higher mean plasma IP-10 levels at the time of acute HCV detection than those with clearance (248 ▒ 32 versus 142 ▒ 22 pg/mL, P = 0.008). The proportion of individuals with spontaneous clearance was 0% (0 of 22, P = 0.048) and 16% (27 of 165) and in those with and without plasma IP-10 levels ?380 pg/mL. In adjusted analyses, favorable IL28B genotype was associated with spontaneous clearance, while higher HCV RNA level was independently associated with lower odds of spontaneous clearance. Conclusion: High IP-10 levels at acute HCV detection were associated with failure to spontaneously clear HCV. Patients with acute HCV and high baseline IP-10 levels, particularly >380 pg/mL, should be considered for early therapeutic intervention, and those with low levels should defer therapy for potential spontaneous clearance. (HEPATOLOGY 2013;). PMID:23325615
Grebely, Jason; Feld, Jordan J; Applegate, Tanya; Matthews, Gail V; Hellard, Margaret; Sherker, Alana; Petoumenos, Kathy; Zang, Geng; Shaw, Ineke; Yeung, Barbara; George, Jacob; Teutsch, Suzy; Kaldor, John M; Cherepanov, Vera; Bruneau, Julie; Shoukry, Naglaa H; Lloyd, Andrew R; Dore, Gregory J
Acute Increase in Hepatic Arterial Flow During TIPS Identified by Intravascular Flow Measurements
The purpose of this study was to investigate alterations of hepatic arterial flow during transjugular intrahepatic portosystemic stent shunt (TIPS) applying intravascular Doppler sonography. This prospective monocenter study included 25 patients with liver cirrhosis (alcohol induced [n = 19], chronic hepatitis associated [n = 3], primary biliary cirrhosis associated [n = 1], and cryptogenic [n = 2]) successfully treated with TIPS. All patients underwent intravascular hepatic arterial flow measurements during TIPS using an endoluminal flow sensor. The average arterial peak velocity (APV) and the maximum arterial peak velocity (MPV) were registered. Twenty-two patients (88%) showed increased APV, one patient (4%) showed unaffected APV, and two patients (8%) showed decreased APV after TIPS. The average portosystemic pressure gradient decreased significantly, from 22.0 {+-} 5.1 mmHg before TIPS to 11.0 {+-} 4.1 mmHg after TIPS (-50.0%; p < 0.0001). The average APV increased significantly, from 41.9 {+-} 17.8 cm/s before TIPS to 60.7 {+-} 19.0 cm/s after TIPS (+44.9%; p < 0.0001). The average MPV increased significantly, from 90.8 {+-} 31.7 cm/s before TIPS to 112.6 {+-} 34.9 cm/s after TIPS (+24.0%; p = 0.0002). These changes in perfusion set in within seconds after TIPS tract formation in all the patients with increased APV. We conclude that TIPS-induced portosystemic decompression leads to a significant increase in hepatic arterial flow. The changes occurred within seconds, suggesting a reflex-like mechanism.
Radeleff, Boris, E-mail: firstname.lastname@example.com; Sommer, Christof-Matthias; Heye, Tobias; Lopez-Benitez, Ruben [University of Heidelberg Medical Center, Department of Diagnostic Radiology (Germany); Sauer, Peter [University of Heidelberg Medical Center, Department of Internal Medicine IV, Gastroenterology, Hepatology, Infectious Diseases, and Intoxications (Germany); Schmidt, Jan [University of Heidelberg Medical Center, General, Visceral, and Accident Surgery (Germany); Kauczor, Haus-Ulrich; Richter, Goetz Martin [University of Heidelberg Medical Center, Department of Diagnostic Radiology (Germany)
Hepatic unsaturated fatty acids in patients with non-alcoholic fatty liver disease assessed by 3.0 T MR spectroscopy
Rationale and objectiveNon-alcoholic fatty liver disease (NAFLD) is related to the metabolic syndrome and obesity. Proton magnetic resonance spectroscopy (1H MRS) is a non-invasive technique to assess hepatic triglyceride content (HTGC) and allows assessment of unsaturated fatty acids (UFA). There is increasing evidence that hepatic UFA are associated with the development of NAFLD. Therefore the objective of this study was
J. R. van Werven; T. C. M. A. Schreuder; A. J. Nederveen; C. Lavini; P. L. M. Jansen; J. Stoker
Chromosome abnormalities in chronic active hepatitis
An investigation on human peripheral blood lymphocyte chromosomes in chronic active hepatitis was carried out. A higher percentage of chromatid and chromosome lesions was recorded in all patients studied as compared with control groupsŚnormal individuals, healthy subjects who had suffered from acute viral hepatitis, patients with alcoholic liver disease, and patients with mechanical jaundice due to cancer. The possible origin of these abnormalities is discussed.
Stefanescu, D. T.; Moanga, M.; Teodorescu, M.; Brucher, J.
Serum lipase and amylase ratio in acute alcoholic and nonalcoholic pancreatitis by using Dupont ACA discrete clinical analyzer
This work involves a retrospective analysis of serum amylase, lipase, and lipase\\/amylase ratio in alcoholic and nonalcoholic patients diagnosed with acute pancreatitis. The purpose of this study was to test the reliability of the Dupont ACA method with respect to the lipase\\/amylase ratio as a discriminator, for the etiology of pancreatitis. Thirty-six consecutive patients with the diagnosis of acute pancreatitis
Ehsan Ansari; David A. Talenti; Joseph A. Scopelliti; Jawad M. Saadat; Bradley D. Zehr
Assessing candidacy for acute hepatitis C treatment among active young injection drug users: a case-series report.
Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All five acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. Establishing treatment candidacy for young IDU in the acute phase involves various health domains. An acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care. PMID:21497111
Asher, Alice; Lum, Paula J; Page, Kimberly
Dibromosulphophthalein: its pharmacokinetics and binding to hepatic cytosol proteins in rats with acute renal failure.
1. The pharmacokinetics, biliary excretion and binding of dibromosulphophthalein (DBSP) to plasma proteins and hepatic cytosol proteins have been studied in male rats with glycerol-induced acute renal failure (ARF). 2. The rate constants for hepatic uptake, efflux from liver to plasma and excretion into bile were all significantly decreased in rats with ARF. Furthermore, the plasma clearance of DBSP was also reduced. 3. The initial (0-10 min) and maximum biliary excretion rates of DBSP were both diminished in animals with ARF. The maximum excretion rate occurred between 5-10 min in control rats and 10-15 min in rats with ARF. However, there was no statistically significant change in the percentage dose recovered from bile after 30 min. 4. The plasma-protein binding of DBSP was decreased in rats with ARF and this change was due to a significant reduction in the association constant for the primary binding sites. 5. The binding of DBSP to ligandin (Y protein) was reduced by about 38% in rats with ARF but no change was noted in binding to Z protein. Reduced binding to ligandin was accompanied by decreased total liver glutathione S-transferase (GST) activity and a 36% reduction in the GST activity of ligandin. 6. The results support the contention that altered hepatic handling of cholephilic dyes in rats with ARF may be due to reduced binding to ligandin.
Silberstein, D. J.; Bowmer, C. J.; Yates, M. S.
Inhibitory effect of angiotensin II receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis
AIM: To investigate the efficacy of angiotensin II receptor antagonist on hepatic stellate cells (HSCs) activation in the patients with non-alcoholic steatohepatitis (NASH). METHODS: Seven patients with NASH were prescribed losartan, a selective angiotensin II type 1 receptor antagonist (50 mg/d) for 48 wk. Liver biopsies were performed both at the entry and end of the study in all patients. Quiescent and activated HSCs were identified by double immunostaining using anti-p75 and ?-smooth muscle actin antibodies, and the number of each phenotype was counted. Similarly, the liver specimens obtained from the eight patients with non-alcoholic fatty liver (NAFL) were also examined as controls. RESULTS: In NASH hepatic tissues, activated HSCs were dominantly distributed as compared with those in NAFL. The 48-wk losartan treatment induced a remarkable decrease in activated HSCs and a mild increase in quiescent phenotypes. CONCLUSION: Our data suggest the crucial involvement of HSCs in anti-fibrotic effect of angiotensin II receptor antagonist on patients with NASH.
Yokohama, Shiro; Tokusashi, Yoshihiko; Nakamura, Kimihide; Tamaki, Yosui; Okamoto, Satoshi; Okada, Mituyoshi; Aso, Kazunobu; Hasegawa, Takenao; Aoshima, Masaru; Miyokawa, Naoyuki; Haneda, Masakazu; Yoneda, Masashi
Zeaxanthin Dipalmitate Therapeutically Improves Hepatic Functions in an Alcoholic Fatty Liver Disease Model through Modulating MAPK Pathway.
In the current study, the therapeutic effects of zeaxanthin dipalmitate (ZD) on a rat alcoholic fatty liver disease (AFLD) model were evaluated. After-treatment with ZD from the 5th week to the 10th week in a 10-week ethanol intragastric administration in rats significantly alleviated the typical AFLD symptoms, including reduction in rat body weight, accumulation of hepatic fat droplets, occurrence of oxidative stress, inflammation, chemoattractive responses and hepatic apoptosis in the liver. The reduction of liver function abnormalities by ZD was partly through lower expression level of cytochrome P450 2E1 (CYP2E1), diminished activity of nuclear factor kappa B (NF-?B) through the restoration of its inhibitor kappa B alpha (I?B?), and the modulation of MAPK pathways including p38 MAPK, JNK and ERK. ZD treatment alone did not pose obvious adverse effect on the healthy rat. In the cellular AFLD model, we also confirmed the inhibition of p38 MAPK and ERK abolished the beneficial effects of ZD. These results provide a scientific rationale for the use of zeaxanthin and its derivatives as new complementary agents for the prevention and treatment of alcoholic liver diseases. PMID:24740309
Xiao, Jia; Wang, Jiteng; Xing, Feiyue; Han, Tao; Jiao, Rui; Liong, Emily C; Fung, Man-Lung; So, Kwok-Fai; Tipoe, George L
Zeaxanthin Dipalmitate Therapeutically Improves Hepatic Functions in an Alcoholic Fatty Liver Disease Model through Modulating MAPK Pathway
In the current study, the therapeutic effects of zeaxanthin dipalmitate (ZD) on a rat alcoholic fatty liver disease (AFLD) model were evaluated. After-treatment with ZD from the 5th week to the 10th week in a 10-week ethanol intragastric administration in rats significantly alleviated the typical AFLD symptoms, including reduction in rat body weight, accumulation of hepatic fat droplets, occurrence of oxidative stress, inflammation, chemoattractive responses and hepatic apoptosis in the liver. The reduction of liver function abnormalities by ZD was partly through lower expression level of cytochrome P450 2E1 (CYP2E1), diminished activity of nuclear factor kappa B (NF-?B) through the restoration of its inhibitor kappa B alpha (I?B?), and the modulation of MAPK pathways including p38 MAPK, JNK and ERK. ZD treatment alone did not pose obvious adverse effect on the healthy rat. In the cellular AFLD model, we also confirmed the inhibition of p38 MAPK and ERK abolished the beneficial effects of ZD. These results provide a scientific rationale for the use of zeaxanthin and its derivatives as new complementary agents for the prevention and treatment of alcoholic liver diseases.
Xing, Feiyue; Han, Tao; Jiao, Rui; Liong, Emily C.; Fung, Man-Lung; So, Kwok-Fai; Tipoe, George L.
What factors determine the severity of hepatitis A-related acute liver failure?
The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were sub-genotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P?0.01). At another centre, a mother and her son presented with HAV and liver failure within 1?month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare sub-genotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes. PMID:21143345
Ajmera, V; Xia, G; Vaughan, G; Forbi, J C; Ganova-Raeva, L M; Khudyakov, Y; Opio, C K; Taylor, R; Restrepo, R; Munoz, S; Fontana, R J; Lee, W M
... fun. You might see people drinking and watching sports together or having a big party. But alcohol is actually a depressant . That means it's a drug that slows down or depresses the brain . Like ...
Self-reported physiological and psychological side-effects of an acute alcohol and energy drink dose.
