title: Effects of Metformin, Pioglitazone, and Silymarin Treatment on Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Pilot Study Hepatic effects of dietary weight loss in morbidly obese subjects. Effect of silymarin plus vitamin E in patients with non-alcoholic fatty liver disease. A randomized clinical pilot study. The Pharmacokinetics of Silymarin Is Altered in Patients with Hepatitis C Virus and Nonalcoholic Fatty Liver Disease and Correlates with Plasma Caspase-3/7 Activity Preventive use of a hepatoprotectant against anti-tuberculosis drug-induced liver injury: A randomized controlled trial. Serum Oxidative Stress Markers and Lipidomic Profile to Detect NASH Patients Responsive to an Antioxidant Treatment: A Pilot Study Spirulina platensis versus silymarin in the treatment of chronic hepatitis C virus infection. A pilot randomized, comparative clinical trial A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. Silymarin in treatment of non-alcoholic steatohepatitis: A randomized clinical trial. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. Effects of Silybum marianum on serum hepatitis C virus RNA, alanine aminotransferase levels and well-being in patients with chronic hepatitis C. Use of the Romanian product Silimarina in the treatment of chronic liver diseases. Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results. Effects of silybum marianum on patients with chronic hepatitis C A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. Effects of Mediterranean diet supplemented with silybin–vitamin E–phospholipid complex in overweight patients with non-alcoholic fatty liver disease One year follow-up of patients treated with misoprostol in acute phase of viral hepatitis B. Silybin Treatment is Associated With Reduction in Serum Ferritin in Patients With Chronic Hepatitis C Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease.
abstract: Background Nonalcoholic fatty liver disease ( NAFLD ) is one of the most common reasons of enzyme increase in liver . In About 10 percent of patients with NAFLD , the disease progresses toward Non Alcoholic Steatohepatitis ( NASH ) and about one third of them may progress toward cirrhosis , liver dysfunction , and even hepatocellular carcinoma . Objectives According to high prevalence of NAFLD and the fact that there is no consensus on treatment of this disease , the aim of this study was to assess the effects of metformin , pioglitazone , and silymarin on treatment of NAFLD . Patients and Methods Sixty six patients with NAFLD who were presented in the Endocrinology and Metabolism clinic of Boo’ali Hospital , Qazvin , Iran , were assigned r and omly into three groups ( n = 22 ) . First group was treated by pioglitazone 15 mg/d , second group by metformin 500 mg/d , and third group by silymarin 140 mg/d . All patients underwent clinical and biochemical evaluations including weight , fasting blood sugar ( FBS ) , lipid profiles , body mass index ( BMI ) , aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , and serum insulin levels in pre- and post-intervention after eight-week follow up . Results Before the treatment there was no significant difference between three groups with respect to average age , BMI and gender , FBS , lipid profile , AST , ALT , serum insulin level , and Homeostasis Model Assessment ( HOMA ) index for insulin resistance . After the intervention , a significant reduction was observed in average amount of FBS , lipid profile , ALT , AST , serum insulin level and HOMA index in three groups ( P < 0.01 ) . The most reduction in average FBS , TG , serum insulin level , and HOMA index was observed in pioglitazone group , the most reduction in average amount of cholesterol was seen in metformin group , and the most decrease in average amount of AST and ALT occurred in silymarin group . Conclusions These results suggest that all drugs are beneficial in improving biochemical indices in patients with NAFLD . Changes in AST and ALT in silymarin group were demonstrated more than that in other groups and the average difference between changes was significant between silymarin and metformin groups This prospect i ve study was carried out in order to evaluate the influence on liver morphology and function of a very-low-calorie formula diet .  Fourty-one morbidly obese , non-alcoholic subjects had liver biopsy performed before and after a median weight loss of 34 kg . Fatty change improved ( p less than 0.001 ) , but 24 % of the patients developed slight portal inflammation ( p = 0.039 ) or slight portal fibrosis ( p = 0.063 ) . Patients developing portal fibrosis had a higher degree of fatty change at entry ( p = 0.029 ) , a more pronounced reduction of fatty change ( p = 0.014 ) and a faster weight loss ( p = 0.026 ) . Liver biochemistry , which was of no individual diagnostic value , improved . It is concluded that morbidly obese subjects with a high degree of hepatic fatty change are at risk of developing portal inflammation and fibrosis when undergoing very fast dietary weight reductions OBJECTIVE Non-alcoholic fatty liver disease ( NAFLD ) is an increasingly recognized health problem . Various treatment strategies such as thiazolidinediones , metformin , lipid-lowering agents and antioxidants have been evaluated . So far , no single intervention