The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial. Double-blind, controlled trial of propylthiouracil in patients with severe acute alcoholic hepatitis. A randomized placebo controlled trial of vitamin E for alcoholic hepatitis. Insulin and glucagon infusion in acute alcoholic hepatitis: a prospective randomized controlled trial. The prognosis of patients with alcoholic liver disease. An international randomized, placebo-controlled trial on the effect of malotilate on survival. Long-term treatment of alcoholic liver disease with propylthiouracil. Part 2: Influence of drop-out rates and of continued alcohol consumption in a clinical trial. Controlled trial on nutrition supplementation in outpatients with symptomatic alcoholic cirrhosis. Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. [Effect of pentoxifylline on survival, cardiac function and both portal and systemic hemodynamics in advanced alcoholic cirrhosis--a randomized double-blind placebo-controlled trial]. Combination of direct and indirect evidence in mixed treatment comparisons. Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches. Granulocyte Colony-Stimulating Factor in Severe Alcoholic Hepatitis: A Randomized Pilot Study S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: a randomized clinical trial. Steroids or pentoxifylline for alcoholic hepatitis (STOPAH): study protocol for a randomised controlled trial [Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients]. Accelerated improvement of alcoholic liver disease with enteral nutrition. Pentoxifylline versus prednisolone for severe alcoholic hepatitis: a randomized controlled trial. [Treatment of acute alcoholic hepatitis with prednisolone. 45 patients]. S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trial. Failure of colchicine to improve short-term survival in patients with alcoholic hepatitis. Methods for combining randomized clinical trials: strengths and limitations. Pentoxifylline in severe alcoholic hepatitis: a prospective, randomised trial. Nutritional support in hospitalized patients with alcoholic liver disease. Effects of long-term vitamin E supplementation in alcoholic cirrhotics. Randomised controlled double-blind trial of the calcium channel antagonist amlodipine in the treatment of acute alcoholic hepatitis. [Alcohol-induced toxic hepatitis--a "free radical" associated disease. Lowering fatality by adjuvant antioxidant therapy]. Treatment of alcoholic hepatitis with colchicine. Results of a randomized double blind trial. A randomized clinical trial of supplementary parenteral nutrition in jaundiced alcoholic cirrhotic patients. Prednisolone plus S-adenosil-l-methionine in severe alcoholic hepatitis 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. A randomized controlled study of peripheral parenteral nutrition in moderate and severe alcoholic hepatitis. Colchicine treatment of alcoholic cirrhosis: a randomized, placebo-controlled clinical trial of patient survival. A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis. Long-Term Patient Outcome and Quality of Life After Liver Transplantation: Analysis of 20-Year Survivors Pentoxifylline does not decrease short-term mortality but does reduce complications in patients with advanced cirrhosis. Pentoxifylline Plus Prednisolone versus Pentoxifylline Only for Severe Alcoholic Hepatitis: A Randomized Controlled Clinical Trial A randomized, double-blinded, placebo-controlled multicenter trial of etanercept in the treatment of alcoholic hepatitis. Controlled trial of methylprednisolone therapy in severe acute alcoholic hepatitis. Corticosteroid therapy of alcoholic hepatitis: How many studies will it take? Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. Pentoxifylline is ineffective in treating severe alcoholic hepatitis Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone. Controlled trial of nutritional supplementation, with and without branched chain amino acid enrichment, in treatment of acute alcoholic hepatitis. A randomized controlled trial of ursodeoxycholic acid in patients with alcohol‐induced cirrhosis and jaundice A controlled trial of 6-methylprednisolone in acute alcoholic hepatitis. With a note on published results in encephalopathic patients. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. Short- and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: a multicenter randomized trial. Liv.52 in alcoholic liver disease: a prospective, controlled trial. AMINOACID THERAPY OF ALCOHOLIC HEPATITIS Corticosteroid therapy in severe alcoholic hepatitis. A double-blind drug trial. Testosterone treatment of men with alcoholic cirrhosis: a double-blind study. The Copenhagen Study Group for Liver Diseases. Adrenocorticosteroid therapy in alcoholic hepatitis Combination of steroids with infliximab or placebo in severe alcoholic hepatitis: a randomized controlled pilot study. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. Beneficial effects of candesartan, an angiotensin-blocking agent, on compensated alcoholic liver fibrosis - a randomized open-label controlled study. Short-term and long-term survival in patients with alcoholic hepatitis treated with oxandrolone and prednisolone. A randomized trial of antioxidant therapy alone or with corticosteroids in acute alcoholic hepatitis. Effect of parenteral amino acid supplementation on short-term and long-term outcomes in severe alcoholic hepatitis: a randomized controlled trial. Antioxidants versus corticosteroids in the treatment of severe alcoholic hepatitis--a randomised clinical trial. Lack of effect of colchicine in alcoholic cirrhosis: final results of a double blind randomized trial Effect of short-term therapy with propylthiouracil in patients with alcoholic liver disease. Treatment of severe alcoholic hepatitis by infusion of insulin and glucagon: a multicenter sequential trial. Preliminary observations of d-penicillamine therapy in acute alcoholic liver disease. Prednisolone or pentoxifylline for alcoholic hepatitis. Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial. Enteral nutrition with or without N-acetylcysteine in the treatment of severe acute alcoholic hepatitis: a randomized multicenter controlled trial. Pentoxifylline vs. corticosteroid to treat severe alcoholic hepatitis: a randomised, non-inferiority, open trial. Influence of Reported Study Design Characteristics on Intervention Effect Estimates From Randomized, Controlled Trials
BACKGROUND Alcoholic hepatitis ( AH ) is a distinct presentation of alcoholic liver disease arising in patients who have been drinking to excess for prolonged periods , which is characterised by jaundice and liver failure . Severe disease is associated with high short-term mortality . Prednisolone and pentoxifylline ( PTX ) are recommended in guidelines for treatment of severe AH , but trials supporting their use have given heterogeneous results and controversy persists about their benefit . OBJECTIVES The aim of the clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis trial was to resolve the clinical dilemma on the use of prednisolone or PTX . DESIGN The trial was a r and omised , double-blind , 2 × 2 factorial , multicentre design . SETTING Sixty-five gastroenterology and hepatology inpatient units across the UK . PARTICIPANTS Patients with a clinical diagnosis of AH who had a Maddrey 's discriminant function value of ≥ 32 were r and omised into four arms : A , placebo/placebo ; B , placebo/prednisolone ; C , PTX/placebo ; and D , PTX/prednisolone . Of the 5234 patients screened for the trial , 1103 were r and omised and after withdrawals , 1053 were available for primary end-point analysis . INTERVENTIONS Those allocated to prednisolone were given 40 mg daily for 28 days and those allocated to PTX were given 400 mg three times per day for 28 days . OUTCOMES The primary outcome measure was mortality at 28 days . Secondary outcome measures included mortality or liver transplant at 90 days and at 1 year . Rates of recidivism among survivors and the impact of recidivism on mortality were assessed . RESULTS At 28 days , in arm A , 45 of 269 ( 16.7 % ) patients died ; in arm B , 38 of 266 ( 14.3 % ) died ; in arm C , 50 of 258 ( 19.4 % ) died ; and in arm D , 35 of 260 ( 13.5 % ) died . For PTX , the odds ratio for 28-day mortality was 1.07 [ 95 % confidence interval ( CI ) 0.77 to 1.40 ; p = 0.686 ) ] and for prednisolone the odds ratio was 0.72 ( 95 % CI 0.52 to 1.01 ; p = 0.056 ) . In the logistic regression analysis , accounting for indices of disease severity and prognosis , the odds ratio for 28-day mortality in the prednisolone-treated group was 0.61 ( 95 % CI 0.41 to 0.91 ; p = 0.015 ) . At 90 days and 1 year there were no significant differences in mortality rates between the treatment groups . Serious infections occurred in 13 % of patients treated with prednisolone compared with 7 % of controls ( p = 0.002 ) . At the 90-day follow-up , 45 % of patients reported being completely abstinent , 9 % reported drinking within safety limits and 33 % had an unknown level of alcohol consumption . At 1 year , 37 % of patients reported being completely abstinent , 10 % reported drinking within safety limits and 39 % had an unknown level of alcohol consumption . Only 22 % of patients had attended alcohol rehabilitation treatment at 90 days and 1 year . CONCLUSIONS We conclude that prednisolone reduces the risk of mortality at 28 days , but this benefit is not sustained beyond 28 days . PTX had no impact on survival . Future research should focus on interventions to promote abstinence and on treatments that suppress the hepatic inflammation without increasing susceptibility to infection . TRIAL REGISTRATION This trial is registered as EudraCT 2009 - 013897 - 42 and Current Controlled Trials IS RCT N88782125 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 19 , No. 102 . See the NIHR Journals Library website for further project information . The NIHR Clinical Research Network provided research nurse support and the Imperial College Biomedical Research Centre also provided funding Sixty-seven patients entered a double-blind , controlled trial to evaluate the efficacy of propylthiouracil treatment in severe alcoholic hepatitis . Twenty-three percent ( 7 of 31 ) given propylthiouracil and 19 % ( 7 of 36 ) given placebo  died during the 6-wk study . Propylthiouracil treatment did not reduce the frequency and incidence of complications in alcoholic hepatitis , but induced hypothyroidism in 4 patients . Treatment produced no beneficial effect on any of the hepatic biochemical tests . We were unable to show any beneficial effect of propylthiouracil treatment on morbidity and mortality in patients with severe acute alcoholic hepatitis BACKGROUND / AIMS The effect of vitamin E administration on clinical and laboratory parameters of liver function and on markers of fibrogenesis was assessed in patients with mild to moderate alcoholic hepatitis in a double blind placebo controlled r and omized trial . METHODS Twenty-five patients received 1000  I.U.  of vitamin E per day , while 26 patients received placebo for 3 months . The patients were followed for 1 year after entry into the trial . RESULTS Vitamin E did not result in significant greater decreases in serum aminotransferases and serum bilirubin or in greater increases in serum albumin as compared with placebo .  