Objective: There have been repeated calls from health professionals and policy-makers to clarify the side-effects of the increasingly popular consumption trend of alcohol mixed with energy drinks (AmED). There is a dearth of research assessing the differential effects of AmED relative to alcohol by comparing self-reported psychological and physiological outcomes whilst under the influence of these substances. The aim of the present study was to examine the acute effects of a moderate alcohol and energy drink (ED) dose on self-reported psychological and physiological outcomes. Method: Using a single-blind, placebo-controlled, crossover design, 28 adults completed four sessions where they were administered: (i) 0.50g/kg alcohol, (ii) 3.57mL/kg ED, (iii) AmED, and (iv) placebo. Participants independently completed the Profile of Mood States and a Somatic Symptom Scale at baseline and at 30 and 125min after beverage administration. Results: Breath alcohol concentration peaked at .068% and .067% in the alcohol and AmED conditions, respectively. There were no interactive alcohol and ED effects on self-reported psychological outcomes. Treatment effects for physiological outcomes generally only related to alcohol or ED administration, with the exception of a moderate magnitude decrease in heart palpitation ratings following alcohol relative to AmED. Decreased muscular tension ratings were evident when the two constituents were consumed separately relative to placebo. Conclusions: The results provide evidence of few subjective changes in physiological and psychological state after consuming AmED relative to alcohol. The majority of treatment-based changes arose from the independent effects of alcohol or ED, rather than being modified by their interaction. However, research extending into higher dosage domains is required to increase outcome generalisability for consumers in the night-time economy. PMID:24462484
Peacock, Amy; Bruno, Raimondo; Martin, Frances H; Carr, Andrea
Clinical, histologic and serologic evaluation of patients with acute non-A-E hepatitis in north-eastern Brazil: is it an infectious disease?
Non-A-E hepatitis and acute cryptogenic hepatitis are the names given to the disease of patients with clinical hepatitis, but in whom serologic evidence of A-E hepatitis has not been found. Over a period of 8 years, we evaluated in Brazil 32 patients who fulfilled the criteria for this diagnosis in order to determine patterns of the clinical illness, laboratory parameters,
Raymundo Paranß; Zilton Andrade; Luiz A. R. de Freitas; Rogķrio Santos-Jesus; Mitermayer Reis; Helma Cotrim; Simone Cunha; Christian Trepo
Acute liver failure caused by concurrent autoimmune hepatitis and hepatitis B in a 16-year old girl
A 16 year-old girl was admitted to hospital because of fatigue and somnolence, nausea, epistaxis and jaundice. Physical examination revealed jaundice, an enlarged liver and tenderness of upper right abdomen. Laboratory tests revealed an increased level of acute liver failure, bilirubin, bile acids, GGTP and a decreased prothrombin ratio, with elevated gamma-globulin and IgG levels, and the presence of anti-mitochondrial M2 antibodies and HBV infection markers. The patient was diagnosed with liver failure resulting from chronic hepatitis B with an autoimmune component. The treatment consisted of steroids, azathioprine, vitamin K, low-protein diet and lactulose enemas. After undergoing a molecular test (HBV DNA 3.23 ū 105 IU/mL and mutations I 204 and I 80), the treatment was modified by adding entecavir. After one month the patient was discharged in good clinical condition, with the recommendation of continued entecavir, prednisone and azathioprine. In subsequent months, no clinical deterioration or abnormal biochemical liver function test results were found, despite the discontinuation of immunosuppressive therapy after 10 mo. The patient continues entecavir therapy.
Pawlowska, Malgorzata; Halota, Waldemar
Biochemical Evaluation of Patients of Alcoholic Liver Disease and Non-alcoholic Liver Disease.
Alcoholic liver disease (ALD) is due to excessive alcohol intake for long duration. Distinguishing ALD from non-ALD (non-alcoholic steatohepatitis, hepatitis of viral origin) is difficult as patient may deny alcohol abuse. Clinical examination, histology and serology may not differentiate these conditions. Accurate diagnosis is important as management of ALD differs from non-ALD patients. The aim of our study was (1) To evaluate the patients of ALD and non-ALD by biochemical parameters compared to controls, (2) To assess whether these parameters can differentiate ALD from non-ALD. Study was carried out on 50 patients of ALD in group I and 35 patients of NASH (non-alcoholic steatohepatitis) and acute viral hepatitis each in group II. Age matched healthy controls nĀ=Ā50. Selection criteria-history of alcohol intake (amount and duration), clinical examination, sonography of abdomen, serum alanine transaminase (ALT) and bilirubin levels. Blood samples were analyzed for bilirubin, aspartate transaminase (AST), ALT, alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) by kinetic method. Statistical analysis was done by Student unpaired 't' test. Patients of ALD have raised AST/ALT ratio (De Ritis ratio) (>2), ALP and GGT compared to controls (PĀ<Ā0.01).There is significant difference in AST/ALT ratio, serum GGT and ALP in ALD group compared to that in NASH and acute viral hepatitis (PĀ<Ā0.05). This study suggests that De Ritis ratioĀ>2 in ALD patients may be due to alcohol induced hepatic mitochondrial injury and pyridoxine deficiency. High GGT and ALP values may indicate enzyme induction by alcohol and mild cholestasis. Thus ALD patients have severe hepatic damage. De Ritis ratioĀ<1 and normal to mild elevation in GGT level in NASH and acute viral hepatitis suggest mild hepatic injury of non-alcoholic origin. Our study concludes that ALD patients can be differentiated from NASH and acute viral hepatitis with certainty by measuring serum AST/ALT ratio, GGT and ALP. These biochemical parameters may help clinicians to support the diagnosis of ALD and non-ALD. PMID:24478554
Torkadi, Prasad P; Apte, I C; Bhute, A K
Acute intermittent porphyria causes hepatic mitochondrial energetic failure in a mouse model.
Acute intermittent porphyria (AIP), an inherited hepatic disorder, is due to a defect of hydroxymethylbilane synthase (HMBS), an enzyme involved in heme biosynthesis. AIP is characterized by recurrent, life-threatening attacks at least partly due to the increased hepatic production of 5-aminolaevulinic acid (ALA). Both the mitochondrial enzyme, ALA synthase (ALAS) 1, involved in the first step of heme biosynthesis, which is closely linked to mitochondrial bioenergetic pathways, and the promise of an ALAS1 siRNA hepatic therapy in humans, led us to investigate hepatic energetic metabolism in Hmbs KO mice treated with phenobarbital. The mitochondrial respiratory chain (RC) and the tricarboxylic acid (TCA) cycle were explored in the Hmbs(-/-) mouse model. RC and TCA cycle were significantly affected in comparison to controls in mice treated with phenobarbital with decreased activities of RC complexes I (-52%, (**)p<0.01), II (-50%, (**)p<0.01) and III (-55%, (*)p<0.05), and decreased activity of ?-ketoglutarate dehydrogenase (-64%, (*)p<0.05), citrate synthase (-48%, (**)p<0.01) and succinate dehydrogenase (-53%, (*)p<0.05). Complex II-driven succinate respiration was also significantly affected. Most of these metabolic alterations were at least partially restored after the phenobarbital arrest and heme arginate administration. These results suggest a cataplerosis of the TCA cycle induced by phenobarbital, caused by the massive withdrawal of succinyl-CoA by ALAS induction, such that the TCA cycle is unable to supply the reduced cofactors to the RC. This profound and reversible impact of AIP on mitochondrial energetic metabolism offers new insights into the beneficial effect of heme, glucose and ALAS1 siRNA treatments by limiting the cataplerosis of TCA cycle. PMID:24727425
Homedan, Chadi; Laafi, Jihane; Schmitt, Caroline; Gueguen, Na'g; Lefebvre, Thibaud; Karim, Zoubida; Desquiret-Dumas, Valķrie; Wetterwald, Cķline; Deybach, Jean-Charles; Gouya, Laurent; Puy, Hervķ; Reynier, Pascal; MalthiĶry, Yves
Management of severe acute to fulminant hepatitis B: to treat or not to treat or when to treat?
Despite a decline in cases of acute hepatitis B and the low hepatitis B virus (HBV) chronicity rates in adults, still some patients progress to HBV-related fulminant liver failure. In this review, we discuss treatment options that may prevent the progression of severe acute hepatitis B to fulminant liver failure and death. In severe acute HBV with prolonged prothrombin time and increased bilirubin, interferon failed to be effective while antiviral treatment, particularly with lamivudine, appears to improve survival (mean survival almost 80%). Outcome without antiviral therapy has remained considerably poor, whereas there is no convincing evidence of amelioration of HBV-targeted immunity. Of note, most patients who died or required transplantation despite lamivudine therapy, were started on lamivudine at advanced stages compared with those survived. This suggests that prompt and timely antiviral therapy is crucial. Owing to the abovementioned results the design of randomized placebo-control trials in the setting of severe acute hepatitis B seems unethical. On the contrary, the design of multicentre double-blind randomized trials to compare the efficacy between lamivudine and entecavir or even tenofovir in acute severe HBV cases is ideally needed, but these studies appear to be very difficult to perform considering that these cases are not frequent and therefore, it is almost impossible to have two arms adequately numerous and homogenous for statistical evaluation. Thus, in the absence of solid evidence based data, the hepatologists could treat their patients with severe acute hepatitis B with lamivudine or the most potent antivirals entecavir or tenofovir. PMID:22099371
Tillmann, Hans L; Zachou, Kalliopi; Dalekos, George N
Phosphorus-31 nuclear magnetic resonance spectroscopic study of the canine pancreas: applications to acute alcoholic pancreatitis
The first nuclear magnetic resonance spectroscopic study of the canine pancreas is described. Both in-vivo, ex-vivo protocols and NMR observables are discussed. The stability of the ex-vivo preparation based on the NMR observables is established for at least four hours. The spectra obtained from the in-vivo and ex-vivo preparations exhibited similar metabolite ratios, further validating the model. Metabolite levels were unchanged by a 50% increase in perfusion rate. Only trace amounts of phosphocreatine were observed either in the intact gland or in extracts. Acute alcoholic pancreatitis was mimicked by free fatty acid infusion. Injury resulted in hyperamylasemia, edema (weight gain), increased hematocrit and perfusion pressure, and depressed levels of high energy phosphates.
Janes, N.; Clemens, J.A.; Glickson, J.D.; Cameron, J.L.
Rac1 modulates acute and subacute genotoxin-induced hepatic stress responses, fibrosis and liver aging.
To investigate the importance of the Ras-homologous GTPase Rac1 for the hepatic response to genotoxic insults and liver aging, rac1 was deleted in liver of mice by Mx1-Cre-based recombination. Knockout of rac1 caused complex changes in basal as well as doxorubicin and ionizing radiation-induced mRNA expression of various genotoxic stress response-related genes, including hspa1b, rad51, wrn and xpc. Rac1 deletion protected the liver from acute toxicity following doxorubicin treatment. Moreover, the level of S139 phosphorylated histone H2AX (?H2AX), which is indicative of DNA damage, and mRNA expression of pro-inflammatory (IL-6) and pro-fibrotic (CTGF, TGF?, ?SMA) factors were mitigated in rac1 knockout animals. By contrast, lack of rac1 promoted subacute hepatotoxicity, which was determined 3 weeks after injection of multiple low doses of doxorubicin by assaying the ?H2AX level, mitotic index and pro-fibrotic gene expression. Regarding ionizing radiation, rac1 deficiency had no major effects on DNA damage induction or acute pro-inflammatory and pro-fibrotic stress responses. Mice lacking hepatic rac1 for extended period of time (15 months) revealed increased mRNA expression of fibrosis-related factors (CTGF, TGF?, collagen, MMP1) and fibrotic tissue remodeling. In addition, protein expression of the senescence marker p16 was enhanced in the absence of rac1. Taken together, the data provide evidence that Rac1 is required for doxorubicin-induced DNA damage induction. It is also involved in both the acute and delayed inflammatory and fibrotic stress response in the liver following doxorubicin, but not ionizing radiation, treatment and, furthermore, protects against endogenous liver aging. PMID:23519127
Bopp, A; Wartlick, F; Henninger, C; Kaina, B; Fritz, G
Rac1 modulates acute and subacute genotoxin-induced hepatic stress responses, fibrosis and liver aging
To investigate the importance of the Ras-homologous GTPase Rac1 for the hepatic response to genotoxic insults and liver aging, rac1 was deleted in liver of mice by Mx1-Cre-based recombination. Knockout of rac1 caused complex changes in basal as well as doxorubicin and ionizing radiation-induced mRNA expression of various genotoxic stress response-related genes, including hspa1b, rad51, wrn and xpc. Rac1 deletion protected the liver from acute toxicity following doxorubicin treatment. Moreover, the level of S139 phosphorylated histone H2AX (?H2AX), which is indicative of DNA damage, and mRNA expression of pro-inflammatory (IL-6) and pro-fibrotic (CTGF, TGF?, ?SMA) factors were mitigated in rac1 knockout animals. By contrast, lack of rac1 promoted subacute hepatotoxicity, which was determined 3 weeks after injection of multiple low doses of doxorubicin by assaying the ?H2AX level, mitotic index and pro-fibrotic gene expression. Regarding ionizing radiation, rac1 deficiency had no major effects on DNA damage induction or acute pro-inflammatory and pro-fibrotic stress responses. Mice lacking hepatic rac1 for extended period of time (15 months) revealed increased mRNA expression of fibrosis-related factors (CTGF, TGF?, collagen, MMP1) and fibrotic tissue remodeling. In addition, protein expression of the senescence marker p16 was enhanced in the absence of rac1. Taken together, the data provide evidence that Rac1 is required for doxorubicin-induced DNA damage induction. It is also involved in both the acute and delayed inflammatory and fibrotic stress response in the liver following doxorubicin, but not ionizing radiation, treatment and, furthermore, protects against endogenous liver aging.