has convincingly improved liver histology . Experience of using silymarin alone or in combination with other agents in patients with NAFLD is limited in the medical literature . The present study was conducted to evaluate the efficacy of silymarin plus vitamin E in the treatment of NAFLD . PATIENTS AND METHODS A sample of 36 patients was enrolled . The diagnosis of NAFLD was confirmed by percutaneous liver biopsy . All patients were r and omized to one of the following intervention groups : group I : treated with 2 tablets per day of silymarin plus vitamin E ( Eurosil 85 ® , MEDAS SL ) and a lifestyle modification program consisting of hypocaloric diet ( 1520 kcal , 52 % of carbohydrates , 25 % of lipids and 23 % of proteins ) and exercise for 3 months and group II ( only with the hypocaloric diet )  . Anthropometric variables as waist circumference , weight , body mass index ( BMI ) were measured . Biochemical parameters : Glucose , triglycerides , AST , ALT , GGt levels and insulin resistance ( HOMA-IR ) were determined under fasting conditions . Non-invasive NAFLD-index were applied before and after the treatments : Fatty liver index ( FLI ) , liver accumulation product ( LAP ) and NAFLD-Fibrosis score ( FS ) . RESULTS The mean age was 47.4 ± 11.2 years old ( range 18 - 67 ) ; 22 men and 14 women . In group I , 11 patients ( 61 % ) have a NAS-score > 5 and 10 ( 55.5 % ) in the group II ( NS ) . Anthropometric parameters decreased after treatment in both groups . Patients in both groups showed a decrease in GGt levels after treatment ( group I : 68 IU/L vs. 46.2 ± 27 IU/L ; p < 0.05 and group II 80.5 ± 46 IU/L vs. 50.3 ± 27 IU/L ; p < 0.05 ) . Only in group II we observed a significant decrease in AST and ALT levels . In both groups , we observed a decrease in : FLI index ( group I : 86.2 ± 19 vs. 76.9 + 20 ; p < 0.05 and in group II : 85.2 ± 18 vs. 77.5 ± 23 ; p < 0.05 ) , and NAFLD-FS index ( group I : -1.6 ± 1.8 vs. -2.1 ± 1.5 ; p < 0.05 and in group II -1 ± 1.9 vs. -1.5 ± 2.1 ; p < 0.05 ) . Patients in group I who did not get a 5 % loss of weight also displayed decreased GGt levels , and in the FLI and NAFLD-FS indexes ; whereas patients in group II without decrease of 5 % by weight showed no improvement in any of the analyzed parameters . CONCLUSIONS Treatment with silymarin plus vitamin E and a hypocaloric diet ameliorate function hepatic test , and non-invasive NAFLD index . Silymarin can be an alternative valid therapeutic option particularly when other drugs are not indicated or have failed or as a complementary treatment associated with other therapeutic programs Silymarin , used by 30 to 40 % of liver disease patients , is composed of six major flavonolignans , each of which may contribute to silymarin 's hepatoprotective properties . Previous studies have only described the pharmacokinetics for two flavonolignans , silybin A and silybin B , in healthy volunteers . The aim of this study was to determine the pharmacokinetics of the major silymarin flavonolignans in liver disease patients . Healthy volunteers and three patient cohorts were administered a single , 600-mg p.o . dose of milk thistle extract , and 14 blood sample s were obtained over 24 h. Silybin A and B accounted for 43 % of the exposure to the sum of total silymarin flavonolignans in healthy volunteers and only 31 to 38 % in liver disease cohorts as a result of accumulation of silychristin ( 20–36 % ) . Area under the curve ( AUC0–24h ) for the sum of total silymarin flavonolignans was 2.4- , 3.3- , and 4.7-fold higher for hepatitis C virus ( HCV ) noncirrhosis , nonalcoholic fatty liver disease ( p ≤ 0.03 ) , and HCV cirrhosis cohorts ( p ≤ 0.03 ) , respectively , compared with healthy volunteers ( AUC0–24h = 2021 ng · h/ml ) . Caspase-3/7 activity correlated with the AUC0–24h for the sum of all silymarin conjugates among all subjects ( R2 = 0.52 ) and was 5-fold higher in the HCV cirrhosis cohort ( p ≤ 0.005 versus healthy ) . No correlation was observed with other measures of disease activity , including plasma alanine aminotransferase , interleukin 6 , and 8-isoprostane F2α , a measure of oxidative stress . These findings suggest that the pharmacokinetics of silymarin is altered in patients with liver disease . Patients with cirrhosis had the highest plasma caspase-3/7 activity and also achieved the highest exposures for the major silymarin flavonolignans BACKGROUND AND AIM Hepatoprotectants are routinely prescribed in China to prevent anti-tuberculosis drug-induced liver injury ( ATLI ) . However , their biological mechanisms have not yet been clearly demonstrated . This study aims to evaluate the preventive effects of Silybum marianum against drug-induced liver injury among tuberculosis patients and to provide clinical guidelines for tuberculosis management in China . METHODS A r and omized controlled trial was performed in Jiangsu , China . Tuberculosis patients were r and omly allocated to the experimental group ( anti-tuberculosis therapy plus S. marianum capsule ) or the control group ( anti-tuberculosis therapy plus vitamin C tablet ) . The primary outcomes were the occurrence of probable and possible ATLI , the peak aspartate aminotransferase/alanine aminotransferase ratio and the maximum altered alkaline phosphatase or gamma-glutamyl