Prothrombin time did not change , while serum creatinine remained in the normal range . Monocyte nuclear nuclear factor-kappa B binding activity decreased in patients who remained abstinent , regardless of whether they received vitamin E. As regards markers of hepatic fibrogenesis , vitamin E treatment decreased serum hyaluronic acid ( P<0.05 ) while serum aminoterminal peptide of type III procollagen did not change in either group . Four patients in the treatment group and five in the placebo group died during the 1-year study . CONCLUSIONS Vitamin E treatment improves serum hyaluronic acid but has no beneficial effects on tests of liver function in patients with mild to moderate alcoholic hepatitis In a r and omized , controlled trial to investigate the possible benefit of insulin and glucagon therapy in severe acute alcoholic hepatitis , 86 patients were r and omized to receive 30 U insulin and 3 mg glucagon in 250 ml 5 % dextrose over 12 hr each day for 3 wk or a similar regime of identical placebo . No significant differences were seen in patients ' clinical characteristics and disease severity in the treated and placebo groups . Of the 43 patients receiving insulin and glucagon , 15 ( 35 % ) died within 4 wk of r and omization , compared with 14 deaths ( 33 % ) in the control patients ( p = not significant ) . When the patients surviving the first 4 wk were examined there were five more deaths in the treatment group , compared with one death in the control group at 6-mo follow-up ( p = not significant ) . No significant differences in the frequency of short-term or long-term complications of alcoholic liver disease or relapse to alcohol were seen when the two groups were compared , although hypoglycemia was seen in six patients during infusion of insulin and glucagon . Similarly , no significant differences were seen in the improvement in clinical or biochemical features at 4 wk and at 6 mo in survivors when the insulin and glucagon-treated patients were compared with patients in the placebo group . This study does not confirm previous reports that insulin and glucagon infusion improves the outcome of severe acute alcoholic hepatitis The aim of this study was to examine the effect of malotilate on survival in patients with alcoholic liver disease and to determine prognostic variables for survival .  Four hundred and seven patients with alcoholic liver diseases , from seven European liver units , entered a r and omized placebo-controlled , double-blind trial : 140 patients received malotilate 1500 mg/day , 133 patients received 750 mg/day , and 134 patients received placebo . The patients were included in the study over a period of 3 1/2 years , and the study was closed 1 year after the entry of the last patient . Eighty-four patients died ( 35 , 19 , 30 patients in groups 1500 mg/day , 750 mg/day , and placebo , respectively ) . Survival was slightly better in the 750 mg/day group than in the two other treatment groups , when tested by conventional log-rank tests ( p = 0.06 ) . However , a treatment effect was supported by a highly significant ( p = 0.006 ) non-proportionality of the death intensity in patients receiving 750 mg/day against those receiving either 1500 mg/day or placebo . Prognostic variables for survival were evaluated using the multiple Cox regression analysis of clinical and laboratory variables and with or without liver histology variables , as determined at entry into the study . The analysis was stratified for the three treatment regimens . In the analysis including liver histology variables , independent significant prognostic variables were : years of high alcohol intake , prothrombin index , alkaline phosphatases , creatinine , immunoglobulin M , white blood cell count , and liver cell steatosis . In the analysis without liver histology variables , prognostic variables were : years of high alcohol intake , prothrombin index , alkaline phosphatases , creatinine , and immunoglobulin Although propylthiouracil has previously been shown to reduce the risk of mortality in alcoholic liver disease by 60 % , generalized use of propylthiouracil for this condition has not occurred . Additional data are therefore presented on four aspects to provide a better assessment of its therapeutic effectiveness . First , the characteristics and the prognosis of dropouts were virtually identical in both the drug and placebo groups . Also the methodology and analysis employed , were design ed to control for dropouts , thus providing an accurate interpretation of the outcome . Secondly , since 97 % of the patients continued to drink , abstinence was not a precondition for the beneficial effect of propylthiouracil . However , the beneficial effect was observed most clearly in those patients who continued to drink at lower levels , whereas lower level drinking per se did not afford protection in placebo patients . Thirdly , serious side effects or clinical hypothyroidism occurred extremely rarely in these patients , many of whom have now received propylthiouracil for over 4 years . Fourthly , we discuss why the outcome in long-term clinical trials in alcoholic liver disease can not be compared with effects observed in clinical trials lasting only a few weeks . Journal of Hepatology A controlled trial on nutrition supplementation in ambulatory patients with decompensated alcoholic liver disease was carried out during 1 year . Fifty-one patients were studied ; 26 were assigned to an experimental group receiving a daily supplement of 1000 kcal and 34 g of proteins given as a casein-based enteral nutrition product and 25 to a control group receiving one placebo capsule .  Patients were examined in a special clinic once a month or more if required . Sixty-eight percent of patients admitted to alcohol ingestion or had alcohol in urine sample s on at least one occasion . Dietary recalls showed a significantly higher protein and caloric intake in case patients subjects ( p < .0001 ) . Nine patients  died during the study , three case patients and six control patients ( p = NS ) . The frequency of hospitalizations was significantly less in the experimental group . This difference was attributed to a reduction in severe infections . Mid-arm circumference , serum albumin concentration , and h and grip strength improved earlier in case patients , although both groups had a significant improvement in these parameters . Bilirubin and aspartate aminotransferase decreased and prothrombin time increased significantly in both groups during the study period , without differences between groups . It is concluded that nutrition support decreases nutrition-associated complications in patients with alcoholic liver disease 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 > or = 32 ) entered a 4-week double-blind r and omized trial of PTX ( 400 mg orally 3 times daily ) vs. placebo . Primary endpoints of the study were the effect of PTX on ( 1 ) short-term survival and ( 2 ) progression to hepatorenal syndrome . On r and omization , there were no differences in demographic and clinical characteristics or laboratory values ( including TNF ) between the 2 groups . RESULTS Twelve ( 24.5 % ) of the 49 patients who received PTX and 24 ( 46.1 % ) of the 52 patients who received placebo  died during the index hospitalization ( P = 0.037 ; relative risk , 0.59 ; 95 % confidence interval , 0.35 - 0.97 ) . Hepatorenal syndrome was the cause of death in 6 ( 50 % ) and 22 ( 91.7 % ) patients ( P = 0.009 ; relative risk , 0.29 ; 95 % confidence interval , 0.13 - 0.65 ) . Three variables ( age , creatinine level on r and omization , and treatment with PTX ) were independently associated with survival . TNF values on r and omization were not predictive of survival ; however , during the study period they increased markedly in nonsurvivors compared with survivors in both groups . CONCLUSIONS Treatment with PTX improves short-term survival in patients with severe alcoholic hepatitis . The benefit appears to be related to a significant decrease in the risk of developing hepatorenal syndrome . Increasing TNF levels during the hospital course are associated with an increase in mortality rate OBJECTIVE To assess the effect of pentoxiphylline ( a potent inhibitor of tumor necrosis factor alpha ) on survival , on systemic and portal hemodynamics , and on cardiac function in patients with alcoholic cirrhosis . DESIGN A r and omized double-blind placebo-controlled trial . SETTING A single center using parallel groups of patients to compare pentoxiphylline with placebo . PATIENTS We recruited 24 patients with alcoholic cirrhosis ( 8 Child-Pugh B and 16 Child-Pugh C ) . INTERVENTIONS Patients were r and omly assigned to receive pentoxiphylline ( 400 mg tid ; n = 12 ) or placebo ( n = 12 ) over a 4-week period . OUTCOME MEASURES The primary outcome was to extend short-term and long-term survival . Secondary outcomes included hemodynamic benefits ( improvement in cardiac function and /or systemic vascular resistance index , or decrease in portal pressure ) . RESULTS Portal pressure and cardiac function remained unchanged and there were no significant differences in