Bopp, A; Wartlick, F; Henninger, C; Kaina, B; Fritz, G
Prognostic value of hepatic venous pressure gradient measurements in alcoholic cirrhosis: A 10-year prospective study
BACKGROUND & AIMS: Different parameters are considered predictors of bleeding and death in alcoholic cirrhosis. The aim of this study was to establish the prognostic value of a prospective and sequential evaluation of portal pressure, variceal size, and Pugh's score in portal-hypertensive patients with alcoholic cirrhosis but no previous bleeding. METHODS: Thirty patients were evaluated for 42 +\\/- 5 months
J Vorobioff; RJ Groszmann; E Picabea; M Gamen; R Villavicencio; J Bordato; I Morel; M Audano; H Tanno; E Lerner; M Passamonti
Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state
Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but remaining unknown is whether functional differences in the hypothalamic-pituitary-adrenal (HPA) axis precede alcohol abuse and dependence or result from chronic exposure to this drug. Using an operant self-administration animal model of alcohol dependence and serial blood sampling, we show that long-term exposure to alcohol causes significant impairment of HPA function in adult male Wistar rats. Acute alcohol (voluntary self-administration or experimenter-administered) stimulated the release of corticosterone and its upstream regulator, adrenocorticotropic hormone, but chronic exposure sufficient to produce dependence led to a dampened neuroendocrine state. HPA responses to alcohol were most robust in ælow-respondingÆ non-dependent animals (averaging < 0.2 mg/kg/session), intermediate in non-dependent animals (averaging ~0.4 mg/kg/session), and most blunted in dependent animals (averaging ~1.0 mg/kg/session) following several weeks of daily 30-min self-administration sessions, suggesting that neuroendocrine tolerance can be initiated prior to dependence and relates to the amount of alcohol consumed. Decreased expression of corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus and reduced sensitivity of the pituitary to CRF may contribute to, but do not completely explain, neuroendocrine tolerance. The present results, combined with previous studies, suggest that multiple adaptations to stress regulatory systems may be brought about by excessive drinking, including a compromised hormonal response and a sensitized brain stress response that together contribute to dependence.
Richardson, Heather N.; Lee, Soon Y.; O'Dell, Laura E.; Koob, George F.; Rivier, Catherine L.
Does acute hepatitis C infection affect the central nervous system in HIV-1 infected individuals?
Central nervous system (CNS) manifestations of chronic hepatitis C virus (HCV) and chronic human immune deficiency virus-1 (HIV-1) infections have been reported, but the impact of acute HCV infection on the CNS is unknown. A total of 10 individuals with chronic stable HIV-1 with documented acute HCV (HCV-RNA polymerase chain reaction positive and HCV antibody negative, group 1) underwent cerebral proton magnetic resonance spectroscopy (MRS) using acquisition parameters to quantify myo-inositol/creatine (mI/Cr) ratio in the right basal ganglia (RBG). Two matched control groups also underwent MRS; group 2: ten with chronic HIV-1 and no evidence of HCV, and group 3: ten with no evidence of HIV or HCV. Subjects also underwent computerized neurocognitive assessments (CogState). RBG mI/Cr ratio in group 1 (acute HCV in a background of HIV) was significantly lower than that in groups 2 and 3 [2.90 (+/-0.7) vs 3.34 (+/-0.4) and 3.43 (+/-0.4), mean (SD) for group 1 vs 2 and 3 respectively, P = 0.049], with 50% of subjects in group 1 having a mI/Cr ratio below the lowest observed ratio in either of the other groups. On neurocognitive testing, significant defects in the monitoring domain were observed in group-1, compared with matched controls (P = 0.021). Acute HCV in HIV-1 infected subjects is associated with CNS involvement. Clinicians should be vigilant of early CNS involvement when assessing subjects with acute HCV. PMID:19780944
Winston, A; Garvey, L; Scotney, E; Yerrakalva, D; Allsop, J M; Thomson, E C; Grover, V P B; Main, J; Cox, J I; Wylezinska, M; Taylor-Robinson, S D
Octacosanol attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in rats intoxicated with carbon tetrachloride.
We examined whether octacosanol, the main component of policosanol, attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in rats intoxicated with carbon tetrachloride (CCl(4)). In rats intoxicated with CCl(4) (1 ml/kg, i.p.), the activities of serum transaminases increased 6 h after intoxication and further increased at 24 h. In the liver of CCl(4)-intoxicated rats, increases in lipid peroxide (LPO) concentration and myeloperoxidase activity and decreases in superoxixde dismutase activity and reduced glutathione (GSH) concentration occurred 6 h after intoxication and these changes were enhanced with an increase in xanthine oxidase activity and a decrease in catalase activity at 24 h. Octacosanol (10, 50 or 100 mg/kg) administered orally to CCl(4)-intoxicated rats at 6 h after intoxication attenuated the increased activities of serum transaminases and the increased hepatic myeloperoxidase and xanthine oxidase activities and LPO concentration and the decreased hepatic superoxide dismutase and catalase activities and GSH concentration found at 24 h after intoxication dose-dependently. Octacosanol (50 or 100 mg/kg) administered to untreated rats decreased the hepatic LPO concentration and increased the hepatic GSH concentration. These results indicate that octacosanol attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in CCl(4)-intoxicated rats. PMID:18385828
Ohta, Yoshiji; Ohashi, Koji; Matsura, Tatsuya; Tokunaga, Kenji; Kitagawa, Akira; Yamada, Kazuo
Octacosanol Attenuates Disrupted Hepatic Reactive Oxygen Species Metabolism Associated with Acute Liver Injury Progression in Rats Intoxicated with Carbon Tetrachloride
We examined whether octacosanol, the main component of policosanol, attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in rats intoxicated with carbon tetrachloride (CCl4). In rats intoxicated with CCl4 (1Āml/kg,Āi.p.), the activities of serum transaminases increased 6Āh after intoxication and further increased at 24Āh. In the liver of CCl4-intoxicated rats, increases in lipid peroxide (LPO) concentration and myeloperoxidase activity and decreases in superoxixde dismutase activity and reduced glutathione (GSH) concentration occurred 6Āh after intoxication and these changes were enhanced with an increase in xanthine oxidase activity and a decrease in catalase activity at 24Āh. Octacosanol (10, 50 or 100Āmg/kg) administered orally to CCl4-intoxicated rats at 6Āh after intoxication attenuated the increased activities of serum transaminases and the increased hepatic myeloperoxidase and xanthine oxidase activities and LPO concentration and the decreased hepatic superoxide dismutase and catalase activities and GSH concentration found at 24Āh after intoxication dose-dependently. Octacosanol (50 or 100Āmg/kg) administered to untreated rats decreased the hepatic LPO concentration and increased the hepatic GSH concentration. These results indicate that octacosanol attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in CCl4-intoxicated rats.
Ohta, Yoshiji; Ohashi, Koji; Matsura, Tatsuya; Tokunaga, Kenji; Kitagawa, Akira; Yamada, Kazuo
[The application of pulsed infrared laser radiation with autoresonant amplification for the treatment of patients with acute viral hepatitis B].
A group of 59 patients presenting with acute viral hepatitis B was available for examination. A single course of pulsed infrared laser irradiation with autoresonant amplification resulted in the improvement of clinical conditions of the patients and normalization of ALAT activity, total and direct bilirubin levels. PMID:21381326
Ba?galiev, A A
Perioperative acute phase response and outcome of hepatic resection, an experimental study.
Identification of patients at risk of postoperative complications could have an impact on the indications for a procedure as well as permitting modifications of treatment to reduce the surgical risk. This experimental study evaluated the correlation between peri-operative acute phase response and outcome of hepatic resection. The study was conducted on sixty healthy golden hamsters, which underwent partial hepatectomy. They were arranged in 3 groups (20 per each). One day prior to resection, fracture of the left hind leg was done in group I (G I) & wound infection had been created in group II (GII); while nothing done in group III (GIII) that acted as a control. Blood samples to estimate SGPT and serum albumin (as basic investigations for hamsters liver function) and serum IL-6 and CRP (as acute phase reactants) were taken preoperatively, immediately after resection and for the consecutive 3 days post operatively. The mean serum level of both acute phase reactants increased in GI and GII preoperatively and continues to rise immediately after resection. Post-operatively; among the three groups, the mean serum level of both reactants was higher in GI than in GII that was in turn higher than in GIII except when the postoperative complications were more severe than the other group, then this relation changed. PMID:24260813
Abbas, Mohamed; Farouk, Youssef; Hassan, Ahmed Abdelaziz; Hedaya, Mohamed Saied; Hamdy, Hussam; Ezzat, Hussein; Marei, Sayed; Arnaout, Hanaa Hamed; Nosseir, Mona; Eldamarawy, Mervat
Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection
Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection.
McElroy, Kerensa; Gaudieri, Silvana; Pham, Son T.; Chopra, Abha; Cameron, Barbara; Maher, Lisa; Dore, Gregory J.; White, Peter A.; Lloyd, Andrew R.
Cellular Immune Responses in Acute Hepatitis E Virus Infection to the Viral Open Reading Frame 2 Protein
Hepatitis E virus (HEV) causes acute viral hepatitis and is endemic in the developing world. Few data are available on cellular immune responses in HEV infection. Using flow cytometry, we studied the frequencies of peripheral blood CD4+/CD8+ T cells secreting interferon (IFN)-?, tumor necrosis factor (TNF)-?, and interleukin (IL)-4 in 21 patients with acute hepatitis E and 18 healthy controls, after stimulation with the HEV capsid (ORF2) protein. Cytokine levels in serum specimens and culture supernatants of ORF2-stimulated peripheral blood mononuclear cells (PBMCs) were estimated in enzyme-linked immunosorbent assays. In addition, cytokine mRNA transcripts were measured in PBMCs by reverse transcription-polymerase chain reaction. In patients with acute hepatitis E, although the total CD4+ population was expanded, the proportions of CD4+/CD69+ and CD8+/CD69+ cells producing IFN-?, TNF-?, and IL-4 in response to HEV ORF2 stimulation were unchanged. However, IFN-? levels in the supernatants and IFN-? mRNA transcripts in cells were elevated in ORF2-stimulated PBMCs in acute hepatitis E; levels of IL-2 or TNF-? were unchanged. Our findings suggest that CD4+ IFN-?-secreting cells, which do not belong either to the helper T cell type 1 or type 2 phenotype, as is the case with natural killer T cells, may be involved in the pathogenesis of hepatitis E. Further, the limited immune reactivity we detected in peripheral blood cells may be related to the sequestration of immune events to the intrahepatic compartment, which is the major disease site.
Cellular immune responses in acute hepatitis E virus infection to the viral open reading frame 2 protein.