transferase . RESULTS The final analysis comprised 183 cases in the experiment group and 187 cases in the control group . The risk of developing probable ATLI was not significantly different between the two groups . During the follow-up period , 43.72 % of cases in the experiment group and 35.83 % of cases in the control group were determined to have possible ATLI ( relative risk = 1.23 , 95 % confidence interval : 0.94 - 1.54 ) . When using a more strict definition of possible ATLI , the adjusted relative risk ( 95 % confidence interval ) was 1.76 ( 1.14 - 2.56 ) . The risks of adverse drug reactions , prolonged treatment length , taking second-line tuberculosis drugs , and the clearance of tuberculosis bacteria were similar between the two groups . CONCLUSIONS No significant preventive effect of silymarin was found for either lowering the risk of liver injury or boosting the positive outcomes . Worse , we even found a potential risk of liver damage caused by the hepatoprotectant Liver steatosis can evolve to steatohepatitis ( NASH ) through a series of biochemical steps related to oxidative stress in hepatocytes . Antioxidants , such as silybin , have been proposed as a treatment of patients with nonalcoholic fatty liver disease ( NAFLD ) and NASH . In this study , we evaluated , in patients with histologically documented NASH , the oxidant/antioxidant status and lipid “ fingerprint ” in the serum of NASH patients , both in basal conditions and after 12 months of treatment with silybin-based food integrator Realsil ( RA ) . The oxidant/antioxidant status analysis showed the presence of a group of patients with higher basal severity of disease ( NAS scores 4.67 ± 2.5 ) and a second group corresponding to borderline NASH ( NAS scores = 3.8 ± 1.5 ) . The chronic treatment with RA  changed the NAS score in both groups that reached the statistical significance only in group 2 , in which there was also a significant decrease of serum lipid peroxidation . The lipidomic profile showed a lipid composition similar to that of healthy subjects with a restoration of the values of free cholesterol , lysoPC , SM , and PC only in group 2 of patients after treatment with RA . Conclusion . These data suggest that lipidomic and /or oxidative status of serum from patients with NASH could be useful as prognostic markers of response to an antioxidant treatment Background Spirulina platensis , a cynobacterium used frequently as a dietary supplement had been found to exhibit many immune-stimulating and antiviral activities . It had been found to activate macrophages , NK cells , T cells , B cells , and to stimulate the production of Interferon gamma ( IFN-γ ) and other cytokines . Natural substances isolated from Spirulina platensis had been found to be potent inhibitors against several enveloped viruses by blocking viral absorption/penetration and some replication stages of progeny viruses after penetration into cells . We aim ed to study whether this dietary supplement possesses any therapeutically feasible activity worthy of further larger controlled clinical evaluation . Methods Sixty six patients with chronic hepatitis C virus infection and eligible for inclusion had been r and omized to either Spirulina or Silymarin treated groups for a period of six months treatment . The two groups were followed up and blindly compared for early ( after 3 months ) and end of 6 months treatment virological response . The effects of both treatments on each of alanine aminotransferase ( ALT ) , Chronic Liver Disease Question naire scores ( CLDQ ) , Arizona Sexual Experience Scale scores ( ASEX ) and the occurrence of any attributable adverse events were also compared . Results Among the 30 patients who had been treated with Spirulina and completed the 6 months protocol , 4 patients ( 13.3 % ) had a complete end of treatment virological response and 2 patients ( 6.7 % ) had a partial end of treatment response defined as significant decrease of virus load of at least 2-logs10 . Though the proportion of responders in Spirulina group was greater than in the Silymarin group , the difference was not statistically significant at the end of both 6 months ( p = 0.12 ) and 3 months treatment ( p = 0.22 ) by Exact test . Alanine aminotransferase as well as CLDQ and ASEX scores were found to be more significantly improved in Spirulina than in Silymarin treated group . Conclusions Our results could suggest a therapeutically feasible potential for Spirulina platensis in chronic HCV patients , worthy to conduct a larger sized and longer study to confirm these safety and efficacy encouraging results .Trial Registration WHO Clinical Trial Registration ID : ACTRN12610000958088http://apps.who.int/trial search /trial.aspx?trialid = Background Hepatitis is a common adverse effect of antituberculosis drugs . Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown . We aim ed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury ( antiTB-DILI ) in patients with tuberculosis . Methods A double-blind r and omized placebo-controlled trial was performed . Tuberculosis patients were r and omly allocated to receive placebo or silymarin . The outcomes of interests were antiTB-DILI and the maximum liver enzymes at week 4 . Antioxidative enzymes ( i.e. , superoxide dismutase ( SOD ) , glutathione and malondialdehyde assays ) were assessed . The risks of antiTB-DILI between the two groups were compared . A number need to treat was estimated . Results A total of 55 out of 70 expected numbers of patients were enrolled . There were 1/27 ( 3.7 % ) and 9/28 ( 32.1 % ) patients who developed antiTB-DILI in the silymarin and the placebo groups . Risk reduction was 0.28 ( 0.10 , 0.47 ) , i.e. , receiving silymarin was 28 % at lower risk for antiTB-DILI than placebo . This led to prevention of 28 patients from being antiTB-DILI among 100 treated patients . Median ( IQR ) of ALT levels at week 4 in the placebo and the silymarin group were 35.0 ( 15 , 415 ) IU/L and 31.5 ( 20 , 184 ) IU/L ( p = 0.455 ) . The decline of SOD level at week 4 in the silymarin group was less than the placebo group ( p < 0.027 ) . Conclusions Silymarin reduced the incidence of antiTB-DILI . The benefit of silymarin may be explained from superoxide dismutase restoration . Larger clinical trials are required to confirm the result of our small study [ Clinical trials . Gov Identifier Nct01800487 ] CONTEXT The botanical product silymarin , an extract of milk thistle , is commonly used by patients to treat chronic liver disease , despite scant and conflicting evidence of its efficacy . OBJECTIVE To determine the effect of silymarin on liver disease activity in patients with chronic hepatitis C virus ( HCV ) infection unsuccessfully treated with interferon-based therapy . DESIGN , SETTING , AND PARTICIPANTS Multicenter , double-blind , placebo-controlled trial conducted at 4 medical centers in the United States . Participants included 154 persons with chronic HCV infection and serum alanine aminotransferase ( ALT ) levels of 65 U/L or greater who were previously unsuccessfully treated with interferon-based therapy . Enrollment began in May 2008 and was completed in May 2010 , with the last follow-up visit completed in March 2011 . INTERVENTION Participants were r and omly assigned to receive 420-mg silymarin , 700-mg silymarin , or matching placebo administered 3 times per day for 24 weeks . MAIN OUTCOME MEASURES The primary outcome measure was serum ALT level of 45 U/L or less ( considered within the normal range ) or less than 65 U/L , provided this was at least a 50 % decline from baseline values . Secondary outcomes included changes in ALT levels , HCV RNA levels , and quality -of-life measures . RESULTS After 24 weeks of treatment , only 2 participants in each treatment group ( P ≥ .99 ) met the primary outcome measure ( 3.8 % [ 95 % CI , 0.5 % to 13.2 % ] for placebo , 4.0 % [ 95 % CI , 0.5 % to 13.7 % ] for 420-mg silymarin , and 3.8 % [ 95 % CI , 0.5 % to 13.2 % ] for 700-mg silymarin ) . The mean decline in serum ALT activity at the end of treatment did not differ significantly ( P = .75 ) across the 3 treatment groups ( mean decline , -4.3 [ 95 % CI , -17.3 to 8.7 ] U/L for placebo , -14.4 [ 95 % CI , -41.6 to 12.7 ] U/L for 420-mg silymarin , -11.3 [ 95 % CI , -27.9 to 5.4 ] U/L for 700-mg silymarin ) ; there likewise were no significant differences in HCV RNA levels ( mean change , 0.07 [ 95 % CI , -0.05 to 0.18 ] log10 IU/mL for placebo , -0.03 [ 95 % CI , -0.18 to 0.12 ] log10 IU/mL for 420-mg silymarin , 0.04 [ 95 % CI , -0.08 to 0.16 ] log10 IU/mL for 700-mg silymarin ; P = .54 ) or quality -of-life measures . The adverse event profile of silymarin was comparable with that of placebo . CONCLUSION Higher than customary doses of silymarin did not significantly reduce serum ALT levels more than placebo in participants with chronic HCV infection unsuccessfully treated with interferon-based therapy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00680342 BACKGROUND No pharmacologic agents have been approved for the treatment of non-alcoholic steatohepatitis ( NASH ) that is common in our region . The present study was design ed to evaluate the efficacy of silymarin , a known herbal drug , in the treatment of NASH . METHODS This clinical -trial study was conducted on 64 patients with NASH who were r and omly divided as case group ( 33 ) and control group ( 31 ) . Abdominal sonography and persistent elevation in levels of aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) more than 1.2 times of the upper normal limit within the last six months were selected as inclusion criteria . They were advised to take low-fat , low carbohydrate diet , do regular sport activity to lose weight up to 4 Kg . Patients in the case group received 210 mg/day silymarin orally for 8 weeks and those in the control group received placebo . After 8 weeks , the patients were reevaluated and their AST and ALT levels were measured . This study was registered in the Iranian Registry of Clinical Trial ( www.i rct .ir ) with registration number ID : I RCT 201202159018N1 . RESULTS The mean age of patients in case and control groups was 43.6±8.3 and 39.4±10.5 years , respectively . Their BMI were 27.4±1.7 and 27.5±1.9 , respectively . Their weights were also 79±9.2 and 76.9±9.5 kg , respectively . Serum concentrations of ALT were 91.3±21.3 and 38.4±11.8 in case group before and after the study respectively , whiles the figures were 84.6±23.3 and 52.3±29 in the control group ( P=0.026 ) . The same trend was seen for AST ( P=0.038 ) . CONCLUSION The patients who had taken silymarin experienced more notable fall in hepatic enzymes The only currently recommended treatment for nonalcoholic fatty liver disease ( NAFLD ) is lifestyle modification . Preliminary studies of silybin showed beneficial effects on liver function .  