title: High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial. Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. Interim analysis of a double-blind multicentre randomized trial. The UDCA-PBC Study Group. Ursodeoxycholic acid for symptomatic primary biliary cirrhosis. Preliminary analysis of a double-blind multicenter trial. Italian Multicenter Group for the Study of UDCA in PBC. Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on nonalcoholic fatty liver disease: double-blind, randomized clinical trial of efficacy and safety Weight reduction and ursodeoxycholic acid in subjects with nonalcoholic fatty liver disease. A double-blind, placebo-controlled trial. Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver. DISSOLUTION OF CHOLESTEROL GALLSTONES BY URSODEOXYCHOLIC ACID Serum cholestanol, cholesterol precursors, and plant sterols during placebo-controlled treatment of primary biliary cirrhosis with ursodeoxycholic acid or colchicine. Effect of ursodeoxycholic acid on serum lipids of patients with primary biliary cirrhosis. A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid. Chenodeoxycholic acid and ursodeoxycholic acid effects in endogenous hypertriglyceridemias. A controlled double-blind trial. Effect of high and low doses of ursodeoxycholic acid on gallstone dissolution in humans. Comparative efficacy and side effects of ursodeoxycholic and chenodeoxycholic acids in dissolving gallstones. A double-blind controlled study. Serum plant sterols and biliary cholesterol secretion in humans: studies with ursodeoxycholic acid. Cholesterol-lowering effect of ursodeoxycholic acid in patients with primary biliary cirrhosis. NUtraceutical TReatment for hYpercholesterolemia in HIV-infected patients: The NU-TRY(HIV) randomized cross-over trial.
abstract: UNLABELLED In uncontrolled clinical studies , ursodeoxycholic acid ( UDCA ) had a beneficial effect on  nonalcoholic steatohepatitis ( NASH ) .  However , a large controlled trial using UDCA ( 13 - 15 mg/kg/day ) was unable to confirm these results . Accordingly , a r and omized , placebo-controlled study was initiated with a high dose of UDCA ( 23 - 28 mg/kg/day ) . The allocation of patients and the evaluation of liver histology were performed according to a modified Brunt score and the nonalcoholic fatty liver disease activity score ( NAS ) . With the modified Brunt score , 185 patients with histologically proven NASH were r and omized [ intention to treat ( ITT ) ] , and 147 were treated per protocol ( PP ) . With the NAS , 137 patients were confirmed to have NASH , 48 had borderline NASH , and 1 did not have NASH . The treatment time was 18 months . At entry , the treatment groups were comparable . A second biopsy sample was obtained from 139 of 185 patients ( NAS : 107/137 ) . The primary criterion for evaluation was a change in the liver histology ; the secondary criteria were single histological variables and liver biochemistry . Significant differences in the overall histology could not be detected between the two treatment groups with the modified Brunt score ( P = 0.881 ) or NAS ( P = 0.355 ) . Only lobular inflammation improved significantly ( P for the modified Brunt score = 0.011 , P for NAS = 0.005 ) . In subgroup analyses , significant improvements in lobular inflammation were also observed in males , younger patients up to 50 years of age , slightly overweight patients , and patients with hypertension and an increased histology score . The fibrosis score did not change ( P for ITT = 0.133 , P for PP = 0.140 ) . With the exception of gamma-glutamyl transferase , UDCA did not improve laboratory data . CONCLUSION High-dose UDCA failed to improve the overall histology in patients with NASH in comparison with placebo Based on uncontrolled observations , we have proposed ursodeoxycholic acid ( UDCA ) as a novel therapeutic approach in primary biliary cirrhosis ( PBC ) . To confirm and extend our original findings , we have design ed a double-blind multicentre r and omized clinical trial . An interim analysis was planned at 6 months , involving all subjects included in the trial , with a final analysis at 2 years . The  UDCA-PBC trial began in June 1987 and will be completed in March 1990 . Seventy patients were r and omized to receive UDCA and 68 a placebo .  