Hepatitis E virus (HEV) causes acute viral hepatitis and is endemic in the developing world. Few data are available on cellular immune responses in HEV infection. Using flow cytometry, we studied the frequencies of peripheral blood CD4(+) /CD8(+) T cells secreting interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-4 in 21 patients with acute hepatitis E and 18 healthy controls, after stimulation with the HEV capsid (ORF2) protein. Cytokine levels in serum specimens and culture supernatants of ORF2-stimulated peripheral blood mononuclear cells (PBMCs) were estimated in enzyme-linked immunosorbent assays. In addition, cytokine mRNA transcripts were measured in PBMCs by reverse transcription-polymerase chain reaction. In patients with acute hepatitis E, although the total CD4(+) population was expanded, the proportions of CD4(+)/CD69(+) and CD8(+) /CD69(+) cells producing IFN-gamma, TNF-alpha, and IL-4 in response to HEV ORF2 stimulation were unchanged. However, IFN-gamma levels in the supernatants and IFN-gamma mRNA transcripts in cells were elevated in ORF2-stimulated PBMCs in acute hepatitis E; levels of IL-2 or TNF-alpha were unchanged. Our findings suggest that CD4(+) IFN-gamma-secreting cells, which do not belong either to the helper T cell type 1 or type 2 phenotype, as is the case with natural killer T cells, may be involved in the pathogenesis of hepatitis E. Further, the limited immune reactivity we detected in peripheral blood cells may be related to the sequestration of immune events to the intrahepatic compartment, which is the major disease site. PMID:17425421
Srivastava, Ruchi; Aggarwal, Rakesh; Jameel, Shahid; Puri, Pankaj; Gupta, Vijay K; Ramesh, V S; Bhatia, Shobna; Naik, Sita
Altered hepatic lipid metabolism in C57BL/6 mice fed alcohol: a targeted lipidomic and gene expression study[S
Chronic alcohol consumption is associated with fatty liver disease in mammals. The object of this study was to gain an understanding of dysregulated lipid metabolism in alcohol-fed C57BL/6 mice using a targeted lipidomic approach. Liquid chromatography tandem mass spectrometry was used to analyze several lipid classes, including free fatty acids, fatty acyl-CoAs, fatty acid ethyl esters, sphingolipids, ceramides, and endocannabinoids, in plasma and liver samples from control and alcohol-fed mice. The interpretation of lipidomic data was augmented by gene expression analyses for important metabolic enzymes in the lipid pathways studied. Alcohol feeding was associated with i) increased hepatic free fatty acid levels and decreased fatty acyl-CoA levels associated with decreased mitochondrial fatty acid oxidation and decreased fatty acyl-CoA synthesis, respectively; ii) increased hepatic ceramide levels associated with higher levels of the precursor molecules sphingosine and sphinganine; and iii) increased hepatic levels of the endocannabinoid anandamide associated with decreased expression of its catabolic enzyme fatty acid amide hydrolase. The unique combination of lipidomic and gene expression analyses allows for a better mechanistic understanding of dysregulated lipid metabolism in the development of alcoholic fatty liver disease.
Clugston, Robin D.; Jiang, Hongfeng; Lee, Man Xia; Piantedosi, Roseann; Yuen, Jason J.; Ramakrishnan, Rajasekhar; Lewis, Michael J.; Gottesman, Max E.; Huang, Li-Shin; Goldberg, Ira J.; Berk, Paul D.; Blaner, William S.
Effects of acute normovolemic hemodilution on splanchnic oxygenation and on hepatic histology and metabolism in anesthetized pigs.
Perioperative hemodilution (HD) has become an accepted means of reducing transfusion requirements. Therefore, the effects of limited (decrease in hematocrit [Hct] from 30 to 20%, "HD1") and severe (decrease in Hct from 20 to 14%, "HD2") acute normovolemic HD with 6% hydroxyethyl starch on splanchnic blood flows (electromagnetic flow probes), O2 uptakes and deliveries, surface O2 tensions (PO2) (Clark-type electrode), hepatic metabolism (organic acids), and hepatic histology (liver biopsies) were studied in nine pigs anesthetized and paralyzed with ketamine/flunitrazepam and pancuronium. HD1 caused significant (P less than 0.05) increases in cardiac output and all splanchnic flows. Only hepatic arterial blood flow increased twice as much as did cardiac output. Except for hepatic arterial O2 delivery, all splanchnic O2 deliveries decreased. Splanchnic O2 extractions increased, and O2 uptakes remained unchanged. There were no changes in mean surface PO2 values or in surface PO2 histograms of liver and small intestine; in portal or hepatic venous pH; and in hepatic uptake of pyruvate and lactate. In contrast, during HD2 (despite further increases in flows and O2 extractions) portal and hepatic venous pH decreased; mean surface PO2 of liver and small intestine decreased; and the liver surface PO2 histogram showed broadening and a shift to the left. However, hepatic uptake of lactate and pyruvate, and splanchnic O2 uptake remained unchanged, and histologic examination did not reveal significant cell injury. These data indicate that in this experimental model limited acute normovolemic HD was well tolerated by the splanchnic organs. After severe HD, gross liver function remained intact, but there was evidence that compensatory mechanisms (increases in flow and O2 extractions) were no longer fully able to counteract the decrease in splanchnic O2 delivery. PMID:1708653
N÷ldge, G F; Priebe, H J; Bohle, W; Buttler, K J; Geiger, K
Pure red-cell aplasia and autoimmune hemolytic anemia in a patient with acute hepatitis A
Pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) have rarely been reported as an extrahepatic manifestation of acute hepatitis A (AHA). We report herein a case of AHA complicated by both PRCA and AIHA. A 49-year-old female with a diagnosis of AHA presented with severe anemia (hemoglobin level, 6.9 g/dL) during her clinical course. A diagnostic workup revealed AIHA and PRCA as the cause of the anemia. The patient was treated with an initial transfusion and corticosteroid therapy. Her anemia and liver function test were completely recovered by 9 months after the initial presentation. We review the clinical features and therapeutic strategies for this rare case of extrahepatic manifestation of AHA.
Chang, Hyo Jeong; Cho, Sung Gyun; Oh, Tae Hoon; Jeon, Tae Joo; Shin, Won Chang; Choi, Won Choong
Dynamic Changes of Lipopolysaccharide Levels in Different Phases of Acute on Chronic Hepatitis B Liver Failure
Background High serum levels of lipopolysaccharide (LPS) with LPS-MD-2/TLR4 complex activated NF-kb and cytokine cause hepatic necrosis in animal models. We investigated the dynamic changes of LPS levels in patients with acute on chronic hepatitis B liver failure (ACHBLF). Methods We enrolled ACHBLF patients for a 12-week study. PatientsÆ LPS levels were measured along with 10 healthy controls. Patients on supportive care and recovered without intervention(s) were analyzed. PatientsÆ LPS levels during the disease progression phase, peak phase, and remission phase were compared with healthy controls. Results Among 30 patients enrolled, 25 who received interventions or expired during the study period were excluded from the analysis, five patients on supportive care who completed the study were analyzed. Significant abnormal distributions of LPS levels were observed in patients in different phases (0.0168▒0.0101 in progression phase; 0.0960▒0.0680 in peak phase; 0.0249▒0.0365 in remission phase; and 0.0201▒0.0146 in controls; respectively, p<0.05). The highest level of LPS was in the peak phase and significantly elevated when compared to controls (0.0201▒0.0146 vs. 0.0960▒0.0680, p?=?0.007). There were no statistically significant differences in LPS levels between healthy controls and subjects in the progression phase or remission phase. Dynamic changes of LPS were correlated with MELD-Na in the progression phase (p?=?0.01, R?=?0.876) and in the peak phase (p?=?0.000, R?=??1.00). Conclusions Significant abnormal distributions of LPS levels were observed in ACHBLF with the highest level in the peak phase. The dynamic changes of LPS were correlated with disease severity and suggested LPS causing secondary hepatic injury.
Zhang, Wei; Zheng, Yubao; Peng, Liang; Deng, Hong; Chen, Youming; Chen, Lubiao; Chen, Sui; Zhang, Min; Gao, Zhiliang
Acute liver injury induces nucleocytoplasmic redistribution of hepatic methionine metabolism enzymes.
Abstract Aims: The discovery of methionine metabolism enzymes in the cell nucleus, together with their association with key nuclear processes, suggested a putative relationship between alterations in their subcellular distribution and disease. Results: Using the rat model of d-galactosamine intoxication, severe changes in hepatic steady-state mRNA levels were found; the largest decreases corresponded to enzymes exhibiting the highest expression in normal tissue. Cytoplasmic protein levels, activities, and metabolite concentrations suffered more moderate changes following a similar trend. Interestingly, galactosamine treatment induced hepatic nuclear accumulation of methionine adenosyltransferase (MAT) ?1 and S-adenosylhomocysteine hydrolase tetramers, their active assemblies. In fact, galactosamine-treated livers showed enhanced nuclear MAT activity. Acetaminophen (APAP) intoxication mimicked most galactosamine effects on hepatic MAT?1, including accumulation of nuclear tetramers. H35 cells that overexpress tagged-MAT?1 reproduced the subcellular distribution observed in liver, and the changes induced by galactosamine and APAP that were also observed upon glutathione depletion by buthionine sulfoximine. The H35 nuclear accumulation of tagged-MAT?1 induced by these agents correlated with decreased glutathione reduced form/glutathione oxidized form ratios and was prevented by N-acetylcysteine (NAC) and glutathione ethyl ester. However, the changes in epigenetic modifications associated with tagged-MAT?1 nuclear accumulation were only prevented by NAC in galactosamine-treated cells. Innovation: Cytoplasmic and nuclear changes in proteins that regulate the methylation index follow opposite trends in acute liver injury, their nuclear accumulation showing potential as disease marker. Conclusion: Altogether these results demonstrate galactosamine- and APAP-induced nuclear accumulation of methionine metabolism enzymes as active oligomers and unveil the implication of redox-dependent mechanisms in the control of MAT?1 subcellular distribution. Antioxid. Redox Signal. 20, 2541-2554. PMID:24124652
Delgado, Miguel; Garrido, Francisco; Pķrez-Miguelsanz, Juliana; Pacheco, MarĒa; Partearroyo, Teresa; Pķrez-Sala, Dolores; Pajares, MarĒa Angeles
Brief motivational intervention for adolescents treated in emergency departments for acute alcohol intoxication - a randomized-controlled trial
Background Alcohol misuse among youth is a major public health concern and numbers of adolescents admitted to the emergency department for acute alcoholic intoxication in Germany are recently growing. The emergency setting offers an opportunity to reach at-risk alcohol consuming adolescents and provide brief interventions in a potential ōteachable momentö. However, studies on brief interventions targeting adolescents in emergency care are scarce and little is known about their effectiveness when delivered immediately following hospitalization for acute alcohol intoxication. In this protocol we present the HaLT-Hamburg trial evaluating a brief motivational intervention for adolescents treated in the emergency department after an episode of acute alcoholic intoxication. Methods The trial design is a parallel two-arm cluster randomized-controlled trial with follow-up assessment after 3 and 6 months. N?=?312 participants aged 17 years and younger will be recruited Fridays to Sundays in 6 pediatric clinics over a period of 30 months. Intervention condition is a manual-based brief motivational intervention with a telephone booster after 6 weeks and a manual-guided intervention for caregivers which will be compared to treatment as usual. Primary outcomes are reduction in binge drinking episodes, quantity of alcohol use on a typical drinking day and alcohol-related problems. Secondary outcome is further treatment seeking. Linear mixed models adjusted for baseline differences will be conducted according to intention-to-treat (ITT) and completers (per-protocol) principles to examine intervention effects. We also examine quantitative and qualitative process data on feasibility, intervention delivery, implementation and receipt from intervention providers, receivers and regular emergency department staff. Discussion The study has a number of strengths. First, a rigorous evaluation of HaLT-Hamburg is timely because variations of the HaLT project are widely used in Germany. Second, prior research has not targeted adolescents in the presumed teachable moment following acute alcohol intoxication. Third, we included a comprehensive process evaluation to raise external validity. Fourth, the study involved important stakeholders from the start to set up organizational structures for implementation and maintaining project impact. Trial registration Current Controlled Trials ISRCTN31234060 (April 30th 2012).
Alcohol Health and Research Journal, Volume 27, Number 3, 2003. Alcohol Liver Disease. Part 1: An Overview.
National Technical Information Service (NTIS)
Contents: The epidemiology of alcoholic liver disease; Relationships between nutrition, alcohol use, and liver disease; Hepatitis C and alcohol; Hepatic encephalopathy; Diagnosis and treatment of alcoholic liver disease and its complications; and Liver tr...
An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure
Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.
Tunon, Maria Jesus; Alvarez, Marcelino; Culebras, Jesus M; Gonzalez-Gallego, Javier
Genetic analysis of HAV strains recovered from patients with acute hepatitis from Southern Italy.