Realsil ( RA ) comprises the silybin phytosome complex ( silybin plus phosphatidylcholine ) coformulated with vitamin E. We report on a multicenter , phase III , double-blind clinical trial to assess RA in patients with histologically documented NAFLD . Patients were r and omized 1:1 to RA or placebo ( P ) orally twice daily for 12 months . Prespecified primary outcomes were improvement over time in clinical condition , normalization of liver enzyme plasma levels , and improvement of ultrasonographic liver steatosis , homeostatic model assessment ( HOMA ) , and quality of life . Secondary outcomes were improvement in liver histologic score and /or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines , ferritin , and liver fibrosis markers .  We treated 179 patients with NAFLD ; 36 were also HCV positive . Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol ( 69 per group ) . Baseline patient characteristics were generally well balanced between groups , except for steatosis , portal infiltration , and fibrosis . Adverse events ( AEs ) were generally transient and included diarrhea , dysgeusia , and pruritus ; no serious AEs were recorded . Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels , HOMA , and liver histology . Body mass index normalized in 15 % of RA patients ( 2.1 % with P ) . HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers . This is the first study to systematic ally assess silybin in NAFLD patients . Treatment with RA but not P for 12 months was associated with improvement in liver enzymes , insulin resistance , and liver histology , without increases in body weight . These findings warrant further investigation BACKGROUND / AIMS The incidence of obese patients with fatty liver has recently increased in Japan as well as in the United States and Europe . Fatty liver may occasionally progress to liver cirrhosis . In this study , we have compared the effects of restricted diet and exercise versus no treatment in obese patients with fatty liver . METHODS Twenty-five obese patients with fatty liver were divided into treated and control groups . Fifteen obese patients followed a program of restricted diet ( ideal weight x 25 Cal x kg(-1 ) ) and exercise ( walking or jogging ) for a trial period of 3 months . No changes in diet or lifestyle were made by the other 10 patients during the same trial period . Blood biochemical tests and liver histology were compared in all patients before and after the trial . RESULTS In the treated group , weight , blood biochemical data such as aminotransferase , albumin , cholinesterase , total cholesterol and fasting blood glucose values , and steatosis were significantly decreased after the trial . In the control group , there were no significant differences in the clinical and histological findings before and after the trial . CONCLUSIONS These results indicate that restricted diet and exercise therapy , such as walking and jogging , are useful means of improving blood biochemical data and histological findings in liver tissues related to fatty liver BACKGROUND / AIMS Silymarin has protective effects in different experimental conditions , but its efficacy in human liver cirrhosis has not been completely established . Therefore , this study was carried out to determine the effect of silymarin in alcoholics with liver cirrhosis with respect to survival and clinical and laboratory changes . METHODS From February 1986 to June 1989 , we enrolled 200 alcoholics with histologically or laparoscopically proven liver cirrhosis in a r and omized , double-blind multicenter trial comparing 450 mg of silymarin ( 150 mg/ three times per day ) with placebo . The primary outcome was time to death , and the secondary outcome was the progression of liver failure . Additional analyses were also performed in 75 patients in whom anti-hepatitis C virus antibodies were measured after completion of the trial . RESULTS One hundred and three patients were assigned to receive silymarin  and 97 to receive placebo . The two groups were well matched for demographic and baseline clinical and laboratory features . A 2-year study period was completed in 125 patients ( 57 receiving silymarin and 68 receiving placebo )  . Twenty-nine patients ( 15 receiving silymarin , and 14 receiving placebo ) died during the trial . Survival was similar in patients receiving silymarin or placebo . The effect of silymarin on survival was not influenced by sex , the persistence of alcohol intake , the severity of liver dysfunction or by the presence of alcoholic hepatitis in the liver biopsy . Silymarin did not have any significant effect on the course of the disease . No relevant side-effects were observed in any group . CONCLUSIONS The results of this study indicate that silymarin has no effect on survival and the clinical course in alcoholics with liver cirrhosis BACKGROUND / AIMS Several studies have demonstrated that diabetic patients with cirrhosis require insulin treatment because of insulin resistance . As chronic alcoholic liver