short-term or long-term survival between treatment and placebo groups . The group on pentoxiphylline increased systemic vascular resistance and decreased cardiac indices ( from 1,721 + /- 567 to 2,082 + /- 622 dyn.sec(-1 ) cm(-5 ) m(-2 ) and from 4.17 + /- 1.4 to 3.4 + /- 0.9 l.m(-2 ) , p = 0.05 ) . CONCLUSIONS Although pentoxiphylline seems to provide some short-term hemodynamic benefits in patients with advanced alcoholic cirrhosis , this drug has no effect on survival or portal pressure in these patients Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials OBJECTIVES : Severe alcoholic hepatitis has high short-term mortality . The aim of this study was to test the hypothesis that treatment of patients with alcoholic hepatitis with granulocyte colony-stimulating factor ( G-CSF ) might mobilize bone marrow – derived stem cells and promote hepatic regeneration and thus improve survival . METHODS : Forty-six patients with severe alcoholic hepatitis were prospect ively r and omized in an open study to st and ard medical therapy ( SMT ) plus G-CSF ( group A ; n=23 ) at a dose of 5 μg/kg subcutaneously every 12 h for 5 consecutive days or to SMT alone ( group B ; n=23 ) at a tertiary care center . We assessed the mobilization of CD34 + cells on day 6 , Child-Turcotte-Pugh ( CTP ) , model for end-stage liver disease ( MELD ) , and modified Maddrey ’s discriminant function ( mDF ) scores , and survival until day 90 . RESULTS : There was a statistically significant increase in the number of CD34 + cells in peripheral blood in group A as compared with group B ( P=0.019 ) after 5 days of G-GSF therapy . There was a significant reduction in median Δ change% in CTP , MELD , and mDF at 1 , 2 , and 3 months in group A as compared with group B ( P<0.05 ) . There was marked improvement in survival in group A as compared with group B ( 78.3 % vs. 30.4 % ; P=0.001 ) at 90 days . CONCLUSIONS : G-CSF is safe and effective in the mobilization of hematopoietic stem cells and improves liver function as well as survival in patients with severe alcoholic hepatitis BACKGROUND / AIM The efficacy of S-adenosylmethionine ( AdoMet ) in the treatment of liver cell injury has been demonstrated in several experimental models . The aim of this study was to investigate the effects of AdoMet treatment in human alcoholic liver cirrhosis . METHODS A r and omized , double-blind trial was performed in 123 patients treated with AdoMet ( 1200 mg/day , orally ) or placebo for 2 years . All patients had alcoholic cirrhosis , and histologic confirmation of the diagnosis was available in 84 % of the cases . Seventy-five patients were in Child class A , 40 in class B , and 8 in class C. Sixty-two patients received  AdoMet and 61 received placebo . RESULTS At inclusion into the trial no significant differences were observed between the two groups with respect to sex , age , previous episodes of major complications of cirrhosis , Child classification and liver function tests . The overall mortality/liver transplantation at the end of the trial decreased from 30 % in the placebo group to 16 % in the AdoMet group , although the difference was not statistically significant ( p = 0.077 ) . When patients in Child C class were excluded from the analysis , the overall mortality/liver transplantation was significantly greater in the placebo group than in the AdoMet group ( 29 % vs. 12 % , p = 0.025 ) , and differences between the two groups in the 2-year survival curves ( defined as the time to death or liver transplantation ) were also statistically significant ( p = 0.046 ) . CONCLUSIONS The present results indicate that long-term treatment with AdoMet may improve survival or delay liver transplantation in patients with alcoholic liver cirrhosis , especially in those with less advanced liver disease IMPORTANCE Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis , a life-threatening disease . The benefit of their combination is unknown . OBJECTIVE To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone . DESIGN , SETTING , AND PARTICIPANTS Multicenter , r and omized , double-blind clinical trial conducted between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven alcoholic hepatitis , as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32 . Duration of follow-up was 6 months . The last included patient completed the study in October 2010 . None of the patients were lost to follow-up for the main outcome . INTERVENTION Patients were r and omly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day ( n=133 ) for 28 days , or 40 mg of prednisolone and matching placebo ( n=137 ) for 28 days . MAIN OUTCOMES AND MEASURES Six-month survival , with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model , which defines treatment nonresponders after 7 days of initiation of treatment . RESULTS In intention-to-treat analysis , 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups ( 69.9 % [ 95 % CI , 62.1%-77.7 % ] vs 69.2 % [ 95 % CI ; 61.4%-76.9 % ] , P = .91 ) , corresponding to 40 vs 42 deaths , respectively . In multivariable analysis , only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival . At 7 days , response to therapy assessed by the Lille model was not significantly different between the 2 groups ( Lille model score , 0.41 [ 95 % CI , 0.36 - 0.46 ] vs 0.40 [ 95 % CI , 0.35 - 0.45 ] , P = .80 ) . The probability of being a responder was not different in both groups ( 62.6 % [ 95 % CI , 53.9%-71.3 % ] vs 61.9 % [ 95 % CI , 53.7%-70.3 % ] , P = .91 ) . The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone and the placebo-prednisolone groups ( 8.4 % [ 95 % CI , 4.8%-14.8 % ] vs 15.3 % [ 95 % CI , 10.3%-22.7 % ] , P = .07 ) . CONCLUSION AND RELEVANCE In patients with alcoholic hepatitis , 4-week treatment with pentoxifylline and prednisolone , compared with prednisolone alone , did not result in improved 6-month survival . The study may have been underpowered to detect a significant difference in incidence of hepatorenal syndrome , which was less frequent in the group receiving pentoxifylline . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01214226 Abstract Background Alcoholic hepatitis is the most florid presentation of alcohol-related liver disease . In its severe form , defined by a Maddrey ’s discriminant function ( DF ) ≥32 , the 28-day mortality rate is approximately 35 % . A number of potential treatments have been subjected to clinical trials , of which two , corticosteroids and pentoxifylline , may have therapeutic benefit . The role of corticosteroids is controversial as trial results have been inconsistent , whereas the role of pentoxifylline requires confirmation as only one previous placebo-controlled trial has been published . Methods / design STOPAH is a multicentre , double-blind , factorial ( 2 × 2 ) trial in which patients are r and omised to one of four groups : 1.Group A :  placebo / placebo2.Group B :  placebo / prednisolone3.Group C  : pentoxifylline / placebo4.Group D : pentoxifylline / prednisolone The trial aims to r and omise 1,200 patients with severe alcoholic hepatitis , in order to provide sufficient power to determine whether either of the two interventions is effective . The primary endpoint of the study is mortality at 28 days , with secondary endpoints being mortality at 90 days and 1 year . Discussion STOPAH aims to be a definitive study to resolve controversy around the existing treatments for alcoholic hepatitis . Eligibility criteria are based on clinical parameters rather than liver biopsy , which are aligned with st and ard clinical practice in most hospitals . The use of a factorial design will allow two treatments to be evaluated in parallel , with efficient use of patient numbers to achieve high statistical power . Trial registration EudraCT reference number : 2009 - 013897 - 42IS RCT N reference number : IS RCT A r and omized double-blind trial of silymarin versus placebo was carried out in 116 patients with histologically proven alcoholic hepatitis , 58 of them with cirrhosis . Patients were not included in case of hepatic encephalopathy , contraindication to percutaneous liver biopsy , hepatocellular carcinoma , evident lack of discipline or refusal to enter the trial . Fifty-seven patients received silymarin orally 420 mg/day and 59 received placebo during 3 months . Biologic parameters were assessed in the serum , and a percutaneous liver biopsy was obtained at the start of the trial and 3 months later . Histologic scores of alcoholic hepatitis and fibrosis were established on each biopsy specimen by two independent pathologists . The 2 groups were comparable at inclusion ; 26 p. 100 of patients were lost to follow-up at 3 months , abstinence was obtained in 46 p. 100 of patients at the end of the trial . These percentages were similar in the two groups . Four patients died of hepatic failure during the trial , 3 in the placebo group . Significant improvement in the score of alcoholic hepatitis and serum amino transferase activity , was noted in both groups during the trial , irrespective of treatment with silymarin or placebo . No side-effects were noted . Our results suggest that silymarin 420 mg/d is not clinical ly relevant in the treatment of moderate alcoholic hepatitis This prospect i ve study compared the effects of tube-fed nutrition with those of a regular diet in alcoholic liver disease . The high prevalence of malnutrition in patients with alcoholic liver disease requires clarification of the benefits of aggressive nutritional support . Patients were r and omly assigned a regular diet without or with tube-fed supplementation , delivering 1.5 g/kg protein and 167 kJ/kg daily . Comparisons of encephalopathy , antipyrine clearance , metabolic rate , and biochemical parameters were performed weekly for 4 weeks . Sixteen patients receiving enteral supplementation had antipyrine half-life ( 50 % vs. 3 % reduction ) , serum bilirubin ( 25 % vs. 0 % reduction ) , and median encephalopathy scores that improved more rapidly than those of controls . Initially , 15 controls did not consume adequate calories to meet measured resting energy expenditure . Aggressive nutritional intervention accelerated improvement in alcoholic liver disease . Adverse effects did not offset the