Southern Italy is an endemic area for HAV infection contributing to the majority of Italian hepatitis A cases. Using molecular analysis, HAV strains have been classified in distinct genotypes and subgenotypes. To characterize HAV wild-type strains circulating in Southern Italy, sequence analysis of VP3-VP1 and VP1/2A junction regions of HAV isolates recovered from 25 patients with acute hepatitis during 2000 and 2001 was carried out. HAV isolates showed a degree of identity, after pairwise comparison with one another, ranging from 91.9-100% in the VP3-VP1 junction region and 89.9-100% in the VP1/2A junction region. All strains belonged to genotype I, with 84% (21/25) of samples clustering in subgenotype IA and 16% (4/25) in subgenotype IB. Cocirculation of subgenotypes IA and IB was observed among isolates from 2000, whereas all strains from 2001 were subgenotype IA. In addition, the subgenotype IA strains formed different clusters, one of which was related closely to some Cuban strains, showing a percent similarity of 98.8% in the 168-base pair segment encompassing the VP1/2A junction and the same amino acid substitution. The latter finding suggests that this subgenotype variant circulates also in the Mediterranean area. The results of the phylogenetic analysis confirm the genetic heterogeneity among HAV strains in Western Europe. PMID:12766995
Chironna, Maria; Grottola, Antonella; Lanave, Cecilia; Villa, Erica; Barbuti, Salvatore; Quarto, Michele
Acute Hepatitis C in HIV-1 Infected Japanese Cohort: Single Center Retrospective Cohort Study
Objectives HCV co-infection is a poor prognostic factor in HIV-1-infected patients. Although the number of newly reported patients who show seroconversion is increasing, the clinical features are still unclear, especially in Asian countries. Design A single-center retrospective cohort study of patients diagnosed between 2001¢2012. Methods Acute hepatitis C (AHC) was diagnosed upon detection of high serum ALT (>100 IU) followed by anti-HCV seroconversion. Clinical characteristics, HIV-1-related immunological status and IL-28B genotypes (rs12979860, rs8099917) were collected. We compared these variables between patients with and without spontaneous clearance of HCV and between responders and non-responders to treatment with pegylated interferon (PEG-IFN) plus ribavirin. Results Thirty-five patients were diagnosed with AHC during the study period. The majority (96.9%) were MSM. Three were lost to follow-up. Seventy-five percent of patients with AHC (24/32) were asymptomatic and found incidentally to have high serum ALT. Compared to those who did not show spontaneous clearance, patients with spontaneous HCV viral clearance showed more symptoms and more severe abnormalities related to acute hepatitis. Spontaneous clearance was seen in 4 out of 28 patients with CC+TT genotype, but not in 6 patients with IL-28B CT+TG genotype. PEG-IFN plus ribavirin treatment was initiated in 12 out of 28 cases without spontaneous clearance. The sustained virological response rate was high (81.8%, 9/11), even in cases with CT+TG genotype infected with HCV genotype 1b (SVR 2/2). Conclusions Careful attention to AHC is needed in HIV-1-infected MSM. Early diagnosis and PEG-IFN plus ribavirin treatment should be considered for AHC cases.
Ishikane, Masahiro; Watanabe, Koji; Tsukada, Kunihisa; Nozaki, Yuichi; Yanase, Mikio; Igari, Toru; Masaki, Naohiko; Kikuchi, Yoshimi; Oka, Shinichi; Gatanaga, Hiroyuki
Ecological momentary assessment of acute alcohol use disorder symptoms: Associations with mood, motives, and use on planned drinking days.
Several theories posit that alcohol is consumed both in relation to one's mood and in relation to different motives for drinking. However, there are mixed findings regarding the role of mood and motives in predicting drinking. Ecological momentary assessment (EMA) methods provide an opportunity to evaluate near real-time changes in mood and motives within individuals to predict alcohol use. In addition, endorsement of criteria of an alcohol use disorder (AUD) may also be sensitive to changes within subjects. The current study used EMA with 74 moderate drinkers who responded to fixed and random mood, motive, alcohol use, and AUD criteria prompts over a 21-day assessment period. A temporal pattern of daytime mood, evening drinking motivation, and nighttime alcohol use and acute AUD symptoms on planned drinking days was modeled to examine how these associations unfold throughout the day. The results suggest considerable heterogeneity in drinking motivation across drinking days. Additionally, an affect regulation model of drinking to cope with negative mood was observed. Specifically, on planned drinking days, the temporal association between daytime negative mood and the experience of acute AUD symptoms was mediated via coping motives and alcohol use. The current study found that motives are dynamic, and that changes in motives may predict differential drinking patterns across days. Further, the study provides evidence that emotion-regulation-driven alcohol involvement may need to be examined at the event level to fully capture the ebb and flow of negative affect motivated drinking. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID:24932896
Dvorak, Robert D; Pearson, Matthew R; Day, Anne M
How CAGE, RAPS4-QF, and AUDIT Can Help Practitioners for Patients Admitted with Acute Alcohol Intoxication in Emergency Departments?
Aims: To help clinicians to identify the severity of alcohol use disorders (AUDs) from optimal thresholds found for recommended scales. Especially, taking account of the high prevalence of alcohol dependence among patients admitted to the emergency department (ED) for acute alcohol intoxication (AAI), we propose to define thresholds of severity of dependence based on the AUDIT score. Methods: All patients admitted to the ED with AAI (blood alcohol level >0.8?g/L), in a 2-month period, were assessed using the CAGE, RAPS-QF, and AUDIT, with the alcohol dependence/abuse section of the mini international neuropsychiatric interview (MINI) used as the gold standard. To explore the relation between the AUDIT and the MINI the sum of the positive items on the MINI (dependence) as a quantitative variable and as an ordinal parameter were analyzed. From the threshold score found for each scale we proposed intervals of severity of AUDs. Results: The mean age of the sample (122 males, 42 females) was 46?years. Approximately 12% of the patients were identified with alcohol abuse and 78% with dependence (DSM-IV). Cut points were determined for the AUDIT in order to distinguish mild and moderate dependence from severe dependence. A strategy of intervention based on levels of severity of AUD was proposed. Conclusion: Different thresholds proposed for the CAGE, RAPS4-QF, and AUDIT could be used to guide the choice of intervention for a patient: brief intervention, brief negotiation interviewing, or longer more intensive motivational intervention.
Brousse, Georges; Arnaud, Benjamin; Geneste, Julie; Pereira, Bruno; De Chazeron, Ingrid; Teissedre, Frederique; Perrier, Christophe; Schwan, Raymund; Malet, Laurent; Schmidt, Jeannot; Llorca, Pierre Michel; Cherpitel, Cheryl J.
Co-circulation of genotype IA and new variant IB hepatitis A virus in outbreaks of acute hepatitis in Hungary--2003/2004.
Hepatitis A virus (HAV) is one of the most important causes of acute infectious hepatitis worldwide. In Hungary, the reported number of HAV infections has been decreasing in the last four decades, nevertheless, still, each year 500-800 new cases and multiple outbreaks occur, particularly in the northeast region of Hungary. In Hungary, serology is used routinely to establish the diagnosis of HAV infection without genetic analysis of HAV strains for molecular epidemiology. In this study, serum samples collected from symptomatic patients were tested by enzyme-immunoassay (anti-HAV-IgM ELISA) to establish the cause of three acute hepatitis A outbreaks (outbreak 1--from low prevalence region in Southwest Hungary in 2003 and outbreaks 2 and 3 from the endemic region in Northeast Hungary in 2004). Outbreak strains were characterized by reverse transcription-polymerase chain reaction (RT-PCR) amplification of a 360 bp viral VP1/2A region, amplicon sequencing and phylogenetic analysis. Four, seven, and three sera from outbreaks 1, 2, and 3, respectively, were investigated by RT-PCR for HAV genome and HAV RNA was detected in 4 (100%), 4 (57%), and 2 (67%) samples. All strains belonged to genotype I HAV. Outbreak 1 was caused by the new variant subtype IB and outbreaks 2 and 3 caused by genetically identical subtype IA strains. The Hungarian IA and IB hepatitis A viruses had the highest nucleotide identity, 98.4% and 99.0%, to IT-SCH-00 and IT-MAR-02 strains, respectively, detected in year 2000 and 2002 in Italy. Endemic subtype IA and probably imported new variant subtype IB HAV viruses was detected in outbreaks of hepatitis in Hungary that are closely related genetically to HAV strains in Italy. PMID:16998889
Reuter, Gßbor; Juhßsz, Agnes; Kosztolßnyi, Lßszl¾nķ; Lefler, Eva; Fekete, Zsuzsanna
A randomized controlled trial of lamivudine to treat acute hepatitis B.
The role of antivirals in patients with acute viral hepatitis B (AVH-B) has not been evaluated in controlled trials. The aim of this study was to evaluate the efficacy of lamivudine in patients with AVH-B. AVH-B patients with serum bilirubin of more than 5 mg/dL were randomized to receive either 100 mg of lamivudine daily for 3 months (group 1, n = 31) or placebo (group 2, n = 40). Patients were considered to have severe AVH-B if they fulfilled 2 of 3 criteria: (1) hepatic encephalopathy; (2) serum bilirubin > or = 10.0 mg/dL; and (3) international normalized ratio (INR) > or = 1.6. At week 4, HBV DNA levels were significantly lower (P = 0.037) in group 1 (median: 3.6721 log copies/mL) than group 2 (median: 4.2721 log copies/mL). Thereafter, HBV DNA levels were comparable in the 2 groups. The improvement in serum bilirubin, ALT, and INR values was similar in the 2 groups. Twenty-two patients (71%) in group 1 and 25 patients (62.5%) in group 2 had severe AVH-B. Results were similar when patients with severe AVH-B were analyzed separately. After 12 and 18 months, 93.5% and 92.5%, respectively, of patients in the lamivudine group and 96.7% and 97.5%, respectively, of patients in the placebo group lost HBsAg. There were no deaths in either group. After 1 year, 21 patients (67.7%) in group 1 and 34 patients (85%) in group 2 developed protective anti-HBs titers (P = 0.096). All HBeAg-positive patients in both groups lost e antigen and anti-HBe developed in 71% and 87.5% of patients in groups 1 and 2, respectively (P = 0.132). Conclusion: Though lamivudine causes a greater decrease in levels of HBV DNA, it does not cause significantly greater biochemical and clinical improvement as compared to placebo in patients with acute hepatitis B. PMID:17187417
Kumar, M; Satapathy, S; Monga, R; Das, K; Hissar, S; Pande, C; Sharma, B C; Sarin, S K
Acute alcohol intoxication prolongs neuroinflammation without exacerbating neurobehavioral dysfunction following mild traumatic brain injury.
Traumatic brain injury (TBI) represents a leading cause of death and disability among young persons with ?1.7 million reported cases in the United States annually. Although acute alcohol intoxication (AAI) is frequently present at the time of TBI, conflicting animal and clinical reports have failed to establish whether AAI significantly impacts short-term outcomes after TBI. The objective of this study was to determine whether AAI at the time of TBI aggravates neurobehavioral outcomes and neuroinflammatory sequelae post-TBI. Adult male Sprague-Dawley rats were surgically instrumented with gastric and vascular catheters before a left lateral craniotomy. After recovery, rats received either a primed constant intragastric alcohol infusion (2.5?g/kg+0.3?g/kg/h for 15?h) or isocaloric/isovolumic dextrose infusion followed by a lateral fluid percussion TBI (?1.4?J, ?30?ms). TBI induced apnea and a delay in righting reflex. AAI at the time of injury increased the TBI induced delay in righting reflex without altering apnea duration. Neurological and behavioral dysfunction was observed at 6?h and 24?h post-TBI, and this was not exacerbated by AAI. TBI induced a transient upregulation of cortical interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1 mRNA expression at 6?h, which was resolved at 24?h. AAI did not modulate the inflammatory response at 6?h but prevented resolution of inflammation (IL-1, IL-6, tumor necrosis factor-?, and MCP-1 expression) at 24?h post-TBI. AAI at the time of TBI did not delay the recovery of neurological and neurobehavioral function but prevented the resolution of neuroinflammation post-TBI. PMID:24050411
Teng, Sophie X; Molina, Patricia E
Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report.
The clinical data of a patient with acute-on-chronic liver failure were analyzed retrospectively. The patient has suffered from hepatitis B for 30 years. His liver function deteriorated, yielding Child-Pugh grade C and reaching a model for end-stage liver disease score of 33 points within a short period; this condition was complicated with highly active variceal bleeding and coagulation system failure (PT > 100 s). The patient also presented hepatocellular carcinoma. Comprehensive treatments included effective inhibition of hepatitis B virus replication and intensive care support. Piggyback orthotopic liver transplantation was performed as the final treatment. The patient recovered uneventfully and was discharged after surgery. PMID:24810647
Li, Lei; Liu, Yimei; Luo, Tiancheng; Zhou, Jian; Hou, Yingyong; Shen, Xizhong; Wang, Jiyao
Outcome of an outbreak of acute hepatitis C among healthy volunteers participating in pharmacokinetics studies.