damage is partly due to the lipoperoxidation of hepatic cell membranes , anti-oxidizing agents may be useful in treating or preventing damage due to free radicals . The aim of this study was to ascertain whether long-term treatment with silymarin is effective in reducing lipoperoxidation and insulin resistance in diabetic patients with cirrhosis . METHODS A 12-month open , controlled study was conducted in two well-matched groups of insulin-treated diabetics with alcoholic cirrhosis . One group ( n=30 ) received 600 mg silymarin per day plus st and ard therapy , while the control group ( n=30 ) received st and ard therapy alone . The efficacy parameters , measured regularly during the study , included fasting blood glucose levels , mean daily blood glucose levels , daily glucosuria levels , glycosylated hemoglobin ( HbA1c ) and malondialdehyde levels . RESULTS There was a significant decrease ( p<0.01 ) in fasting blood glucose levels , mean daily blood glucose levels , daily glucosuria and HbA1c levels already after 4 months of treatment in the silymarin group . In addition , there was a significant decrease ( p<0.01 ) in fasting insulin levels and mean exogenous insulin requirements in the treated group , while the untreated group showed a significant increase ( p<0.05 ) in fasting insulin levels and a stabilized insulin need . These findings are consistent with the significant decrease ( p<0.01 ) in basal and glucagon-stimulated C-peptide levels in the treated group and the significant increase in both parameters in the control group . Another interesting finding was the significant decrease ( p<0.01 ) in malondialdehyde/levels observed in the treated group . CONCLUSIONS These results show that treatment with silymarin may reduce the lipoperoxidation of cell membranes and insulin resistance , significantly decreasing endogenous insulin overproduction and the need for exogenous insulin administration BACKGROUND / AIMS Silybum marianum is a herbal preparation commonly used by subjects with chronic hepatitis C ( CHC ) . The aims of this pilot study were to assess the efficacy and safety of S. marianum on serum hepatitis C virus ( HCV ) RNA , alanine aminotransferase levels and well-being in patients with CHC . METHODS Twenty-four subjects with CHC were enrolled into a r and omized , double-blind , placebo-controlled , crossover study . Subjects received 12 weeks of S. marianum ( either 600 mg or 1200 mg/day ) and placebo separated by a 4-week washout interval . Baseline biochemical , virological , psychological and quality -of-life tests were performed , with biochemical tests repeated monthly , and HCV RNA titer and quality -of-life and psychological assessment s repeated at the end of both treatment periods . RESULTS Seventeen patients completed the trial .  Mean changes in HCV RNA titers , serum ALT levels and Short Form-36 scores were not significantly different for subjects on S. marianum compared to those on placebo . There was no significant change in mean State-Trait Anxiety Inventory State-Anxiety scores on S. marianum from baseline . Adverse events were similar with S. marianum and placebo . CONCLUSIONS S. marianum is well tolerated in subjects with CHC , but does significantly affect serum HCV RNA , alanine aminotransferase levels , quality of life or psychological well-being in subjects with this condition The Romanian product Silimarina ( synonym Legalon ) was administered in a r and omized double-blind trial , to a group of 180 patients with chronic persistent hepatitis ( CPH ) , chronic active hepatitis ( CAH ) and hepatic cirrhosis ( HC ) . The trial lasted for 40 days . The results showed favourable effects similar with those obtained with other preparations produced by foreign drug industries . The Romanian product proved to have no toxic effect . The authors discuss the present possibilities of estimating the evolution of chronic liver disease BACKGROUND / AIMS A double-blinded trial evaluating silymarin , an herbal supplement for liver disease , to prevent complications of chronic hepatitis C virus infection has not been done . SUBJECTS One hundred and seventy-seven consenting residents of an Egyptian village with chronic hepatitis C virus were r and omly assigned to receive either silymarin or multivitamin supplements . METHODS Participants had baseline and follow-up clinical , ultrasound , blood tests and quality -of-life assessment s. Community nurses visited weekly to ascertain compliance , distribute supplements and record adverse effects . RESULTS At 12 months almost all of 141 remaining subjects reported feeling better , although symptoms and quality -of-life scores did not differ between the silymarin and multivitamin groups . Both the silymarin and vitamins were tolerated equally well ; and > 95 % of supplements were taken by > 95 % of subjects . One in each group had no detectable hepatitis C virus antibodies while two in the silymarin group and three receiving multivitamins had undetectable hepatitis C virus RNA . Serum alanine aminotransferase elevations did not differ between groups . Serum hepatic fibrosis marker , hyaluronic acid and YKL-40 , and abdominal ultrasound results were similar in both groups and may have progressed slightly at 12 months . CONCLUSIONS The recommended dose of