demonstrated benefits of a 2-cal/mL , casein-based tube-fed supplement . These findings support the use of st and ard , casein-based solutions in the treatment of alcoholic liver disease and as the control condition for future studies AIM To compare the efficacy of pentoxifylline and prednisolone in the treatment of severe alcoholic hepatitis , and to evaluate the role of different liver function scores in predicting prognosis . METHODS Sixty-eight patients with severe alcoholic hepatitis ( Maddrey score > or = 32 ) received pentoxifylline ( n = 34 , group I ) or prednisolone ( n = 34 , group II ) for 28 d in a r and omized double-blind controlled study , and subsequently in an open study ( with a tapering dose of prednisolone ) for a total of 3 mo , and were followed up over a period of 12 mo . RESULTS Twelve patients in group II died at the end of 3 mo in contrast to five patients in group I. The probability of dying at the end of 3 mo was higher in group II as compared to group I ( 35.29 % vs 14.71 % , P = 0.04 ; log rank test ) . Six patients in group II developed hepatorenal syndrome as compared to none in group I. Pentoxifylline was associated with a significantly lower model for end-stage liver disease ( MELD ) score at the end of 28 d of therapy ( 15.53 + /- 3.63 vs 17.78 + /- 4.56 , P = 0.04 ) . Higher baseline Maddrey score was associated with increased mortality . CONCLUSION Reduced mortality , improved risk-benefit profile and renoprotective effects of pentoxifylline compared with prednisolone suggest that pentoxifylline is superior to prednisolone for treatment of severe alcoholic hepatitis Whether or not prednisolone ( or prednisone ) should be used to treat alcoholic hepatitis remains controversial . This new controlled study performed on 45 patients with steatosis , fibrosis or cirrhosis of the liver suggests that prednisolone is not effective : after a 3-month follow-up clinical course , biochemical alterations , anatomical lesions and portal hypertension were the same in patients treated with prednisolone and in those who did not receive that drug BACKGROUND S-adenosyl-L-methionine ( SAM ) is the methyl donor for all methylation reactions and regulates the synthesis of glutathione , the main cellular antioxidant . Previous experimental studies suggested that SAM may benefit patients with established alcoholic liver diseases ( ALDs ) . The aim of this study was to determine the efficacy of SAM in treatment for ALD in a 24-week trial . The primary endpoints were changes in serum aminotransferase levels and liver histopathology scores , and the secondary endpoints were changes in serum levels of methionine metabolites . METHODS We r and omized 37 patients with ALD to receive 1.2 g of SAM by mouth or placebo daily . Subjects were required to remain abstinent from alcohol drinking . A baseline liver biopsy was performed in 24 subjects , and a posttreatment liver biopsy was performed in 14 subjects . RESULTS Fasting serum SAM levels were increased over timed intervals in the SAM treatment group . The entire cohort showed an overall improvement of AST , ALT , and bilirubin levels after 24 weeks of treatment , but there were no differences between the treatment groups in any clinical or biochemical parameters nor any intra- or intergroup differences or changes in liver histopathology scores for steatosis , inflammation , fibrosis , and Mallory-Denk hyaline bodies . CONCLUSIONS Whereas abstinence improved liver function , 24 weeks of therapy with SAM was no more effective than placebo in the treatment for ALD Colchicine treatment was used in this r and omized placebo-controlled trial in patients with severe acute alcoholic hepatitis [ serum bilirubin greater than or equal to 5 mg/dL ( 85.5 mumol/L ) mean , 17.5 + /- 7.5 mg/dL ( 299.25 + /- 128.25 mumol/L ) ] . Hospitalization mortality and morbidity and the effect on biochemical test results were the end points of the treatment . Patients in the two groups were evenly matched by demographics and laboratory test results . Mean time to study entry was less than 7 days from admission . The duration of the trial was 30 days . Thirty-six patients ( 24 men , 12 women ) received colchicine ( 1 mg orally every morning ) and 36 ( 25 men , 11 women ) received an identical placebo . Seven ( 19 % ) colchicine-treated and six ( 17 % ) control patients died during the index hospitalization after a mean of 17.4 + /- 10.8 and 17.8 + /- 5.3 days , respectively ( NS ) . During a 4-month follow-up period from entry into the trial , there were two additional deaths in each group . No differences between placebo- and colchicine-treated patients were observed in any of the laboratory parameters ( serum bilirubin , aspartate transaminase , alanine transaminase , prothrombin activity , albumin , white blood cell count , hemoglobin , and creatinine ) that were followed up over the 30-day treatment period . The frequency of complications did not differ statistically between the two groups . This study showed no effect of colchicine treatment on mortality and morbidity of severe alcoholic hepatitis . Colchicine can not be recommended for the treatment of patients with alcoholic hepatitis Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . BACKGROUND Role of corticosteroids in treatment of  severe alcoholic hepatitis ( SAH ) is controversial . Pentoxifylline ( PTX ) , an inhibitor of TNF , has also been shown to decrease short term mortality in SAH . Aim of this study was to evaluate the effect of PTX on short term mortality , renal and hepatic functions in patients with SAH . METHODS Fifty patients with SAH { Maddrey 's Discriminant Function ( DF ) > or = 32 } were prospect ively enrolled . Twenty five patients received  PTX  ( 400 mg orally , three times a day ) , and 25 received placebo for 4 weeks . Serum tumor necrosis factor ( TNF ) was measured in both groups . RESULTS Baseline characteristics of the two groups were similar . At 4 weeks , mortality in PTX group was lower than that in controls { 20 % ( 5/25 ) versus 40 % ( 10/25 ) respectively ; p = 0.216 ; RR 0.5 ; 95 % CI 0.19 - 1.25}. Renal failure was the cause of mortality in 20 % ( 1/5 ) patients in PTX group , and 70 % ( 7/10 ) in controls ( p = 0.11 ) . Significant reduction in urea , creatinine , DF and TNF was noted in PTX group . Reduction in TNF did not correlate with reduction in creatinine or DF . CONCLUSIONS In patients with SAH , PTX leads to a significant improvement in renal and hepatic functions , and a trend towards decreased short term mortality The effects of a nutritional support in hospitalized patients with alcoholic cirrhosis and liver failure were studied in a controlled protocol . Thirty-six patients were included , 17 were r and omly assigned to an experimental group and the rest to a control group . Experimentals received a diet aim ing at 50 kcal ( 209 kJ)/kg bodyweight/d and 1.5 g protein/kg bodyweight/d ( as proteins of high biological value ) . Controls received the st and ard diet prescribed by the attending physician . The severity of liver failure and the nutritional status on admission were similar in both groups . The measured energy intake in controls was 1813 + /- 121 kcal/d ( 7589 + /- 506 kJ/d ) and 2707 + /- 71 kcal/d ( 1131 + /- 297 kJ/d ) in experimentals ( P less than 0.001 ) . The protein intake in controls was 47 + /- 3.8 g/d and in experimentals 80 + /- 3 g/d ( P less than 0.001 ) . There were seven deaths during the study period ( two experimentals and five controls ) . No differences were observed in the evolution of liver failure , hepatic encephalopathy or nutritional status between both study groups . It is concluded that a higher energy and protein intake in these patients does not have adverse effects and is associated with a non-significant reduction in mortality OBJECTIVE Alcohol ingestion promotes lipoperoxidation and alters cellular antioxidant mechanisms . Alpha-tocopherol levels decrease in alcoholics as severity of liver damage increases . The aim of this protocol was to study the effects of a long-term oral 500 mg vitamin E daily supplementation in decompensated ambulatory alcoholic cirrhotics . PATIENTS AND METHODS 67 subjects were included in this double blind trial ; 33 patients received vitamin E and 34 patients received placebo tablets of identical appearance during 1 year . Each month , the patients were seen by a nurse practitioner who was in charge of detecting alcohol ingestion and checking adherence to treatment . Every 3 months , the patients underwent a medical examination , and blood sample s were taken for clinical laboratory analysis and serum vitamin E measurement . RESULTS Alpha-tocopherol levels were significantly lower in patients with more severe liver disease . This difference was not significant when vitamin E levels were corrected by cholesterol . Oral supplementation significantly increased serum vitamin E levels in the experimental group . Alcohol ingestion and hospitalization rates were similar in both groups . Life table analysis did not show significant differences in mortality between the two groups . DISCUSSION Vitamin E supplementation with adequate doses of an alpha-tocopheryl acetate formulation during 1 year did not influence hepatic laboratory parameters , mortality or hospitalization rates of decompensated alcoholic cirrhotics , although serum levels of the vitamin significantly increased BACKGROUND / AIMS Calcium channel blockers have a hepatoprotective action in animal models of alcohol-induced liver injury but their effect in alcoholic liver disease in humans has not been previously investigated . We have conducted a r and omised , placebo-controlled trial to investigate the possible benefit of the calcium channel blocker amlodipine in terms of 4-week survival in hospitalised patients with severe acute alcoholic hepatitis . METHODS Sixty-two patients with acute alcoholic hepatitis were r and omised to receive 5 - 10 mg amlodipine each day for 1 year or an identical capsule containing placebo . In 36 ( 58 % ) , acute alcoholic hepatitis was confirmed on biopsy and in the remainder on clinical and laboratory criteria . There were no statistically significant differences in clinical characteristics and disease severity in the treated and placebo groups . RESULTS Of the 32 patients receiving amlodipine , there were six deaths ( 19 % ) in the first 4 weeks compared with seven ( 23 % ) of the placebo patients ( p=0.329 ) . Causes of death were similar in the amlodipine and control groups , with liver failure predominant . Analysis by the Cox proportional hazards model after adjustment for other prognostic factors showed survival was not significantly influenced by active treatment ( p=0.07 ) . One patient in each group was withdrawn because of the development of hypotension , but this did not recur on re introduction of the capsules . CONCLUSIONS This study shows that calcium channel blockers are well tolerated with few side effects in advanced alcoholic liver disease , but there is no conclusive evidence from this study that calcium channel blockers are helpful in the treatment of alcoholic hepatitis Toxic liver diseases coincide with oxidative stress correlating positively with the seriousness of the course of disease . For the purpose of elucidating the pathogenic significance of an increased radical generation . 