We identified 15 patients with acute hepatitis C (AHC) among 29 healthy volunteers participating in 2 consecutive pharmacokinetics studies. Molecular techniques were used to determine the relatedness of viral strains, whereas clinical and virologic follow-up was started to establish the course and outcome of the acute infection. After presentation, serum liver enzymes and HCV RNA were monitored weekly for 4 months, then monthly for at least 12 months. Liver biopsy was performed 6 to 12 months after AHC diagnosis. Phylogenetic analysis of coding regions for the envelope glycoproteins E1 and E2 was performed. At presentation, all 15 patients tested HCV RNA-positive and had HCV genotype 2c. Phylogenetic analysis indicated a common source of infection. Fourteen patients agreed to be followed prospectively. Infection resolved spontaneously in 8 patients, HCV RNA becoming undetectable by 4 to 5 months after the presumed time of infection in 5 of them and by 8, 13, and 24 months in the remaining 3. Six patients developed chronic infection. Liver biopsies performed in 9 subjects who were HCV RNA-positive 6 months after AHC diagnosis revealed that the prevalent histologic finding was lobular inflammation. In conclusion, our homogeneous cohort showed a wide spectrum of clinical, virologic and histologic features, and, more importantly, short-term outcome differed noticeably despite the common source of infection. PMID:12297849
Larghi, Alberto; Zuin, Massimo; Crosignani, Andrea; Ribero, Maria Lisa; Pipia, Cristina; Battezzati, Pier Maria; Binelli, Giorgio; Donato, Francesco; Zanetti, Alessandro Remo; Podda, Mauro; Tagger, Alessandro
Silymarin suppresses hepatic stellate cell activation in a dietary rat model of non-alcoholic steatohepatitis: Analysis of isolated hepatic stellate cells
Non-alcoholic steatohepatitis (NASH) is characterized by hepatocellular injury and initial fibrosis severity has been suggested as an important prognostic factor of NASH. Silymarin was reported to improve carbon tetrachloride-induced liver fibrosis and reduce the activation of hepatic stellate cells (HSC). We investigated whether silymarin could suppress the activation of HSCs in NASH induced by methionine- and choline-deficient (MCD) diet fed to insulin-resistant rats. NASH was induced by feeding MCD diet to obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were fed with standard chow and served as the control. OLETF rats were fed on either standard laboratory chow, or MCD diet or MCD diet mixed with silymarin. Histological analysis of the liver showed improved non-alcoholic fatty liver disease (NAFLD) activity score in silymarin-fed MCD-induced NASH. Silymarin reduced the activation of HSCs, evaluated by counting ?-smooth muscle actin (SMA)-positive cells and measuring ?-SMA mRNA expression in the liver lysates as well as in HSCs isolated from the experimental animals. Although silymarin decreased ?1-procollagen mRNA expression in isolated HSCs, the anti-fibrogenic effect of silymarin was not prominent so as to show significant difference under histological analysis. Silymarin increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and decreased tumor necrosis factor (TNF)-? mRNA expression in the liver. Our study suggested that the possible protective effect of silymarin in diet induced NASH by suppressing the activation of HSCs and disturbing the role of the inflammatory cytokine TNF-?.
Human immunodeficiency virus, hepatitis C, and inflammatory biomarkers in individuals with alcohol problems: a cross-sectional study
Background Assessing whether hepatitis C (HCV) co-infection with human immunodeficiency virus (HIV) is associated with increased inflammation is complex. The liver, integral to inflammatory biomarker synthesis, is compromised by HCV and alcohol abuse. Using single liver-synthesized biomarkers (e.g. C-reactive protein) to represent inflammation may not be appropriate in HIV/HCV co-infection. We hypothesized that 1) detectable HIV/HCV RNA was independently associated with increased inflammation; 2) a composite inflammation measure describes inflammation differently from single inflammatory biomarkers. Methods We compared inflammation by HIV/HCV group in a cohort of 361 HIV infected participants from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study. Inflammatory biomarkers >75th percentile were considered elevated. Associations between HIV/HCV group and elevated biomarkers were analyzed as a composite measure (inflammatory burden) or individually. We defined inflammatory burden as number of concurrently elevated biomarkers. Biomarkers included interleukin-6 (IL-6), C-reactive protein (CRP), cystatin C, serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-?), interleukin-10 (IL-10). Covariates: alcohol, liver fibrosis, comorbidities, CD4 count, antiretroviral therapy, substance use. Results Detectable HIV and HCV RNA (OR?=?2.49; 95% CI?=?1.05¢5.89) and detectable HCV RNA alone (2.95; 1.08¢8.01) were independently associated with increased odds of having a greater inflammatory burden compared to undetectable viremia. Elevated IL-10 (7.79; 1.90¢31.97) and TNF-? (7.70; 1.42¢41.83) were independently associated with detectable HIV and HCV RNA. Elevated IL-10 was also associated with detectable HCV RNA alone (5.51; 1.17, 25.84). Conclusions Detectable HIV and HCV replication versus undetectable replication was associated with inflammatory burden and certain inflammatory biomarkers independently of alcohol consumption, liver fibrosis and other comorbidities.
Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model
Background & Aims In this study, we sought to determine the temporal relationship between hepatic mitochondrial dysfunction, hepatic steatosis and insulin resistance, and to examine their potential role in the natural progression of non-alcoholic fatty liver disease (NAFLD) utilising a sedentary, hyperphagic, obese, Otsuka Long¢Evans Tokushima Fatty (OLETF) rat model. Methods OLETF rats and their non-hyperphagic control Long¢Evans Tokushima Otsuka (LETO) rats were sacrificed at 5, 8, 13, 20, and 40 weeks of age (n = 6¢8 per group). Results At 5 weeks of age, serum insulin and glucose and hepatic triglyceride (TG) concentrations did not differ between animal groups; however, OLETF animals displayed significant (p < 0.01) hepatic mitochondrial dysfunction as measured by reduced hepatic carnitine palmitoyl-CoA transferase-1 activity, fatty acid oxidation, and cytochrome c protein content compared with LETO rats. Hepatic TG levels were significantly elevated by 8 weeks of age, and insulin resistance developed by 13 weeks in the OLETF rats. NAFLD progressively worsened to include hepatocyte ballooning, perivenular fibrosis, 2.5-fold increase in serum ALT, hepatic mitochondrial ultrastructural abnormalities, and increased hepatic oxidative stress in the OLETF animals at later ages. Measures of hepatic mitochondrial content and function including ?-hydroxyacyl-CoA dehydrogenase activity, citrate synthase activity, and immunofluorescence staining for mitochondrial carbamoyl phosphate synthetase-1, progressively worsened and were significantly reduced at 40 weeks in OLETF rats compared to LETO animals. Conclusions Our study documents that hepatic mitochondrial dysfunction precedes the development of NAFLD and insulin resistance in the OLETF rats. This evidence suggests that progressive mitochondrial dysfunction contributes to the natural history of obesity-associated NAFLD.
Rector, R. Scott; Thyfault, John P.; Uptergrove, Grace M.; Morris, E. Matthew; Naples, Scott P.; Borengasser, Sarah J.; Mikus, Catherine R.; Laye, Matthew J.; Laughlin, M. Harold; Booth, Frank W.; Ibdah, Jamal A.
Acute Effects of 3,4-Methylenedioxymethamphetamine (MDMA) on Behavioral Measures of Impulsivity: Alone and in Combination with Alcohol
The use of 3,4-methylenedioxymethamphetamine (MDMA) has frequently been associated with increased levels of impulsivity during abstinence. The effects of MDMA on measures of impulsivity, however, have not yet been studied during intoxication. The present study was designed to assess the acute effects of MDMA and alcohol, alone and in combination, on behavioral measures of impulsivity and risk-taking behavior. A total
Johannes G Ramaekers; Kim P C Kuypers
Acute steatohepatitis, due to extreme metabolic dysregulation, as the first presentation of non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is a slowly progressive chronic disease, with a high prevalence among obese, dyslipidemic or diabetic people, commonly presented as an asymptomatic mild elevation of serum aminotransferases. We report a patient who experienced an acute form of non-alcoholic steatohepatitis, as the first manifestation of NAFLD, due to exacerbation of pre-existing metabolic disorders by an extremely unhealthy lifestyle. A 50-year old, obese, diabetic man presented with a one-week history of jaundice and malaise. Analysis revealed elevated liver enzymes, bilirubin, lipids, and glucose. Based on patient's history, physical examination, laboratory results, and imaging findings, acute non-alcoholic steatohepatitis was established as a diagnosis of exclusion. The patient was started on a low-calorie diet free of carbohydrates and fats, in combination with insulin. A dramatic improvement of clinical and laboratory parameters was observed. In the context of extreme metabolic dysregulation, induced by unhealthy diet, NAFLD may present as an acute steatohepatitis. PMID:24765505
Kranidiotis, Georgios; Angelidi, Angeliki; Sevdalis, Emmanouel; Telios, Thomas-Nikolaos; Gougoutsi, Alexandra; Melidonis, Andreas
Effect of alcohol on hepatic receptor of high density lipoproteins (HDL)
Moderate alcohol intake has been shown to increase HDL cholesterol and proteins. The seemingly protective effect' of moderate alcohol drinking against cardiovascular diseases has been attributed to an increase in serum HDL. In this study, the authors show that a receptor for HDL is present in rat liver. Rat liver membrane was prepared by stepwise ultracentrifugation. Apo Al was iodinated using {sup 125}I-NaI and IODO-beads. HDL was labeled by incubating with {sup 125}I-apo Al then refloated be centrifugation. Binding of {sup 125}I-HDL to rat liver membrane reached equilibrium by 2-3 h and was saturable at 37C. The binding was inhibited 80% by excess unlabeled HDL, but was inhibited only 25% by excess LDL. It could also be inhibited by preincubating HDL with anti-apo Al or anti-apo E antisera but not with anti-apo AIV or control sera. The binding affinity of HDL to the liver membrane of rats fed alcohol for 5 wk was 50% that of their pair-fed controls. Thus a decrease in the binding of HDL to liver membrane due to alcohol-drinking may result in a slower clearance of HDL by the liver and consequently a higher HDL concentration in the serum.
Lin, R.C.; Miller, B.M. (Indiana Univ., Indianapolis (United States) V.A. Medical Center, Indianapolis, IN (United States))
Symptomatic Acute Hepatitis C in Egypt: Diagnosis, Spontaneous Viral Clearance, and Delayed Treatment with 12 Weeks of Pegylated Interferon Alfa-2a
Background and ObjectivesThe aim of this study was to estimate the proportion of spontaneous viral clearance (SVC) after symptomatic acute hepatitis C and to evaluate the efficacy of 12 weeks of pegylated interferon alfa-2a in patients who did not clear the virus spontaneously.MethodsPatients with symptomatic acute hepatitis C were recruited from two ōfever hospitalsö in Cairo, Egypt. Patients still viremic
Noha Sharaf Eldin; Soheir Ismail; Hala Mansour; Claire Rekacewicz; Moustafa El-Houssinie; Sherif El-Kafrawy; Saeed El Aidi; Mohamed Abdel-Hamid; Gamal Esmat; Stanislas Pol; Arnaud Fontanet; Mostafa K. Mohamed; Brett Lindenbach
Alcoholic liver disease: roles of alcohol and malnutrition.
A toxic effect of alcohol is the principal cause of the development of liver disease in alcoholism. Fatty infiltration of the liver is a consequence of ethanol metabolism due mainly to an increased synthesis and decreased degradation of fatty acids. Mechanisms that have been suggested for ethanol-induced hepatocellular necrosis include centrolobular hypoxia due to an increased oxygen requirement and intracellular accumulation of protein, fat, and water which results in increased cell size. Hepatocellular necrosis, however, may not be a necessary stage in the development of cirrhosis. Chronic ethanol administration increases hepatic collagen deposition, and acute and chronic ethanol administration inhibit liver cell regeneration. Increased humoral and cellular immunological activity to liver tissue and its components may contribute to the persistence of liver disease in the alcoholic. However, only a small proportion of alcoholics and baboons fed alcohol develop cirrhosis, suggesting that other factors, either genetic, environmental, or nutritional, play a role. Malnutrition is common in alcoholics. Liver disease is more common in some malnourished populations, and has been produced by nutrient deficiencies. Decreased dietary intake, as well as malabsorption and alterations in the metabolism of nutrients, are causes of nutrient deficiencies in alcoholism. Some of the effects of alcohol on the liver may be mediated by its actions on nutrient absorption and metabolism. PMID:7001889
Mezey, E
Milk Thistle for Alcoholic and\\/or Hepatitis B or C Liver DiseasesŚA Systematic Cochrane HepatoBiliary Group Review with Meta-Analyses of Randomized Clinical Trials
OBJECTIVES:Our objectives were to assess the beneficial and harmful effects of milk thistle (MT) or MT constituents versus placebo or no intervention in patients with alcoholic liver disease and\\/or hepatitis B and\\/or C liver diseases.METHODS:Randomized clinical trials studying patients with alcoholic and\\/or hepatitis B or C liver diseases were included (December 2003). The randomized clinical trials were evaluated by components
Andrea Rambaldi; Bradly P. Jacobs; Gaetano Iaquinto; Christian Gluud
Hepatoprotective and anti-hepatitis C viral activity of Platycodon grandiflorum extract on carbon tetrachloride-induced acute hepatic injury in mice.