The two groups were well matched with respect to age , sex , duration and prevalence of symptoms and histologic severity ( 50 % of the UDCA group had stage III-IV disease vs. 37 % of the placebo group ) . During the first 6 months of follow-up , six patients withdrew from the trial . At 6 months , the proportion of patients with jaundice was significantly lower ( p less than 0.01 ) in UDCA recipients than in the placebo group . There was a similar decrease in the proportion of patients with pruritus and fatigue in both groups . The following laboratory test values were significantly lower in UDCA recipients than in the placebo group after 6 months of therapy : serum bilirubin , alkaline phosphatase , alanine aminotransferase ( ALAT ) , aspartate aminotransferase ( ASAT ) , gamma-glutamyltranspeptidase activities ( p less than 0.001 ) , cholesterol ( p less than 0.003 ) and IgM levels ( p less than 0.03 ) . The results of this interim analysis confirm and extend the biochemical data provided by our previous pilot study . However the final analysis of the trial is necessary for a definitive assessment of the safety and efficacy of UDCA therapy in PBC The administration of ursodeoxycholic acid , a hydrophilic bile acid not hepatotoxic to humans , has been suggested for treatment of primary biliary cirrhosis to improve cholestasis and reduce hepatocellular damage . Efficacy of treatment has been studied mainly in patients with asymptomatic or early-stage disease . In January 1988 , to establish the efficacy and safety of ursodeoxycholic acid in a population with more severe disease , we started a multicenter , double-blind , placebo-controlled trial in patients with symptomatic disease , that is , with pruritus or serum bilirubin exceeding 2 mg/dl . Forty-four patients were assigned to ursodeoxycholic acid , 500 mg daily ( corresponding to about 8.7 mg/kg body weight in these patients ) , and 44 to a placebo . As planned at the beginning of the study , a preliminary analysis was performed when all patients had been followed for at least 6 months ( 33 patients up to 12 months ) . Pruritus , self-evaluated by the patients , and cholestyramine consumption , as recorded in a diary , decreased significantly ( p < 0.01 ) in both groups . In patients who initially had abnormal levels , serum bilirubin decreased significantly ( p < 0.05 ) in the ursodeoxycholic acid group compared to placebo . After 6 months the following were also significantly better in the ursodeoxycholic acid than in the placebo group : a composite weighted biochemical index taking into account the changes in serum bilirubin , alkaline phosphatase , gamma-GT and AST ( p < 0.001 ) ; serum prealbumin ( p < 0.05 ) ; IgG ( p < 0.01 ) and IgM ( p < 0.01 ) levels . ( ABSTRACT TRUNCATED AT 250 WORDS Background and purpose Nonalcoholic fatty liver disease ( NAFLD ) is one of the causes of a fatty liver , occurring when fat is deposited ( steatosis ) in the liver not due to excessive alcohol use . It is related to insulin resistance and the metabolic syndrome . The purpose of the present study was to evaluate the impact of combination therapy with alpha-lipoic acid ( ALA ) and ursodeoxycholic acid ( UDCA ) on NAFLD . Methods Alpha-lipoic acid 400 mg/day plus UDCA 300 mg/day ( ALAUDCA ) was investigated in patients over a period of 12 months using a r and omized , placebo (PLA)-controlled study with four parallel groups . Serum concentration of gamma-glutamyl transpeptidase ( GGT ) , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , albumin and platelets ( PLT ) were measured at the beginning and at the end of the treatment . Moreover , the AST/ALT ratio and the NAFLD fibrosis score were examined . Results A total of 120 patients were r and omly assigned to the four groups . ALA and UDCA were safe and well tolerated in the oral daily administration only . AST , ALT , GGT ( p < 0.001 ) showed a significant difference between ALAUDCA and other three groups . Besides , NAFLD fibrosis score underlined a significant reduction ( p < 0.04 ) in the ALAUDCA group , while AST/ALT ratio presented a moderate decline ( p > 0.05 ) . Conclusion ALAUDCA therapy reduced AST , ALT , GGT values and improved NAFLD fibrosis score and AST/ALT ratio , especially in patients who were on a hypocaloric diet . These findings will be useful in patient selection in future clinical trials with ALAUDCA in long-term studies OBJECTIVE Nonalcoholic fatty liver disease is an increasingly recognized condition that may progress to end-stage liver disease . We investigated the effects of weight reduction and ursodeoxycholic acid administration in patients with this disease . RESEARCH METHODS AND PROCEDURES A double-blind , placebo-controlled trial . Twenty-seven women with a body mass index of > 30 kg/m2 and willing to participate in the diet plan for six weeks were studied were assigned to one of two treatment groups ( ursodeoxycholic acid , n = 14 : placebo n = 13 ) . Both groups received a normal diet ( 1,200 kcal/d ) plus 1200 mg/d of ursodeoxycholic acid or placebo .  Hepatic steatosis , was assessed by abdominal ultrasound . Fasting glucose , cholesterol , triglycerides , and aminotransferases levels were determined before and after treatment . RESULTS Body mass index decreases significantly from 34.2 + /- 4.2 kg/m2 and 33.3 + /- 1.6 kg/m2 to 31.8 + /- 4.5 kg/m2 and 30.6 + /- 2.6 kg/m2 in the ursodeoxycholic acid and placebo groups , p < 0.001 . The hepatic steatosis index decreased from 2.3 + /- 0.7 to 1.0 + /- 0.6 and 2.2 + /- 0.7 to 1.1 + /- 0.7 in the ursodeoxycholic acid and placebo groups , p<0.003 . Serum AST decreased significantly from 41.2 + /- 5.6 to 34.5 + /- 3.4 in the ursodeoxycholic acid group , p < 0.001 , and from 43.6 + /- 4.2 to 35.3 + /- 2.9 in the placebo group , p < 0.001 . Serum ALT decreased from 62.9 + /- 6.5 to 44.0 + /- 3.5 in the ursodeoxycholic acid group , p < 0.001 , and from 63.5 + /- 4.5 to 44.0 + /- 3.5 in the placebo group . We did not find any differences in all variables studied between groups . CONCLUSIONS The present study shows beneficial effect of weight reduction , producing improvements in biochemical and imaging markers of liver disease BACKGROUND / AIM The aim of this study was to assess the efficacy of ursodeoxycholic acid ( UDCA ) for primary biliary cirrhosis in a r and omized , double-blind placebo-controlled trial . METHODS Consecutive patients ( n=192 ) were r and omized to receive 14 - 16 mg UDCA/kg/day or placebo .  Patients underwent a complete history , physical examination , liver chemistries , immunological determinations and liver biopsy at entry and at the end of the trial , which lasted for at least 2 years . Patients were seen every 3 months and the median follow-up was 3.4 years ( range 0.3 to 6.1 years ) . RESULTS Patients receiving UDCA ( 99 ) or placebo ( 93 ) were comparable with regard to age , sex , biochemical parameters and liver histology . UDCA treatment was associated with decreases in alkaline phosphatase , gammaglutamyl transferase , alanine aminotransferase , and cholesterol levels , effects which were conspicuous after 3 months of treatment and remained similar during the follow-up . During the study 31 patients ( 10 receiving UDCA and 21 placebo ) discontinued the trial because of noncompliance ( n=11 ) , voluntary withdrawal ( n=19 ) or adverse effects ( n=1 ) .  Treatment failure ( death or liver transplantation ) was observed in 17 patients receiving UDCA and in 11 patients receiving placebo . Times to death or liver transplantation and to clinical complications were not significantly different in patients receiving UDCA or placebo . Histological analysis indicates that UDCA improved portal inflammation and prevented histological stage progression . By contrast , histological stage as well as ductular proliferation and ductopenia progressed in patients receiving placebo . CONCLUSIONS Although UDCA treatment did not significantly affect time to death or liver transplantation and to clinical complications , the effects on both cholestasis and liver histology suggest that UDCA is safe and may be useful for preventing the progression of primary biliary cirrhosis 44 patients with radiolucent