56 patients suffering from acute alcohol-toxic hepatitis of the clinical grade of seriousness B and C according to Child/Pugh were classified r and omly into antioxidant subgroups ( n = 31 ) and control groups (= 25 ) . The basis therapy being identical , the patients of the antioxidant group received additionally 600 mg of D-alpha tocopherol per day , 200 micrograms of selenium and 12 mg of zinc . Due to the supplementation of antioxidants there were quicker significant changes in the concentration of bilirubin , malondialdehyde and of ammonia in the serum . In comparison with the control group the length of stay in hospital could be reduced by 6 days . In the control group the mortality rates amounted to 40 % ( 10 of 25 ) , in the antioxidant group to 6.5 % ( 2 of 31 ) . The results confirm the pathogenic significance of oxidative stress in alcohol-toxic liver disease because a distinct improvement of prognosis could be achieved by using a low-cost adjuvant antioxidant supplementation A r and omized double-blind trial of colchicine vs placebo was conducted in 67 patients with histologically proven alcoholic hepatitis , 33 of whom had cirrhosis . Patients with hepatic encephalopathy , ascites , protracted prothrombin time , severe thrombocytopenia , hepatocellular carcinoma , evident lack of discipline or refusal to participate in the trial were not included . Thirty-three patients received colchicine ( 1 mg/day ) and 34 received placebo for 6 months . Blood parameters including N-terminal peptide of type III procollagen were assessed in the serum , and a percutaneous liver biopsy was performed at the start of the trial and after 3 and 6 months . Alcoholic hepatitis and fibrosis scores were established for each biopsy specimen . Twenty-eight percent of patients were lost to follow-up at 3 months , and fifty-two percent at 6 months . One patient died of liver failure . Fifty-eight percent of patients were abstaining from alcohol at 3 months and fifty percent at 6 months . No significant effect of treatment was noted . Nevertheless , improvement in alcoholic hepatitis core at 3 months was more important in the colchicine group than in the placebo group . No side-effects were noted except transient diarrhea . Our results suggest that colchicine has no important effect on the course of alcoholic hepatitis . A trial including of at least 260 patients might be necessary for the observed alcoholic hepatitis score difference at 3 months , favoring colchicine , to be statistically significant Between March 1982 and September 1983 , 40 in patients ( 25 men and 15 women , mean age 53 years ) with alcoholic cirrhosis and total serum bilirubin greater than or equal to 5 mg per dl were studied . Those with hepatocellular carcinoma , renal failure , hyponatremia , septicemia , spontaneous bacterial peritonitis , gastrointestinal bleeding , and hepatic coma were excluded . Patients were studied for 28 days . The two groups were offered an oral diet containing 40 kcal per kg per day . Patients in the supplementary parenteral nutrition group received 40 kcal per kg per day and 200 mg nitrogen per kg per day using a central catheter . The major endpoint was total serum bilirubin on Day 28 . On admission , serum bilirubin was not significantly different in the two groups : oral group , 12.5 + /- 6.6 mg per dl ; supplementary parenteral nutrition group , 12.3 + /- 8.5 mg per dl . On Day 28 , serum bilirubin was lower in the supplementary parenteral nutrition group ( 2.5 + /- 1.4 mg per dl ) than in the oral group ( 4.1 + /- 2.2 mg per dl ) ( p less than 0.02 ) . Serum bilirubin was also lower in the supplementary parenteral nutrition group than in the oral group on Days 7 , 14 and 21 ( p less than 0.05 ) . Analysis of covariance , considering serum bilirubin on admission and at r and omization and time between admission and r and omization , confirmed these results . On Day 28 , anthropometric parameters , serum transferrin , prealbumin and retinol-binding protein were higher in the supplementary parenteral nutrition group , but the differences were not significant . Serum albumin was significantly lower in the supplementary parenteral nutrition group . The incidence of encephalopathy and sepsis was not significantly different between the two groups Purpose / background Severe alcoholic hepatitis ( AH ) is a life-threatening liver disease with a potential of 30–40 % mortality at 1 month . While steroids remain to be a first line therapy , they provide only about 50 % survival benefit . The aim of the study was to evaluate the efficacy of glucocorticoids plus S-adenosylmethionine ( SAMe ) , as compared to glucocorticoids alone , in patients with severe alcoholic hepatitis . Methods Forty patients with severe AH were r and omized in two groups and enrolled in the prospect i ve trial . Group 1 ( n = 20 ) patients received prednisolone 40 mg/daily per os , and group 2 ( n = 20 ) patients were managed with prednisolone 40 mg/daily per os plus SAMe 800 mg i.v . treatment . Duration was 28 days . Results The response rate assessed by Lille model was significantly higher in the prednisolone plus SAMe group ( 19 of 20 ; 95 % ) than in the prednisolone group ( 13 of 20 ; 65 % ) , p = 0.044 . Two ( 10 % ) patients died , both from the prednisolone group . There were no lethal outcomes in the prednisolone plus SAMe group . The Kaplan – Meier method showed no significant differences between the two groups ( p = 0.151 , log-rank ) . Hepatorenal syndrome ( HRS ) occurred in 20 % in the prednisolone group ( 4 of 20 patients ) while no HRS cases were registered in the prednisolone plus SAMe group ( p = 0.035 ) . Conclusions Management of severe alcoholic hepatitis with prednisolone plus SAMe was associated with better therapy response ( p = 0.044 ) and less frequent HRS occurrence ( p = 0.035 ) . Mortality was not significantly lower in the prednisolone – SAMe group than in the prednisolone-only group at 28 days ( 10 vs. 0 % , p = 0.151 ) 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 We performed a controlled trial of peripheral hyperalimentation in moderate and severe alcoholic hepatitis to determine whether improvement in survival and liver function could be obtained . Twelve patients with moderate and 22 with severe alcoholic hepatitis were r and omized to 28 days of peripheral parenteral nutrition ( PPN ) or st and ard therapy ( ST ) . In the moderate group , six were treated with each therapy . In the severe group , 10 were treated with PPN and 12 with ST .  Routine liver tests , hepatocyte function ( galactose elimination capacity ) , estimated hepatic blood flow ( galactose clearance ) and assessment of ascites and encephalopathy were performed at r and omization and at 28 days . Groups were equally matched at r and omization . In the moderate group PPN produced no improvement in morbidity ( liver tests ) and mortality ( no deaths ) . In the severe group there were seven deaths ( 4 PPN , 3 ST ) . PPN produced greater improvement than ST in serum bilirubin and transferrin concentrations and a trend toward greater improvement in prothrombin time , serum albumin and galactose elimination capacity .  PPN had no deleterious effect on encephalopathy or ascites as only ST patients developed ascites or encephalopathy after r and omization . We conclude that PPN compared to ST ( 1 ) provides no benefit in moderate alcoholic hepatitis , but ( 2 ) did more rapidly improve morbidity ( liver tests ) and probably liver function in severe alcoholic hepatitis ; ( 3 ) PPN did not improve early mortality , and ( 4 ) it had no deleterious effect on encephalopathy or ascites BACKGROUND & AIMS Colchicine improved survival and reversed cirrhosis in several small clinical trials . We compared the efficacy and safety of long-term colchicine , as compared with placebo , in patients with advanced alcoholic cirrhosis . METHODS Five hundred forty-nine patients with advanced ( Pugh B or C ) alcoholic cirrhosis were r and omized to receive either colchicine 0.6 mg twice per day ( n = 274 ) or placebo ( n = 275 ) . Treatment lasted from 2 to 6 years . The primary outcome was all-cause mortality . Secondary outcomes were liver-related morbidity and mortality .  