The present study aims to evaluate the anti-HCV activity of hotwater extract from Platycodon grandiflorum (BC703) with HCV genotype 1b subgenomic replicon system and investigate its hepatoprotective activity on carbon tetrachloride (CCl(4))-induced acute liver damage in mice. BC703 produced significant hepatoprotective effects against CCl(4)-induced acute hepatic injury by decreasing the activities of serum enzymes, nitric oxide and lipid peroxidation. Histopathological studies further substantiated the protective effect of BC703. Furthermore, BC703 inhibited the HCV RNA replication with an EC(50) value and selective index (CC(50)/EC(50)) of 2.82 Ąg/mL and above 35.46, respectively. However, digested BC703 using a simulated gastric juice showed poor protective effect against CCl(4)-induced hepatotoxicity in mice and decreased anti-HCV activity as compared to the intact BC703. Although further studies are necessary, BC703 may be a beneficial agent for the management of acute hepatic injury and chronic HCV infection. PMID:22878389
Kim, Tae-Won; Lim, Jong-Hwan; Song, In-Bae; Park, Sang-Jin; Yang, Jae-Won; Shin, Jung Cheul; Suh, Joo-Won; Son, Hwa-Young; Cho, Eun-Sang; Kim, Myoung-Seok; Lee, Sang-Wook; Kim, Jong-Woo; Yun, Hyo-In
Successful management of hepatic mucormycosis in an acute lymphoblastic leukaemia patient: a case report and review of the literature.
We present a case of hepatic mucormycosis in a 9-year-old boy with acute lymphoblastic leukaemia. Despite long-term use of combined liposomal amphotericin B and posaconazole therapy, the lesion persisted and could only be treated by surgical excision. After surgery, antifungal treatment was continued with posaconazole. On follow-up, the patient had two episodes of ascending cholangitis which were responsive to intravenous antibiotics. He is doing well at the moment in remission for 2.5Āyears. Mucormycosis was long regarded as a fatal infection with poor prognosis. With early medical and surgical management, survival rates increase. Isolated hepatic mucormycosis is rare and only seven cases were reported in the literature up to now. We wanted to emphasise the role of early surgery in patients with hepatic mucormycosis in view of the literature. PMID:24635874
Tuysuz, Gulen; Ozdemir, Nihal; Senyuz, Osman Faruk; Emre, Senol; Kantarcioglu, Serda; Adaletli, Ibrahim; Kepil, Nuray; Tutuncu, Cigdem; Celkan, Tiraje
Symptomatic Acute Hepatitis C in Egypt: Diagnosis, Spontaneous Viral Clearance, and Delayed Treatment with 12 Weeks of Pegylated Interferon Alfa-2a
Background and Objectives The aim of this study was to estimate the proportion of spontaneous viral clearance (SVC) after symptomatic acute hepatitis C and to evaluate the efficacy of 12 weeks of pegylated interferon alfa-2a in patients who did not clear the virus spontaneously. Methods Patients with symptomatic acute hepatitis C were recruited from two ōfever hospitalsö in Cairo, Egypt. Patients still viremic three months after the onset of symptoms were considered for treatment with 12 weeks of pegylated interferon alfa-2a (180 Ąg/week). Results Between May 2002 and February 2006, 2243 adult patients with acute hepatitis were enrolled in the study. The SVC rate among 117 patients with acute hepatitis C was 33.8% (95%CI [25.9%¢43.2%]) at three months and 41.5% (95%CI [33.0%¢51.2%]) at six months. The sustained virological response (SVR) rate among the 17 patients who started treatment 4¢6 months after onset of symptoms was 15/17?=?88.2% (95%CI [63.6%¢98.5%]). Conclusion Spontaneous viral clearance was high (41.5% six months after the onset of symptoms) in this population with symptomatic acute hepatitis C. Allowing time for spontaneous clearance should be considered before treatment is initiated for symptomatic acute hepatitis C.
Sharaf Eldin, Noha; Ismail, Soheir; Mansour, Hala; Rekacewicz, Claire; El-Houssinie, Moustafa; El-Kafrawy, Sherif; El Aidi, Saeed; Abdel-Hamid, Mohamed; Esmat, Gamal; Pol, Stanislas; Fontanet, Arnaud; Mohamed, Mostafa K.
Scoring systems predict the prognosis of acute-on-chronic hepatitis B liver failure: an evidence-based review.
Acute-on-chronic hepatitis B liver failure is a devastating condition that is associated with mortality rates of over 50% and is consequent to acute exacerbation of chronic hepatitis B in patients with previously diagnosed or undiagnosed chronic liver disease. Liver transplantation is the definitive treatment to lower mortality rate, but there is a great imbalance between donation and potential recipients. An early and accurate prognostic system based on the integration of laboratory indicators, clinical events and some mathematic logistic equations is needed to optimize treatment for patients. As parts of the scoring systems, the MELD was the most common and the donor-MELD was the most innovative for patients on the waiting list for liver transplantation. This review aims to highlight the various features and prognostic capabilities of these scoring systems. PMID:24762209
Wu, Fa-Ling; Shi, Ke-Qing; Chen, Yong-Ping; Braddock, Martin; Zou, Hai; Zheng, Ming-Hua
Acute and chronic effects of alcohol use on organizational processes in memory
Tested 24 25-50 yr old males selected on the basis of their drinking histories (alcoholics, heavy drinkers, and social drinkers) on a series of tasks assessing organizational processes in memory. Each S was tested once while sober and once while intoxicated (blood alcohol level = 100 mg%). No systematic differences emerged as a function of drinking history, but alcohol intoxication
Linda J. Rosen; Catherine L. Lee
Exendin?4, a glucagon?like peptide?1 receptor agonist, modulates hepatic fatty acid composition and ??5?desaturase index in a murine model of non?alcoholic steatohepatitis.
Glucagon?like peptide?1Ā(GLP?1) is involved in the development of non?alcoholic steatohepatitisĀ(NASH), which is characterized by fatty acid imbalance. The aim of this study was to investigate the effects of the GLP?1 receptorĀ(GLP?1R) agonist, exendin?4Ā(Ex?4), on hepatic fatty acid metabolism and its key enzyme, ??5?desaturase, in a murine model of NASH. NASH was induced in db/db mice fed a methionine?choline deficientĀ(MCD) diet. Ex?4 (n=4) or saline [controlĀ(CON); n=4] was administered intraperitoneally for 8Āweeks. Steatohepatitis activity was evaluated by non?alcoholic fatty liver diseaseĀ(NAFLD) activity score. Hepatic fatty acid composition and ??5?desaturase index were analyzed by gas chromatography. Ex?4 treatment significantly reduced body weight and the NAFLD activity score. Hepatic concentrations of long?chain saturated fatty acidsĀ(SFAs) were significantly higher in the Ex?4 group compared to the CON group (23240▒955Āvs.Ā31710▒8436ĀĄg/gĢliver, P<0.05).Ex?4 significantly reduced hepatic n?3 polyunsaturated fatty acidĀ(PUFA)/n?6 PUFA ratio compared to the CON group (13.83▒3.15Āvs.Ā8.73▒1.95, P<0.05). In addition, the hepatic ??5?desaturase index was significantly reduced in the Ex?4 group compared to the CON group (31.1▒12.4Āvs.Ā10.5▒3.1, P<0.05). In conclusion, the results showed that Ex?4 improved steatohepatitis in a murine model of NASH. Furthermore, Ex?4 altered hepatic long?chain saturated and PUFA composition and reduced the ??5?desaturase index. Thus, Ex?4 may improve NASH by regulating hepatic fatty acid metabolism. PMID:24993337
Kawaguchi, Takumi; Itou, Minoru; Taniguchi, Eitaro; Sata, Michio
A Novel Multiplex Real-Time PCR Assay for the Concurrent Detection of Hepatitis A, B and C Viruses in Patients with Acute Hepatitis
A novel multiplex real-time PCR assay for concurrent detection of hepatitis viruses was evaluated for its clinical performance in screening patients with acute hepatitis. A total of 648 serum samples were collected from patients with acute symptoms of hepatitis. Concurrent detection of nucleic acids of HAV, HBV and HCV was performed using the MagicplexÖ HepaTrio Real-time Detection test. Serum nucleic acid levels of HBV and HCV were also quantified by the Cobas« AmpliPrep/Cobas« TaqMan« (CAP/CTM) HBV and HCV tests. PatientsÆ medical records were also reviewed. Concordance rates between the results from the HepaTrio and the CAP/CTM tests for the detection of HBV and HCV were 94.9% (k?=?0.88) and 99.2% (k?=?0.98), respectively. The cycle threshold values with the HepaTrio test were also correlated well with the levels of HBV DNA (r?=??0.9230) and HCV RNA (r?=??0.8458). The sensitivity and specificity of the HepaTrio test were 93.8% and 98.2%, respectively, for detecting HBV infection, and 99.1% and 100.0%, respectively, for HCV infection. For the HepaTrio test, 21 (3.2%) cases were positive for both HBV and HCV. Among the positive cases, 6 (0.9%) were true coinfections. This test also detected 18 (2.8%) HAV positives. The HepaTrio test demonstrated good clinical performance and produced results that agreed well with those of the CAP/CTM assays, especially for the detection of HCV. This assay was also able to detect HAV RNA from anti-HAV IgM-positive individuals. Therefore, this new multiplex PCR assay could be useful for the concurrent detection of the three hepatitis viruses.
Park, Yongjung; Kim, Beom Seok; Choi, Kyu Hun; Shin, Dong Ho; Lee, Mi Jung; Cho, Yonggeun; Kim, Hyon-Suk
Seroconversion to hepatitis C virus alternate reading frame protein during acute infection
The existence of hepatitis C virus proteins encoded by alternate reading frames overlapping the core-encoding region has been suggested. Several mechanisms of production have been postulated and the function(s) of these proteins in the HCV life cycle remain(s) unknown. We analyzed cases of seroconversion to an alternate reading frame protein in a group of 17 patients infected by the one of two hepatitis C virus genotype 1b strains during an outbreak in a hemodialysis unit. Three patients seroconverted and antibodies were transiently detected in another patient. Three of these patients were infected by one of the two HCV strains, whereas the strain infecting the remaining patient could not be identified. Quasispecies sequence analysis of the core-coding region showed no differences in the core or +1 reading frame sequences that could explain alternate reading frame protein seroconversion in some but not all of the patients infected by one of the HCV strains, and no such difference was found between the two strains. As differences in the structure of RNA elements could play a role in frameshift events, we conducted a predictive analysis of RNA folding by using RNAfold software. No difference was found between the patients who did and did not seroconvert to alternate reading frame protein. Conclusion our findings prove that alternate reading frame proteins can be produced during acute HCV infection. However, seroconversion does not occur in all patients for unknown reasons. Alternate reading frame protein could be generated by minority quasispecies variants or variants that occur transiently.
Morice, Yoann; Ratinier, Maxime; Miladi, Ahmed; Chevaliez, Stephane; Germanidis, Georgios; Wedemeyer, Heiner; Laperche, Syria; Lavergne, Jean-Pierre; Pawlotsky, Jean-Michel
By 1970, the hepatitis B virus had been identified and shown to be a major cause of acute and chronic liver disease. Reliable but ... insensitive tests for the virus were newly available. Hepatitis B was the most common cause of acute liver ...
High genomic similarity between European type hepatitis E virus subgenotype 3e strains isolated from an acute hepatitis patient and a wild boar in Mie, Japan.