silymarin can be safely taken for 1 year and improves symptoms and general well-being , but has no effect upon hepatitis C virus viremia , serum ALT , or serum and ultrasound markers for hepatic fibrosis . More prolonged evaluation and a higher dose may be required to ascertain whether milk thistle supplements prevent complications of chronic hepatitis C virus BACKGROUND : Silymarin derived from silybum marianum ( milk thistle ) , a flowering member of the daisy family , may benefit liver function in people infected with the hepatitis C virus . The aims of this pilot study were to assess the efficacy and safety of silymarin on serum hepatitis C virus ( HCV ) RNA , serum aminotransferases ( ALT , AST ) levels , liver fibrosis and well-being in patients with chronic hepatitis C ( CHC ) . METHODS : This prospect i ve self-controlled trial study was conducted from March to September 2006 at Department of Gastroenterology , Isfahan University of Medical Sciences , Isfahan , Iran . 55 patients with HCV ( 10 female and 45 male ) with a mean age of 31.8 ± 6.4 years ( 10 - 67 years ) were participated in the study . Patients received 24 weeks of silymarin ( 630 mg/day ) . Baseline virological biochemical , liver fibrosis ( by a serum fibrosis markers , including YKL–40 and Hyaluronic acid ) , and SF-36 question naire were performed with biochemical tests repeated at the end of the treatment period . RESULTS : There was statistically difference in mean of ALT ( 108.7 ± 86.6 vs 70.3 ± 57.7 ) before and after the treatment ( p < 0.001 ) . The means of AST were 99.4 ± 139.7 and 59.7 ± 64.32 before and after the treatment with statistically differences ( p = 0.004 ) . After the treatment , nine patients were found with negative HCV-RNA ( p = 0.004 ) and statistically significant improvement in results of liver fibrosis markers were found only in fibrosis group ( p = 0.015 ) . Quality of life was improved significantly ( p < 0.001 ) . CONCLUSIONS : This study indicated that in patients with CHC  performing silymarin ( 650 mg/day ) for 6 months , improved serum HCV-RNA titer , serum aminotransferases ( ALT , AST ) , hepatic fibrosis and patient 's quality of life . More future studies are warranted PURPOSE Milk thistle or its purified extract , silymarin ( Silybum marianum ) , is widely used in treating acute or chronic hepatitis . Although silymarin is hepatoprotective in animal experiments and some human hepatotoxic exposures , its efficacy in ameliorating the symptoms of acute clinical hepatitis remains inconclusive . In this study , our purpose was to determine whether silymarin improves symptoms , signs and laboratory test results in patients with acute clinical hepatitis , regardless of etiology . METHODS This is a r and omized , placebo-controlled trial in which participants , treating physicians and data management staff were blinded to treatment group . The study was conducted at two fever hospitals in Tanta and Banha , Egypt where patients with symptoms compatible with acute clinical hepatitis and serum alanine aminotransferase ( ALT ) levels > 2.5 times the upper limit of normal were enrolled . The intervention consisted of three times daily ingestion of either a st and ard recommended dose of 140 mg of silymarin ( Legalon , MADAUS GmbH , Cologne , Germany ) , or a vitamin placebo for four weeks with an additional four-week follow-up . The primary outcomes were symptoms and signs of acute hepatitis and results of liver function tests on days 2 , 4 and 7 and weeks 2 , 4 , and 8 . Side-effects and adverse events were ascertained by self-report . RESULTS From July 2003 through October 2005 , 105 eligible patients were enrolled after providing informed consent . No adverse events were noted and both silymarin and placebo were well tolerated . Patients r and omized to the silymarin group had quicker resolution of symptoms related to biliary retention : dark urine ( p=0.013 ) , jaundice ( p=0.02 ) and scleral icterus ( p=0.043 ) . There was a reduction in indirect bilirubin among those assigned to silymarin ( p=0.012 ) , but other variables including direct bilirubin , ALT and aspartate aminotransferase ( AST ) were not significantly reduced . CONCLUSIONS Patients receiving silymarin had earlier improvement in subjective and clinical markers of biliary excretion . Despite a modest sample size and multiple etiologies for acute clinical hepatitis , our results suggest that st and ard recommended doses of silymarin are safe and may be potentially effective in improving symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process Background : Non-alcoholic fatty liver disease is the most common liver disease worldwide . Aim : The aim of this study is to compare the metabolic effects of the Mediterranean diet versus the diet associated with silybin , phosphatidylcholine and vitamin E complex in overweight patients with non-alcoholic fatty liver disease . Methods : Thirty Caucasian overweight patients were r and omized into three groups of 10 ( Groups A , B and C ) . A personalized Mediterranean diet was started in Group A and B patients . In association with the diet , Group B patients were given Realsil complex , daily , for 6 months . Group C patients refused any treatment . Results : We showed that the Mediterranean diet alone , or in association with the Realsil complex , led to the significant variation in BMI , waist circumference , total cholesterol and triglycerides . We also observed a statistically significant decrease in homeostasis model assessment technique in Group B patients The study was undertaken to determine the long-term effect of misoprostol , on  hepatitis B virus ( HBV ) elimination  in patients treated during acute phase of viral hepatitis B. Forty male patients were evaluated 12 months after treatment with misoprostol ( M-group ) or sylimarin ( S-group ) .  