gallstones in gallbladders visible on cholecystography were r and omly alloted to three treatment groups : ursodeoxycholic acid ( 600 mg/day ) , ursodeoxycholic acid ( 150 mg/day ) , a placebo . At the end of six months ' treatment , cholecystograms of all the patients were interpreted by radiologists who were not aware of the treatment . Dissolution of gallstones occurred in 8 ( 26 % ) of the 31 patients treated with ursodeoxycholic acid , but not in the placebo group . Ursodeoxycholic acid had no hepatotoxicity , as assessed by st and ard liver-function tests . These results indicate that ursodeoxycholic acid , the 7beta epimer of chenodeoxycholic acid , is effective in the dissolution of cholesterol gallstones A r and omized placebo-controlled 2-year study was performed in 69 patients with primary biliary cirrhosis ( PBC ) on serum lipids during ursodeoxycholic acid ( URSO ) and colchicine treatments .  In addition to serum bilirubin and alkaline phosphatase ( AFOS ) , two variables considered to reflect liver function , serum lipoproteins , cholesterol precursors ( squalene , delta 8-cholestenol , lathosterol and desmosterol ) , markers of cholesterol synthesis , cholestanol and plant sterols ( campesterol and sitosterol ) , markers of liver function and cholesterol absorption , were studied before and during the treatments . Serum bilirubin was inconsistently improved by URSO , whereas improvement of AFOS values was better by URSO than colchicine , especially in patients with initially more advanced PBC . Serum total cholesterol was reduced by both drugs , very low-density lipoprotein ( VLDL ) and high-density lipoprotein ( HDL ) cholesterol by URSO .  Cholesterol precursor sterols were increased by both URSO and colchicine mainly in patients with initially less severe PBC . On the other h and , the cholestanol values were markedly increased initially , and the values were related to bilirubin during the 2-year period , were further increased in the placebo group , and reduced in the URSO and colchicine groups , so that the improvement was highest in the URSO-treated patients with the severe form of PBC . The increase of the serum plant sterols , particularly that of sitosterol , was retarded by the two drugs so that the campesterol/sitosterol ratio , which was related to serum bilirubin , was increased especially in the cases with initially more advanced PBC . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To study the effects of ursodeoxycholic acid ( UDCA ) on lipid levels in patients with primary biliary cirrhosis ( PBC ) . DESIGN A r and omized , placebo-controlled prospect i ve trial of UDCA was conducted in 177 well-characterized patients with PBC . MATERIAL AND METHODS The two treatment groups ( placebo and UDCA ) were matched at entry with respect to age , sex , histologic stage of PBC , biochemical values , and serum lipid levels . Serum cholesterol , high-density lipoprotein cholesterol , and triglyceride levels were measured at entry , 1 year , and 2 years . RESULTS The decrease in total cholesterol level at 1 and 2 years in the UDCA-treated group was significant in comparison with that in the placebo group . Serum high-density lipoprotein cholesterol and triglyceride levels , however , were unchanged . No severe side effects from UDCA were noted . The changes in serum cholesterol levels at 2 years were directly and strongly correlated with changes in serum bilirubin concentrations ( r = 0.70 ; P < 0.001 ) and inversely correlated with initial serum cholesterol levels ( r = -0.86 ; P < 0.00001 ) . CONCLUSION The cholesterol-lowering effect of UDCA could be related to amelioration of the underlying liver disease or to a direct effect of the drug on the metabolism of cholesterol in patients with hypercholesterolemia BACKGROUND / AIMS Ursodeoxycholic acid ( UDCA ) and colchicine have beneficial effects in primary biliary cirrhosis ( PBC ) . The efficacy of colchicine and UDCA in PBC was compared in a 2-year  placebo-controlled study ( n = 90 ) . METHODS Clinical events , laboratory test results , and liver histology were recorded at the beginning and end of the trial . RESULTS There were significantly fewer dropouts for hepatic reasons with UDCA than with placebo .  