Liver biopsy was requested prior to entry and after 24 months of treatment . RESULTS Attendance at scheduled clinic visits and adherence with study medication were similar in colchicine and placebo groups . Alcohol intake was less than 1 drink per day in 69 % of patients . In an intention-to-treat analysis , all-cause mortality was similar in colchicine ( 49 % ) and placebo ( 45 % ) patients ( P = .371 ) . Mortality attributed to liver disease was 32 % in colchicine and 28 % in placebo patients ( P = .337 ) . Fewer patients receiving colchicine developed hepatorenal syndrome . In 54 patients with repeat liver biopsies after 24 or more months of treatment , cirrhosis improved to septal fibrosis in 7 patients ( 3 colchicine , 4 placebo ) and to portal fibrosis in 1 patient ( colchicine ) . CONCLUSIONS In patients with advanced alcoholic cirrhosis , colchicine does not reduce overall or liver-specific mortality . Liver histology improves to septal fibrosis in a minority of patients after 24 months of treatment , with similar rates of improvement in patients receiving placebo and colchicine . Colchicine is not recommended for patients with advanced alcoholic cirrhosis Tumor necrosis factor-alpha ( TNF-alpha ) may contribute to the progression of acute alcoholic hepatitis ( AAH ) . The aim of this study was to evaluate the efficacy of an association of infliximab and prednisolone at reducing the 2-month mortality rate among patients with severe AAH . Patients with severe AAH ( Maddrey score > /=32 ) were r and omly assigned to group A receiving intravenous infusions of infliximab ( 10 mg/kg ) in weeks 0 , 2 , and 4 ; or group B receiving a placebo at the same times . All patients received prednisolone ( 40 mg/day ) for 28 days . Blood neutrophil functional capacities were monitored over 28 days . After r and omization of 36 patients , seven patients from group A and three from group B died within 2 months . The probability of being dead at 2 months was higher ( not significant [ NS ] ) in group A ( 39 % + /- 11 % ) than in group B ( 18 % + /- 9 % ) . The study was stopped by the follow-up committee and the sponsor ( Assistance Publique-Hôpitaux de Paris ) . The frequency of severe infections within 2 months was higher in group A than in group B ( P < .002 ) . This difference was potentially related to a significantly lower ex vivo stimulation capacity of neutrophils . There were no differences between the two groups in terms of Maddrey scores at any time point . In conclusion , three infusions of 10 mg/kg of infliximab in association with prednisolone may be harmful in patients with severe AAH because of the high prevalence of severe infections Objective : To evaluate  patient survival and allograft function and health-related quality of life ( HRQOL ) 20 years after orthotopic liver transplantation ( LT ) . Summary of Background Data : Although LT is the established treatment of choice for acute and chronic liver failure , allograft function and recipient HRQOL 20 years after LT remain undefined . Methods : We performed a prospect i ve , cross-sectional study of LT recipients surviving 20 years or more . Clinical data were review ed to identify factors associated with 20-year survival . Survivors were directly contacted and offered a survey to assess HRQOL ( SF-36 ; Liver Disease Quality of Life ) , social support , and cognition ( Neuropsychological Impairment Scale ) .  Logistic regression analysis was performed to identify clinical factors influencing HRQOL 20 years after LT . Results : Between February 1 , 1984 and December 31 , 1988 , a total of 293 patients ( 179 adults , 114 children ) received 348 LTs . Of the 293 patients , 168 ( 56 % ) survived for 20 years or more . Actuarial 20-year survival was 52 % ( patient ) and 42 % ( graft ) . Factors associated with 20-year survival included recipient age < 18 ( P = 0.01 ) , nonurgent LT ( P = 0.01 ) , no retransplantation ( 0.02 ) , female gender ( 0.03 ) , absence of biliary complications ( P = 0.04 ) , and short total ischemia time ( P = 0.05 ) . Rejection episodes were seen in a greater proportion of 20-year survivors than in nonsurvivors ( 35 % vs. 27 % ; P = 0.3 ) . Of the 168 survivors , 87 were contacted , and 68 ( 78 % ) completed the HRQOL surveys . Compared with the general population , survivors had lower physical scores ( P < 0.01 ) but comparable mental scores on the SF-36 . Overall HRQOL was significantly better in 20-year survivors than in patients with chronic liver disease , congestive heart failure , or diabetes . Clinical factors associated with improved post-LT HRQOL were younger age at LT , allograft longevity , and strong social support . More than 90 % of pediatric survivors completed high school . After LT , 34 % of pediatric recipients married , and 79 % remained married at 20 years ' follow-up . Conclusions : More than 50 % of LT recipients survive 20 years , achieve important socioeconomic milestones , and report quality of life superior to patients with liver disease or other chronic conditions . LT is a durable surgery that restores both long-term physiologic and psychologic well-being in patients with end-stage liver disease BACKGROUND & AIMS Pentoxifylline , an inhibitor of tumor necrosis factor-alpha , is given to patients with liver diseases , but its effects in patients with advanced cirrhosis are unknown . We performed a r and omized , placebo-controlled , double-blind trial of its effects in patients with cirrhosis . METHODS A total of 335 patients with cirrhosis ( Child-Pugh class C ) were assigned to groups given either pentoxifylline ( 400 mg , orally , 3 times daily ; n = 164 ) or placebo ( n = 171 ) for 6 months . The primary end point was mortality at 2 months . Secondary end points were mortality at 6 months and development of liver-related complications . RESULTS By 2 months , 28 patients in the pentoxifylline group ( 16.5 % ) and 31 in the placebo group ( 18.2 % ) had died ( P = .84 ) . At 6 months , 50 patients in the pentoxifylline group ( 30.0 % ) and 54 in the placebo group ( 31.5 % ) had died ( P = .75 ) . The proportions of patients without complications ( eg , bacterial infection , renal insufficiency , hepatic encephalopathy , or gastrointestinal hemorrhage ) were higher in the pentoxifylline group than in the placebo group at 2 months ( 78.6 % vs 63.4 % ; P = .006 ) and 6 months ( 66.8 % vs 49.7 % ; P = .002 ) . The probability of survival without complications was higher in the pentoxifylline group than in the placebo group at 2 and 6 months ( P = .04 ) . In multivariate analysis , the factors associated with death were age , the Model for End-Stage Liver Disease score , and presence of early-stage carcinoma . Treatment with pentoxifylline was the only factor associated with liver-related complications . CONCLUSIONS Although pentoxifylline does not decrease short-term mortality in patients with advanced cirrhosis , it does reduce the risk of complications Background : Prednisolone and pentoxifylline ( PTX ) have been shown to be individually useful in severe alcoholic hepatitis with Maddrey discriminant function ( MDF ) score ≥32 . Previous report suggests that PTX is probably superior to prednisolone alone . However the efficacy of PTX and prednisolone combination over PTX alone in the management of acute alcoholic hepatitis ( MDF score ≥32 ) is yet unrevealed . Aim : The present study was initiated to find out the efficacy of combined pentoxifylline and prednisolone versus PTX alone in acute alcoholic hepatitis in respect of short and intermediate term outcomes . Subjects and Methods : A total of 124 patients with severe alcoholic hepatitis ( MDF score ≥ 32 ) initially were evaluated . 62 patients who fulfilled the inclusion and exclusion criteria were r and omized and divided into 2 groups . Group 1 received PTX only , whereas Group 2 received PTX plus Prednisolone . The total duration of follow-up was 12 months . Student′s t-test , Chi-square test , the Kaplan-Meier methods were used for statistical analysis . Results : A total of 60 patients , 30 in each group were available for final analysis . In Group-1 , 6 patients expired at the end of 1 year ( 5 within 3 months and another after 3 months ) . In Group 2 , 10 patients expired at the end of 1 year ( 9 within 3 months and another after 3 months ) . Though survival probability is higher among Group 1 patients but the difference is not statistically significant . Conclusion : The combination of PTX plus Prednisolone yields no additional benefit in terms of mortality and morbidity  from that of PTX monotherapy BACKGROUND & AIMS Alcoholic hepatitis is a cause of major morbidity and mortality that lacks effective therapies . Both experimental and clinical evidence indicate that the multifunctional cytokine tumor necrosis factor-alpha ( TNF-alpha ) contributes to pathogenesis and clinical sequelae of alcoholic hepatitis . A pilot study demonstrated that the TNF-alpha-neutralizing molecule etanercept could be an effective treatment for patients with alcoholic hepatitis . METHODS Forty-eight patients with moderate to severe alcoholic hepatitis ( Model for End-Stage Liver Disease score > or = 15 ) were enrolled and r and omized to groups that were given up to 6 subcutaneous injections of either etanercept or placebo for 3 weeks . Primary study end points included mortality at 1- and 6-month time points . RESULTS There were no significant baseline differences between the placebo and etanercept groups in demographics or disease severity parameters including age , gender , and Model for End-Stage Liver Disease score . The 1-month mortality rates of patients receiving placebo and etanercept were similar on an intention-to-treat basis ( 22.7 % vs 36.4 % , respectively ; OR , 1.8 ; 95 % CI , 0.5 - 6.5 ) . The 6-month mortality rate was significantly higher in the etanercept group compared with the placebo group ( 57.7 % vs 22.7 % , respectively ; OR , 4.6 ; 95 % CI , 1.3 - 16.4 ; P = .017 ) . Rates of infectious serious adverse events were significantly higher in the etanercept group compared with the placebo group ( 34.6 % vs 9.1 % , respectively , P = .04 ) . CONCLUSIONS In patients with moderate to severe alcoholic hepatitis , etanercept was associated with a significantly higher mortality rate after 6 months , indicating that etanercept is not effective for the treatment of patients with alcoholic hepatitis The efficacy of methylprednisolone ( 1 g daily or three days ) , which is effective in reversing transplant rejection , was assessed in a r and omised controlled trial of 55 patients with severe acute alcoholic hepatitis , 34 of whom had encephalopathy . The clinical progress , frequency of bleeding and sepsis , and cause of death were similar in the treatment ( 27 patients ) and control groups ( 28 patients ) . There was no significant difference in mortality rate between the two groups : 57 % of the control group and 63 % of the treatment group died during the study . Patients ' survival depended on the presence of absence of the following features : encephalopathy , serum bilirubin concentration more than 340 micromol/l , serum creatinine concentration