A 67-year-old male living in Tsu city, Mie prefecture, Japan was referred to our hospital for further examination of acute liver injury and was diagnosed as having clinical hepatitis E virus (HEV) infection in January 2010. The HEV strain (HE-JA11-1701) isolated from the patient belonged to genotype 3 and European-type subgenotype 3e. It was presumed that the patient had been infected from a wild boar (Sus scrofa leucomystax) because he consumed meat/viscera from a wild boar that he had captured himself as a hunter approximately 2 months before disease onset. A specimen of the boar meat/viscera that the patient had ingested was not available. However, the HE-JA11-1701 strain was 99.8% identical within the 412-nucleotide sequence of the open reading frame 2 region to a HEV strain (JBOAR012-Mie08) that had been recovered from a wild boar captured near the patient's hunting area in 2008. A phylogenetic analysis confirmed that the two HEV strains had a close genetic relationship and were segregated into subgenotype 3e, supported by a high bootstrap value of 99%. Of note, the HE-JA11-1701 and JBOAR012-Mie08 strains were remotely related to the 3e strains reported in Japan and European countries, with a nucleotide difference of 7.9-13.9%, reinforcing the uniqueness of the 3e strains obtained in the present study. These results strongly support our speculation that the patient developed acute hepatitis E via consumption of HEV-infected boar meat/viscera. Genetic analyses of HEV strains are useful for tracing infectious sources in sporadic cases of acute hepatitis E. PMID:23639180
Okano, Hiroshi; Nakano, Tatsunori; Sugimoto, Kazushi; Takahashi, Kazuaki; Nagashima, Shigeo; Takahashi, Masaharu; Arai, Masahiro; Okamoto, Hiroaki
Fatty acid ethyl esters: markers of alcohol abuse and alcoholism.
Chronic alcoholism, which is associated with hepatic, pancreatic, and myocardial diseases, is one of the major health problems in the United States with high morbidity and mortality. Many individuals who abuse alcohol chronically die even before reaching the clinical stage of the disease. Reliable biomarkers of the diseases induced by chronic alcohol abuse, as well as for alcoholism, currently are not available. In the current study, we measured plasma concentrations of fatty acid ethyl esters [(FAEEs), nonoxidative metabolites of ethanol] in 39 patients with a detectable concentration of alcohol in their blood samples. In turn, we determined the relation of FAEE concentrations with blood alcohol concentration (BAC). Of 39 patients in whom we evaluated this relation, only five had a history of chronic alcohol abuse, and six had a history of acute alcohol abuse. Patients' age ranged from 25 to 71 years. Within this age range, greater concentrations of FAEEs were found in the plasma samples obtained from patients in the 41- to 50-year age group. There were no sex-related differences in BAC, nor in FAEE concentrations. Thirteen patients had a BAC greater than 300 mg%. For 11 patients, the BAC ranged between 200 and 299 mg%, and, for 12 patients, the BAC ranged between 100 and 199 mg%. In comparison with findings for patients with a BAC that ranged between 100 and 299 mg%, the FAEE concentrations were approximately twofold higher in patients with a BAC greater than 300 mg%. Ethyl palmitate and ethyl oleate were the main FAEEs detected in most patients. In general, FAEE concentrations increased with increasing BAC. However, in comparison with patients with a history of acute alcohol abuse, a greater increase in total FAEE concentrations was observed in patients with a history of chronic alcohol abuse (4,250 ng/ml and 15,086 ng/ml, respectively). Fatty acid ethyl esters were either detected in trace amounts or not detectable in the plasma of control subjects with no known alcohol ingestion. These results support our hypothesis that nonoxidative metabolism of ethanol to FAEEs is an important pathway of ethanol disposition during chronic alcohol abuse, and that FAEE concentrations can be a more reliable biomarker of chronic alcohol abuse than a history of acute alcohol abuse. PMID:15902908
Kaphalia, Bhupendra S; Cai, Ping; Khan, M Firoze; Okorodudu, Anthony O; Ansari, G A S
Citric acid reduces the decline in P300 amplitude induced by acute alcohol consumption in healthy adults*
Event-related potential (ERP) is a reliable neuroelectric measure of brain activity that helps to confirm the assessment of mental status and cognitive impairment. Many studies have reported that alcoholics show a significantly lower ERP P300 amplitude than the norm. In the present study, ERP P300 waves were measured to evaluate the effect of citric acid on cognitive function during excessive alcohol consumption in healthy adults. Five volunteers were selected through clinical interview, physical examination, and psychiatric assessment for participation in this study. In a double-blind placebo-controlled before-after design, each subject was treated with 5 ml/kg body weight alcohol, 5 ml/kg body weight alcohol and 1 mg citric acid, or a placebo on three separate occasions, one week apart. ERP P300, blood biochemical indicators, blood alcohol concentrations (BACs) and acetaldehyde concentrations were assessed. Repeated measure analysis of variance (ANOVA) with a within-subjects factor was used to evaluate differences in blood biochemical indicators, BACs, blood acetaldehyde concentrations, and ERP P300 in the three sessions of assessments. Several blood biochemical indicators showed significant differences between treatments, including the levels of cholinesterase (CHE), total bile acid (TBA), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and glycylproline dipeptidyl aminopeptidase (GPDA). BACs after consumption of alcohol alone or citric acid with alcohol were significantly higher compared to those after placebo treatment (P<0.05). There were no significant differences in blood acetaldehyde concentrations between the treatments. The P300 amplitudes on the frontal (Fz), central (Cz), and parietal (Pz) regions of the scalp after consumption of alcohol were significantly lower than those after consumption of the placebo or citric acid with alcohol (P<0.05), while there were no significant differences between the latter two treatments. The results of this study suggest that citric acid could reduce the decline in ERP P300 amplitude and cognitive ability induced by acute alcohol consumption. It may also affect some blood biochemical indicators, but the specific mechanisms need further research.
Chen, Wei-xing; Xu, Chuan-qin; Chen, Shao-hua; Xu, Gen-yun; Ye, Huai-zhuang
Serum from patients with hepatitis E virus-related acute liver failure induces human liver cell apoptosis
The pathogenesis of acute liver failure has not been fully elucidated. The present study investigated the effects of the serum from patients with hepatitis E virus (HEV)-related acute liver failure on human liver cell survival and apoptosis, and evaluated the protective effects of anti-lipopolysaccharide(LPS) antibody recognizing core polysaccharide against acute liver failure serum-induced apoptosis. Serum was collected from patients with HEV-related acute liver failure. The levels of endotoxin (LPS) in the serum were measured using a quantitative tachypleus amebocyte lysate endotoxin detection kit with a chromogenic endpoint. Serum with a mean concentration of LPS was incubated with L02 human liver cells and the rate of apoptosis was detected by flow cytometry. The apoptotic rate was also evaluated in liver cells incubated with antibody and the HEV-related acute liver failure serum. The results indicated that the concentration of LPS in the serum of patients with HEV-related acute liver failure was 0.26▒0.02 EU/ml, which was significantly higher than that of the control group (P<0.05). The rate of apoptosis in the human liver cells induced by acute liver failure serum was 5.83▒0.42%, which was significantly increased compared with that in the cells treated with the serum of healthy individuals (P<0.05). The apoptotic rate of the cells incubated with antibody and the acute liver failure serum was 5.53▒0.51%, which was lower than that of the cells incubated with acute liver failure serum alone (P>0.05). These results indicate that the serum of patients with HEV-related acute liver failure induces the apoptosis of human liver cells. LPS may be directly involved in the apoptosis of human liver cells. Moreover, the presence of the antibody did not significantly reduce the level of apoptosis of liver cells exposed to HEV-related acute liver failure serum.
Serum Hepatic Enzyme Activity and Alcohol Drinking Status in Relation to the Prevalence of Metabolic Syndrome in the General Japanese Population
Background Studies on the combined associations of elevated serum hepatic enzyme activity and alcohol drinking with metabolic syndrome are rare. Our objectives were to evaluate the associations of elevated serum hepatic enzyme activity with the prevalence of metabolic syndrome in the general Japanese population and whether alcohol drinking had a modifying effect on these associations. Methods We conducted a cross-sectional study with 1,027 men and 1,152 women throughout Japan during 2002¢2010. Biochemical factors including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were determined in overnight fasting blood, and a survey on lifestyle was conducted by questionnaire. Serum ALT and GGT levels were divided into tertiles in men and women, and their associations with the prevalence of metabolic syndrome were evaluated by logistic regressions. Results Elevated serum ALT and GGT, even within the reference range, were independently associated with increased metabolic syndrome prevalence and were associated with most of its components in both sexes, except for the association between GGT and low high-density lipoprotein (HDL) cholesterol in men. Stratified analyses by alcohol drinking status revealed that within the same tertile category of serum ALT and GGT, subjects classified as alcohol abstainers showed higher adjusted odds ratios for metabolic syndrome prevalence than those classified as regular alcohol drinkers in both sexes. The interaction effects of serum GGT with alcohol drinking status on metabolic syndrome prevalence were significant in both sexes. Conclusions These results suggest that elevated serum ALT and GGT, even within the reference range, are independently associated with increased metabolic syndrome prevalence, especially in alcohol abstainers, in Japanese men and women.
Uemura, Hirokazu; Katsuura-Kamano, Sakurako; Yamaguchi, Miwa; Sawachika, Fusakazu; Arisawa, Kokichi
A prospective study of the influence of acute alcohol intoxication versus chronic alcohol consumption on outcome following traumatic brain injury.
The purpose of the study was to disentangle the relative contributions of day-of-injury alcohol intoxication and pre-injury alcohol misuse on outcome from TBI. Participants were 142 patients enrolled from a Level 1 Trauma Center (in Vancouver, Canada) following a traumatic brain injury (TBI; 43 uncomplicated mild TBI and 63 complicated mild-severe TBI) or orthopedic injury [36 trauma controls (TC)]. At 6-8 weeks post-injury, diffusion tensor imaging (DTI) of the whole brain was undertaken using a Phillips 3T scanner. Participants also completed neuropsychological testing, an evaluation of lifetime alcohol consumption (LAC), and had blood alcohol levels (BALs) taken at the time of injury. Participants in the uncomplicated mild TBI and complicated mild-severe TBI groups had higher scores on measures of depression and postconcussion symptoms (d = 0.45-0.83), but not anxiety, compared with the TC group. The complicated mild-severe TBI group had more areas of abnormal white matter on DTI measures (all p < .05; d = 0.54-0.61) than the TC group. There were no difference between groups on all neurocognitive measures. Using hierarchical regression analyses and generalized linear modeling, LAC and BAL did provide a unique contribution toward the prediction of attention and executive functioning abilities; however, the variance accounted for was small. LAC and BAL did not provide a unique and meaningful contribution toward the prediction of self-reported symptoms, DTI measures, or the majority of neurocognitive measures. In this study, BAL and LAC were not predictive of mental health symptoms, postconcussion symptoms, cognition, or white-matter changes at 6-8 weeks following TBI. PMID:24964748
Lange, Rael T; Shewchuk, Jason R; Rauscher, Alexander; Jarrett, Michael; Heran, Manraj K S; Brubacher, Jeffrey R; Iverson, Grant L
Hepatic Artery and Portal Vein Doppler Indexes in Non-alcoholic Fatty Liver Disease Before and After Treatment to Prevent Unnecessary Health Care Costs
Background: We tested whether hepatic haemodynamics assessed by Doppler ultrasonography can be a predictor of response to therapy in patients with non-alcoholic fatty liver disease (NAFLD) to prevent further unnecessary diagnostic tests and interventions. Methods: Forty eight consecutive patients affected by NAFLD, who refered to some clinics in Tabriz, Iran between 2009 and 2011 were included in the study. Response to therapy was assessed by decrease in liver enzyme levels. Three liver Doppler parameters (hepatic artery resistance index [RI], hepatic artery pulsatility index [PI] and portal vein waveform [PVW]) were analysed in all subjects who showed a decrease in liver function tests results. Wilcoxon and paired student's t-test were used for analysis. Results: Forty eight subjects with NAFLD were included in the study during 21 months, out of which 22 (39.1% male - mean age: 37.6 ▒ 8.3) responded to the treatment and formed the basis of this study. Mean hepatic artery RI increased significantly from 0.60 ▒ 0.07 to 0.83 ▒ 0.27before and after treatment, however, there was no significant differences between hepatic artery PI or PVW. Conclusions: Increase in hepatic artery RI assessed by Doppler ultrasound may provide information on improvement of NAFLD in patients during the course of therapy.
Tarzamni, Mohammad Kazem; Khoshbaten, Manouchehr; Sadrarhami, Shohreh; Daneshpajouhnejad, Parnaz; Jalili, Javad; Gholamian, Masoud; Shahmoradi, Zahra
Liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis.
Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the U.K. Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation. PMID:21618697
Dowman, Joanna K; Gunson, Bridget K; Mirza, Darius F; Bramhall, Simon R; Badminton, Mike N; Newsome, Philip N
Liver Transplantation for Acute Intermittent Porphyria is Complicated by a High Rate of Hepatic Artery Thrombosis
Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the UK Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation. Liver Transpl 18:195¢200, 2012. ® 2011 AASLD.
Dowman, Joanna K; Gunson, Bridget K; Mirza, Darius F; Bramhall, Simon R; Badminton, Mike N; Newsome, Philip N