Pruritus was reduced by both active drugs . Colchicine improved liver function test results only modestly , whereas UDCA significantly decreased the serum activities of aminotransferases , alkaline phosphatase , and gamma-glutamyltransferase compared with colchicine and placebo .  Serum total bilirubin levels were decreased only by UDCA . Both colchicine and UDCA reduced serum cholesterol levels , and UDCA also reduced high-density lipoprotein cholesterol levels . Furthermore , UDCA reduced the serum levels of immunoglobulin ( Ig ) M and IgG , and colchicine reduced IgG levels compared with placebo . The elevated serum level of aminoterminal propeptide of type III procollagen remained unchanged by colchicine or UDCA , whereas the serum level of carboxyterminal propeptide of type I procollagen was significantly decreased by UDCA . UDCA significantly decreased ductular proliferation compared with colchicine or placebo . CONCLUSIONS These data suggest that UDCA frequently is superior to colchicine and especially to placebo in the treatment of PBC A double-blind controlled trial was carried out to compare the effects of chenodeoxycholic acid ( CDCA ) , ursodeoxycholic acid ( UDCA ) , and placebo on cholesterol and triglyceride levels in patients with endogenous hypertriglyceridemias . The dose of both bile acids was four 150-mg capsules day . Total serum cholesterol levels did not show appreciable changes with any of the treatments . HDL cholesterol was significantly increased after CDCA but not after UDCA or placebo . CDCA feeding was associated with a significant decrease in serum triglyceride levels , whereas the other treatments failed to show an effect . It is concluded that UDCA does not affect serum lipid levels , whereas CDCA lowers serum triglycerides and may be useful in the treatment of endogenous hypertriglyceridemia To test the effectiveness of ursodeoxycholic acid as a gallstone dissolving agent , doses of 250 mg/day and 1000 mg/day were administered for 1 year to two groups of 10 and 11 subjects each . Success was defined as a reduction in stone size and number of 50 % or more . Both groups of subjects were similar when comparing age , height , weight , gallstone size , and number although more men were enrolled in the high-dose treatment group . After 1 yr of high-dose ursodeoxycholic acid , successful treatment occurred in 70 % of subjects associated with a rise in biliary ursodeoxycholic acid  ( 1.7 to 51 % ) and a decline in the proportions of cholic acid ( 36 to 16 % ) , deoxycholic acid ( 19 to 10 % ) , chenodeoxycholic acid ( 41 to 23 % ) , and lithocholic acid ( 1.9 to 0.4 % ) . The mean cholesterol saturation index decreased from 1.5 to 0.7 and was accompanied by a 3.0-fold reduction in the activity of HMG CoA reductase ( 81 to 29 units ) in 2 subjects . With low-dose ursodeoxycholic acid , successful treatment occurred in 30 % of subjects accompanied by a rise in biliary ursodeoxycholic acid  to 29 % of total bile acids ; and a decline in deoxycholic acid ( 33 to 25 % ) , chenodeoxycholic acid ( 46 to 22 % ) , and lithocholic acid ( 4.0 to 2.4 % ) , while cholic acid ( 22 % ) did not change . The mean cholesterol saturation index fell from 1.9 to 1.2 . No untoward effects ( diarrhea or elevated serum transaminase levels ) were noted in either group . These results confirm that both high and low doses of ursodeoxycholic acid dissol ve gallstones in humans and were not associated with uncomfortable side effects . However , high doses of ursodeoxycholic acid were more effective and produced a greater reduction in the cholesterol saturation index , presumably by reducing hepatic cholesterol synthesis . Thus , the smallest effective dose of ursodeoxycholic acid probably lies between 250 mg and 1000 mg/day In a double-blind controlled study of ursodeoxycholic acid ( 400 and 800 mg/day ) and chenodeoxycholic acid ( 375 and 750 mg/day ) , in comparison with placebo , ursodeoxycholic acid was significantly more effective than chenodeoxycholic acid in dissolving gallstones after 12 mo of treatment . Although there