HBsAg clearance , as an indicator of HBV elimination , and serum bilirubin concentration , prothrombin index , and activities of alanine transaminase , aspartate transaminase , alkaline phosphatase as well as gamma glutamyltranspeptidase were analysed . At the end of treatment phase , improvement of liver function demonstrated through these biochemical indices was faster in M-group . After 12 months of follow-up HBsAg was cleared in all misoprostol treated patients and in 85 % among S-group . Moreover misoprostol treatment result ed with normalization of bilirubin concentration and enzymes activity in all patients . Two among sylimarin treated patients ( both HBsAg positive ) , had transaminases activities elevated over 100 U/l , that result ed with significantly higher values than in M-group . These results confirm beneficial effect of misoprostol treatment in patients with liver injury , but promising effect on HBV clearance should be confirmed in a study involving more patients Goals The goal of this study was to examine the effect of a st and ardized silybin and soy phosphatidylcholine complex ( IdB 1016 ) on serum markers of iron status . Background Milk thistle and its components are widely used as an alternative therapy for liver disease because of purported antioxidant , anti-inflammatory , and iron chelating properties . Study Thirty-seven patients with chronic hepatitis C and Batts-Ludwig fibrosis stage II , III , or IV were r and omized to 1 of 3 doses of IdB 1016 for 12 weeks . Serum ferritin , serum iron , total iron binding capacity , and transferrin-iron saturation were measured at baseline , during treatment , and 4 weeks thereafter . Wilcoxon signed rank tests were used to compare baseline and posttreatment values . Results There was a significant decrease in serum ferritin from baseline to end of treatment ( mean , 244 vs. 215 μg/L ; median , 178 vs. 148 μg/L ; P=0.0005 ) ; 78 % of subjects had a decrease in serum ferritin level . There was no significant change in serum iron or transferrin-iron saturation . Multivariate logistic regression analysis in a model that included dose , age , sex , HFE genotype , history of alcohol use , and elevated baseline ferritin levels demonstrated that stage III or IV fibrosis was independently associated with decreased posttreatment serum ferritin level . Conclusions Treatment with IdB 1016 is associated with reduced body iron stores , especially among patients with advanced fibrosis stage Although nonalcoholic steatohepatitis ( NASH ) has generally been considered a benign condition , the increasing prevalence and severity of obesity has heightened concerns about the frequency with which NASH progresses to end-stage liver disease . The aim of this study is to determine the frequency , clinical features , and posttransplantation history of decompensated liver disease secondary to NASH . The frequency of NASH as a cause of end-stage liver disease was prospect ively determined in patients evaluated for liver transplantation . NASH was considered to be the primary cause of liver disease in patients who had histological evidence of steatohepatitis and in whom chronic liver diseases other than NASH were excluded .  Posttransplantation histological characteristics were also determined in patients with NASH and compared with those of patients with pretransplantation diagnoses of cholestatic liver diseases , alcoholic disease , and hepatitis C. Of 1,207 patients evaluated for liver transplantation during the study period , 31 patients ( 2.6 % ) had NASH as the primary cause of liver disease . In the same period , 546 liver transplantations were performed , 16 of which ( 2.9 % ) were for end-stage disease secondary to NASH . Posttransplantation steatosis was seen in 60 % of transplant recipients with NASH versus 5 % of those with cholestatic disease , 15 % of those with alcoholic disease , and 15 % of those with hepatitis C. Steatohepatitis recurred in 33 % of transplant recipients with NASH , with progression to cirrhosis in 12.5 % . NASH can progress to end-stage liver disease in a minority of affected patients and was the primary cause of liver disease in 2.9 % of patients evaluated for liver transplantation at our center . Recurrence of steatosis and NASH is frequent and can be severe after liver transplantation
target: There was no significant change in the γGT levels .
  Significant differences were not found .
  CONCLUSION Silymarin minimally reduced , but without clinical relevance , the serum levels of ALT and AST .
background: AIM To evaluate the effect of silymarin on the serum levels of alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) and gamma glutamyl transpeptidase ( γGT ) in patients with liver diseases .