more than 250 micromol/l , and histological evidence of cirrhosis as well as severe acute alcoholic hepatitis Study Objective : To determine the efficacy of a corticosteroid in reducing the short‐term mortality of patients with 8evere alcoholic hepatitis STUDY OBJECTIVE To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe alcoholic hepatitis . DESIGN R and omized , double-blind , placebo-controlled multicenter trial . SETTING Four university teaching hospitals . PATIENTS We enrolled 66 patients with alcoholic hepatitis and either spontaneous hepatic encephalopathy or a discriminant function value greater than 32 , calculated using the formula : 4.6 ( prothrombin time - control time ) + serum bilirubin [ in mumol/L]/17.1 . Fifty-nine patients ( 89 % ) completed the study . Two patients withdrew from the trial . The other 64 patients were hospitalized for the duration of the trial ; however , treatment was discontinued in 5 patients because of potential drug toxicity . INTERVENTIONS Patients were r and omly assigned to receive either methylprednisolone ( 32 mg ) or placebo within 7 days of admission . Treatment was given for 28 days . The doses were then tapered over 2 weeks and discontinued . MEASUREMENTS AND MAIN RESULTS The endpoint of the study was death . Of the 31 recipients of placebo , 11 ( 35 % ) died within 28 days of r and omization compared with 2 ( 6 % ) of the 35 patients given methylprednisolone ( P = 0.006 ) . The 95 % CI for the difference in mortality was 12 % to 70 % . In the patients with spontaneous hepatic encephalopathy at entry , 9 of 19 recipients of placebo  died ( 47 % ) compared with 1 ( 7 % ) of the 14 patients given methylprednisolone ( P = 0.02 ) . The 95 % CI for the difference in mortality was 14 % to 66 % . The Cox proportional hazards regression model showed the advantage of methylprednisolone over placebo after adjustment for other potentially important prognostic variables ( P = 0.004 ) . CONCLUSIONS Methylprednisolone therapy decreases short-term mortality in patients with severe alcoholic hepatitis manifested either by spontaneous hepatic encephalopathy or a markedly elevated discriminant function value Philip Hendy review s Thursz et al. 1The r and omized double blind placebo controlled Steroids or Pentoxifylline for Alcoholic Hepatitis ( STOPAH ) trial demonstrates that pentoxifylline does not improve mortality in severe alcoholic hepatitis at 28 days or beyond . It also demonstrates that prednisolone provides a non-significant mortality benefit at 28 days which does not persist to 90 days or beyond and is associated with increased risk of infection . Alcoholic hepatitis is a syndrome characterised by jaundice and liver dysfunction in the setting of significant long-term alcohol excess . Severe disease is associated with high mortality—30 % at 1 month and 40 % at 6 months.2 , 3 Treatment consists of organ support as required , as well as steroid and or pentoxifylline ( PTX ) therapy , both of which are included in national and international management guidelines . The European Association for the Study of the Liver guidelines include steroids and , in the case of ongoing sepsis , PTX.4 BACKGROUND & AIMS Corticosteroids have been shown to significantly decrease short-term mortality in patients with severe alcoholic hepatitis . However , independent factors associated with a favorable outcome and long-term survival are unknown . The aim of this study was to examine prognostic factors and long-term survival in patients with biopsy-proven severe alcoholic hepatitis . METHODS Of 183 patients studied , 61 had been r and omized in a previous trial ; 32 of them were treated with prednisolone ( group I ) and 29 were not treated ( group II ) ; 61 were treated from the end of this r and omized trial ( group III ) ; and 61 were simulated ( group IV ) . RESULTS At 1 year , survival in group I ( 69 % ; confidence interval [ CI ] , 57%-81 % ) and group III ( 71 % ; CI , 55%-87 % ) was better than in the nontreated groups ( group II , 41 % ; CI , 23%-59 % ; P = 0.01 ) ( group IV , 50 % ; CI , 37%-63 % ; P = 0.05 ) . At 2 years , survival was not significantly different . Treated patients with marked liver polymorphonuclear infiltrate had better 1-year survival ( 76 % ; CI , 64%-88 % ) than the others ( 53 % ; CI , 35%-71 % ; P = 0.05 ) . Treated patients with polymorphonuclear counts of > 5500/mm3 had better 1-year survival ( 77 % ; CI , 65%-89 % ) than the others ( 40 % ; CI , 14%-66 % ; P = 0.003 ) . In the 93 treated patients , liver polymorphonuclear infiltrate ( P < 0.03 ) and polymorphonuclear count ( P < 0.001 ) were independently correlated with 1-year survival . CONCLUSIONS Prednisolone reduced mortality by at least 1 year . Liver polymorphonuclear infiltrate and polymorphonuclear count were independent prognostic factors Sixty-four patients admitted with acute alcoholic hepatitis , with or without underlying cirrhosis , were r and omized regardless of encephalopathy to receive a controlled diet either alone , or supplemented orally , nasogastrically , or intravenously as necessary , with 2000 kCal and 10 g nitrogen daily . Whether this came from a conventional protein source or a branched chain amino acid enriched formulation was also r and omly determined . In the absence of renal failure , nitrogen intakes of 10 g or more daily were invariably associated with positive nitrogen balance , but complications of liver dysfunction prevented the attainment of significantly more positive balance in the supplemented groups than in controls . Neither in the series as a whole , nor in any identifiable subgroup of patients , was mortality affected by treatment . Changes in prothrombin time and in measured nutritional parameters during the study did not differ between supplemented and control groups , and the observed changes in midarm muscle circumference appeared to reflect changes in degree of fluid retention . Neither enteral nor parenteral branched chain amino acids showed any consistent effect upon encephalopathy The aim of our multicenter study was to assess the efficacy of ursodeoxycholic acid ( UDCA ) on the survival of patients with alcohol‐induced cirrhosis and jaundice . We included patients with histologically proven alcohol‐induced cirrhosis and serum bilirubin > 50 μmol/L. After r and omization , patients received either UDCA ( 13‐15 mg/kg/d ) or a placebo for 6 months . Two hundred twenty‐six patients ( 113 in each group ) were included in 24 centers . There were 139 men and 87 women , mean age of 50.3 years . Seventy‐four percent had associated alcohol‐induced hepatitis , and 24 % received a corticosteroid therapy . At inclusion , the 2 groups were comparable for the main clinical and biologic parameters , but serum bilirubin was higher in the UDCA group than in the placebo group ( 163 μmol/L vs. 145 μmol/L , P < .03 ) . The percentage of patients lost at follow‐up or who resumed their alcoholism during the study was comparable in the 2 groups . During the study , 55 patients died , 35 in the UDCA group and 20 in the placebo group . In the intention to treat analysis , the probability of survival at 6 months ( Kaplan‐Meier method ) was lower in the UDCA than in the P group ( 69 % vs. 82 % , respectively ; P = .04 , log‐rank test ) . After adjustment on the bilirubin level at entry ( Cox model ) , the independent predictive value of the treatment group did not reach the statistical level ( RR = 1.64 , CI 0.85‐2.85 ; P = .077 ) . In conclusion , UDCA administered at the dose recommended in primary biliary cirrhosis has no beneficial effect on the 6‐month survival of patients with severe alcohol‐induced cirrhosis . An inappropriate dosage of UDCA can not be excluded as an explanation for the lack of therapeutic benefit In a prospect i ve double-blind study , 27 patients with alcoholic hepatitis were r and omized for 6-methylprednisolone ( 12 patients ) or placebo treatment ( 15 patients ) . The mortality was 50 % among steroid treated patients and 47 % in the control group ( P less than .05 ) . The role of liver biopsy feasibility at selection is emphasized since the mortality in this group was 10 % as opposed to 71 % when the procedure was contraindicated ( P less than .01 ) . Complications in the steroid-treated subjects were similar quantitatively and qualitatively to those observed in the control series The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating BACKGROUND Mortality among patients with severe acute alcoholic hepatitis is high , even among those treated with glucocorticoids . We investigated whether combination therapy with glucocorticoids plus N-acetylcysteine would improve survival . METHODS We r and omly assigned 174 patients to receive prednisolone plus N-acetylcysteine ( 85 patients ) or only prednisolone ( 89 patients ) . All patients received 4 weeks of prednisolone . The prednisolone-N-acetylcysteine group received intravenous N-acetylcysteine on day 1 ( at a dose of 150 , 50 , and 100 mg per kilogram of body weight in 250 , 500 , and 1000 ml of 5 % glucose solution over a period of 30 minutes , 4 hours , and 16 hours , respectively ) and on days 2 through 5 ( 100 mg per kilogram per day in 1000 ml of 5 % glucose solution ) . The prednisolone-only group received an infusion in 1000 ml of 5 % glucose solution per day on days 1 through 5 . The primary outcome was 6-month survival . Secondary outcomes included survival at 1 and 3 months , hepatitis complications , adverse events related to N-acetylcysteine use , and changes in bilirubin levels on days 7 and 14 . RESULTS Mortality was not significantly lower in the prednisolone-N-acetylcysteine group than in the prednisolone-only group at 6 months ( 27 % vs. 38 % , P = 0.07 ) . Mortality was significantly lower at 1 month ( 8 % vs. 24 % , P = 0.006 ) but not at 3 months ( 22 % vs. 34 % , P = 0.06 ) . Death due to the hepatorenal syndrome was less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group at 6 months ( 9 % vs. 22 % , P = 0.02 ) . In a multivariate analysis , factors associated with 6-month survival were a younger age ( P<0.001 ) , a shorter prothrombin time ( P<0.001 ) , a lower level of bilirubin at baseline ( P<0.001 ) , and a decrease in bilirubin on day 14 ( P<0.001 ) . Infections were less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group ( P = 0.001 ) ; other side effects were similar in the two groups . CONCLUSIONS Although combination therapy with prednisolone plus N-acetylcysteine increased 1-month survival among patients with severe acute alcoholic hepatitis , 6-month survival , the primary outcome , was not improved . ( Funded by Programme Hospitalier de Recherche Clinique ; AAH-NAC Clinical Trials.gov number , NCT00863785 . ) Steroids are recommended in severe alcohol-induced hepatitis , but some data suggest that artificial nutrition could also be effective . We conducted a r and omized trial comparing the short- and long-term effects of total enteral nutrition or steroids in these patients . A total of 71 patients ( 80 % cirrhotic ) were r and omized to receive 40 mg/d prednisolone ( n = 36 ) or enteral tube feeding ( 2,000 kcal/d ) for 28 days ( n = 35 ) , and were followed for 1 year or until death . Side effects of treatment occurred in 5 patients on steroids and 10 on enteral nutrition ( not significant ) . Eight enterally fed patients were prematurely withdrawn from the trial . Mortality during treatment was similar in both groups ( 9 of 36 vs. 11 of 35 , intention-to-treat ) but occurred earlier with enteral feeding ( median 7 vs. 23 days ; P = .025 ) . Mortality during follow-up was higher with steroids ( 10 of 27 vs. 2 of 24 intention-to-treat ; P = . 