continued to be better dissolution during ursodeoxycholic acid treatment ( dissolution complete in 30 % and partial in another 30 % of the patients ) than during chenodeoxycholic acid treatment ( dissolution complete in 7 % and partial in 40 % ) at 24 mo , this difference between the treatment groups was no longer statistically significant . The incidence of floating stones was significantly higher in the patients who dissolved their stones than in those who did not ( p less than 0.001 ) . The three failures of dissolution of floating stones during bile acid treatment were associated with chenodeoxycholic acid therapy -- two of them with the 750-mg and the third with the 375-mg doses . Gallstone dissolution with ursodeoxycholic acid occurred in spite of a rise in biliary cholesterol saturation , which was consistent with a nonmicellar mechanism of cholelitholysis . Furthermore , more than threefold serum elevations of L-alanine aminotransferase were observed only during chenodeoxycholic acid therapy . They occurred in 2 patients treated with 375 and 750 mg/day , respectively . The enzyme levels normalized after discontinuation of chenodeoxycholic acid and have remained normal for 13 and 8 mo , respectively , after the institution of treatment with 800 mg/day of ursodeoxycholic acid . There was no correlation between the liver tests and biliary levels of lithocholic acid . Of all the symptoms studied , only constipation showed changes that approached statistical significance ( p = 0.0681 ) . There was a significant improvement of constipation in the combined chenodeoxycholic acid groups when they were compared with the combined ursodeoxycholic acid groups . The total bile acid pool exp and ed significantly in both the chenodeoxycholic acid and in the 800-mg ursodeoxycholic acid treatment groups . The marked increases of biliary ursodeoxycholic acid and chenodeoxycholic acid  , respectively , indicated compliance with the treatment in all but 1 bile acid-treated patient . Neither serum triglycerides nor serum cholesterol showed significant changes in any of the treatment groups . The study shows that ursodeoxycholic acid  dissolves gallstones faster and with fewer side effects than chenodeoxycholic acid . The results of the study are also consistent with the view that ursodeoxycholic acid is cholelitholytic at a lower dose than is chenodeoxycholic acid Ratios of cholestanol , campesterol , and sitosterol to cholesterol in serum are known to reflect cholesterol absorption efficiency . Here , a possible link between these ratios and biliary secretion rates of cholesterol was investigated . Biliary lipid secretion rates and serum sterols were determined in 13 patients with gallstones . Seven were treated with ursodeoxycholic acid ( UDCA ) ( 1,000 mg/d ) . Serum cholesterol and non-cholesterol sterols were also measured in a cross over study in 20 healthy volunteers , who received either placebo or UDCA ( 750 mg/d ) .  Biliary cholesterol secretion was significantly lower , whereas the non-cholesterol sterols and their ratio to cholesterol were higher in patients with gallstones treated with UDCA .  A highly significant negative linear correlation between the ratios of non-cholesterol sterols to cholesterol and biliary cholesterol secretion was observed . In volunteers , administration of UDCA for 4 weeks was followed by a significant increase in non-cholesterol sterols and their ratios . Even 4 weeks after discontinuing UDCA administration , campesterol and sitosterol were still significantly higher than pretreatment levels , which was also true for the campesterol-cholesterol ratio after 8 weeks . The results suggest that the ratios of cholestanol , campesterol , and sitosterol to cholesterol can be used as indicators of changes in biliary cholesterol secretion rates We have previously shown in a 2-yr controlled trial that hypercholesterolemia , frequent in primary biliary cirrhosis , is lowered by ursodeoxycholic acid ( 13 to 15 mg daily ) . To further investigate this effect , we analyzed the influence of long-term ursodeoxycholic acid administration on serum lipids , lipoproteins and bile acids . The study involved a subgroup of 33 noncirrhotic patients ( 17 received ursodeoxycholic acid and 16 received a placebo ) analyzed at inclusion and after 2 yr . The total serum cholesterol concentration was markedly reduced in the  ursodeoxycholic acid-treated  patients in comparison with the controls ( mean + /- S.E.M. = 7.49 + /- 0.42 mmol/L and 7.07 + /- 0.23 mmol/L at entry and 4.44 + /- 0.40 mmol/L and 6.89 + /- 0.27 mmol/L at 2 yr in the ursodeoxycholic acid and placebo groups , respectively ; p < 0.02 ) . Quantitatively , this decrease was mainly caused by a fall in low-density-lipoprotein cholesterol , but very low density-lipoprotein cholesterol levels also fell significantly . High-density-lipoprotein cholesterol levels remained stable in both groups , but the high-density-lipoprotein2/high-density-lipoprotein3 cholesterol ratio fell significantly during ursodeoxycholic acid treatment . No significant change occurred in total triglyceride or total phospholipid levels . In the treated group , the proportion of ursodeoxycholic acid  increased ( up to 60 % of total circulating bile acids ) , whereas that of cholic and chenodeoxycholic acids  fell significantly . In conclusion , the cholesterol-lowering effect of ursodeoxycholic acid could be related to an improvement of cholestasis , modifications in cholesterol metabolism or both . Changes in endogenous bile acid composition induced by ursodeoxycholic acid might be the common denominator of these two mechanisms BACKGROUND AND AIMS Despite hypercholesterolemia has been recognized to increase cardiovascular risk in human immunodeficiency virus (HIV)-infected patients , cholesterol-lowering therapy is underused in this population , due to fear of drug-drug interactions with antiretroviral therapy ( ART ) . We investigated the effects of a nutraceutical combination ( NC ) on lipid profile , proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , sub clinical inflammation and arterial stiffness in ART-treated HIV-infected patients . METHODS This was a prospect i ve r and omized open-label trial with a cross-over design including 30 stable HIV-infected patients on ART with low-density lipoprotein cholesterol ( LDL-C ) > 115 mg/dL , not taking lipid-lowering treatment . After a 3-week lipid stabilization period , the effects associated with 3 months of an oral NC containing red yeast rice and berberine vs. no active treatment ( noNC ) were assessed for plasma total cholesterol ( TC ) , LDL-C , high-density lipoprotein cholesterol ( HDL-C ) , triglyceride ( TG ) , lipoprotein(a ) , PCSK9 , high-sensitivity C-reactive protein ( hs-CRP ) levels and aortic pulse wave velocity ( aPWV ) . RESULTS At baseline , significant correlations between PCSK9 levels , age ( rho = -0.51 , p=0.004 ) , waist circumference ( rho = 0.36 , p=0.005 ) and CD4 + cell count ( rho = -0.40 , p=0.027 ) were observed . NC treatment effects corrected for noNC were significant for TC ( -14 % , p<0.001 ) , LDL-C ( -19 % , p<0.001 ) , PCSK9 ( -12 % , p=0.02 ) , hs-CRP ( -14 % , p=0.03 ) and aPWV ( -6 % , p=0.005 ) . No significant effects were observed for HDL-C , TG and lipoprotein(a ) . NC treatment was safe and no significant alterations in muscle , liver and immunovirological parameters were observed . No carry over effect was recorded . CONCLUSIONS The tested NC significantly reduced plasma cholesterol and PCSK9 levels , attenuated sub clinical inflammation and improved arterial stiffness in stable HIV-infected patients on ART
target: In the subgroup of patients with primary biliary cirrhosis  , ursodeoxycholic acid  reduced total cholesterol ( WMD : − 29.86 mg/dL , 95 % CI : -47.39 , − 12.33 , p = 0.001 ) and LDL-C ( WMD : -37.27 mg/dL , 95 % CI : -54.16 , − 20.38 , p < 0.001 ) concentrations without affecting TG and HDL-C. Conclusion This meta- analysis suggests that ursodeoxycholic acid therapy might be associated with significant total cholesterol lowering particularly in patients with primary biliary cirrhosis
background: Objective The aim of this meta- analysis of r and omized placebo-controlled trials was to examine whether ursodeoxycholic acid treatment is an effective lipid-lowering agent .