04 ) . Seven steroid patients died within the first 1.5 months of follow-up . In contrast to total enteral nutrition ( TEN ) , infections accounted for 9 of 10 follow-up deaths in the steroid group . In conclusion , enteral feeding does not seem to be worse than steroids in the short-term treatment of severe alcohol-induced hepatitis , although death occurs earlier with enteral nutrition . However , steroid therapy is associated with a higher mortality rate in the immediate weeks after treatment , mainly because of infections . A possible synergistic effect of both treatments should be investigated Liv.52 , a hepatoprotective agent of herbal origin , is used empirically for the treatment of alcoholic liver disease in Sri Lanka . We conducted a controlled trial to assess the efficacy of Liv.52 in patients with alcoholic liver disease . Patients with evidence of alcoholic liver disease attending outpatient clinics were included in a prospect i ve , double blind , r and omized , placebo controlled trial . During the trial period , 80 patients who fulfilled inclusion criteria were r and omly assigned Liv.52 ( cases ; n = 40 ) or placebo ( controls ) the recommended dose of three capsules twice daily for 6 months . All patients underwent clinical examination ( for which a clinical score was computed ) , and laboratory investigations for routine  blood chemistry and liver function  before commencement of therapy ( baseline ) . Thereafter , clinical assessment s were done monthly for 6 months , while laboratory investigations were done after 1 and 6 months of therapy . There was no significant difference in the age composition , alcohol intake and baseline liver function between the two groups . The two- sample t-test was used to analyze data obtained after 1 and 6 months of therapy against baseline values . There was no significant difference in clinical outcome and liver chemistry between the two groups at any time point . There were no reports of adverse effects attributable to the drug . Our results suggest that Liv.52 may not be useful in the management of patients with alcohol induced liver disease 35 consecutive patients with alcoholic hepatitis were r and omly allocated to control ( 18 patients ) and study ( 17 patients ) groups . All patients were offered a 3000 kcal 100 g protein diet and were studied for 28 days . The study group received 70 - 85 g of intravenous aminoacids daily in the form of ' Aminosyn ' or ' Travasol ' . Both groups had similar clinical and biochemical features at the time of r and omisation . Ascites and encephalopathy tended to improve more in the study group . Serum concentrations of bilirubin ( p < 0.01 ) and albumin ( p < 0.025 ) improved in the study but not in the control group . 4 patients died in the control group , but none died in the study group . Intravenous therapy with aminoacid for 4 weeks seemed to be associated with lower mortality rate ( p < 0.02 ) and improved serum bilirubin and albumin concentrations in patients with alcoholic hepatitis Abstract A prospect i ve , double-blind controlled pilot study in 20 subjects of the efficacy of glucocorticosteroids in the treatment of severe , life-threatening , alcoholic hepatitis failed to demons A double-blind , placebo-controlled multicenter trial was conducted to determine the efficacy of oral testosterone treatment ( 200 mg three times daily ) in men with alcoholic cirrhosis . By skewed r and omization ( 3:2 ) , 134 patients received testosterone and 87 placebo .  Patients were followed from 8 to 62 months ( median = 28 months ) . In the testosterone group , 33 patients died ( 25 % ; 95 % confidence limits = 18 to 33 % ) as compared to 18 ( 21 % ; 95 % confidence limits = 13 to 31 % ) in the placebo group . Taking age and significant prognostic variables into consideration , this corresponds with a relative mortality risk of 1.17 ( 95 % confidence limits = 0.65 to 2.15 ) in the testosterone group vs. the placebo group . Testosterone treatment did not significantly affect liver biochemistry , prevalence of complications to cirrhosis or causes of death . Patients treated with testosterone developed significantly ( p less than 0.05 ) higher serum testosterone and blood hemoglobin concentrations and significantly ( p less than 0.05 ) lower plasma IgM concentrations as compared to the placebo group . The prevalence of gynecomastia decreased significantly ( p less than 0.05 ) in the testosterone group as compared to the placebo group . We conclude that oral testosterone treatment has no beneficial effect on survival and liver biochemistry in men with alcoholic cirrhosis , and adverse effects can not be excluded In a prospect i ve , r and omized , double-blind study of prednisolone therapy of acute alcoholic hepatitis , 39 % of the total group of 28 patients died . Mortality and cumulative survival were similar in steroid- and placebo-treated patients . After 14 days of therapy , the serum albumin concentration and white blood count were significantly higher in the steroid group , but all other parameters were similar . An increased risk of fungal infection appeared to be associated with steroid therapy BACKGROUND / AIMS The aim of this study is to evaluate the tolerance and effects of infliximab combined with steroids in severe alcoholic hepatitis ( AH ) . METHODS Twenty patients with biopsy-proven severe AH ( Maddrey 's score>32 ) received prednisone 40 mg/day for 28 days and either infliximab 5mg/kg IV ( group A ) or placebo ( group B ) at day 0 . Histology , plasma interleukin-6 ( IL-6 ) and interleukin-8 ( IL-8 ) were measured at baseline and at day 10 . RESULTS Infliximab was well tolerated . Histology showed no significant changes . At day 28 , Maddrey 's score significantly improved in group A ( 39 ( 32 - 53 ) to 12 ( 7 - 52 ) , P<0.05 vs. baseline ) but not in group B ( 44 ( 33 - 50 ) to 22 ( 2 - 59 ) , P = NS ) . At day 10 , IL-6 and IL-8 decreased in group A ( 25 pg/ml ( 10 - 85 pg/ml ) to 4.5 pg/ml ( 2 - 25 pg/ml ) ; 301 pg/ml ( 107 - 1207 pg/ml ) to 14 6 pg/ml ( 25 - 252 pg/ml ) , P<0.01 , P<0.05 vs. baseline , respectively ) . In group B , changes were not significant ( 38 pg/ml ( 13 - 116 pg/ml ) to 16 pg/ml ( 4 - 128 ) ; 315 pg/ml ( 26 - 1698 pg/ml ) to 110 pg/ml ( 27 - 492 pg/ml ) ) . CONCLUSIONS In severe AH , infliximab was well tolerated and associated with significant improvement in Maddrey 's score at day 28 . Although the size of this study does not allow comparison between groups , these promising results should encourage larger trials assessing the effects of this therapy on survival BACKGROUND The role of silymarin in the treatment of liver cirrhosis is controversial . AIM Clinical outcome , biochemical profile and the antiperoxidative effects of silymarin MZ-80 during 6 months treatment were investigated in patients with alcoholic liver cirrhosis . METHODS Sixty consecutive patients with alcoholic liver cirrhosis were r and omized to receive either silymarin MZ-80 ( S ) ( 150 mg t.i.d . per day ) or placebo ( P ) for periods of 6 months . Erythrocyte total glutathione ( GSH ) content , platelet malondialdehyde ( MDA ) and serum amino-terminal propeptide of procollagen Type III ( PIIINP ) were determined at baseline and at the end of treatment . RESULTS Forty-nine patients completed the study ( 24 S and 25 P ) . The 2 groups were well-matched for demographic as well as baseline clinical and laboratory parameters . Silymarin increased total GSH at 6 months ( 4.5 + /- 3.4 to 5.8 + /- 4.0 micromol/g Hb ) whereas , in the placebo group , GSH remained unchanged ( 4.1 + /- 3.9 to 4.4 + /- 4.1 micromol/gHb ) ( p < 0.001 ) , and platelet-derived non-induced MDA decreased by 33 % ( p < 0.015 ) . A parallel decrease in PIIINP values was seen with silymarin ( 1.82 1.03 to 1.36 + /- 0.5 U/ml , p < 0.033 ) but not with placebo ( 1.31 + /- 0.4 to 1.27 + /- 0.6 U/ml ) . There were no concurrent changes on laboratory indices of the pathology . CONCLUSIONS Silymarin is well-tolerated and produces a small increase in glutathione and a decrease in lipid peroxidation in peripheral blood cells in patients with alcoholic liver cirrhosis . Despite these effects no changes in routine liver tests were observed during the course of therapy BACKGROUND Recent studies have shown that the renin-angiotensin system is implicated in hepatic fibrogenesis in vitro and in vivo . However , no study was done in humans with alcoholic liver disease . AIM To investigate the antifibrotic effect of angiotensin II type 1 receptor ( AT1-R ) blocking agents ( ARB ) in patients with alcoholic liver disease . METHODS The primary outcome was improvement in patients ' histological features . Eighty-five patients with compensated alcoholic liver fibrosis ( ≥ F2 ) which was confirmed by baseline liver biopsy were r and omized ( intention-to-treat ( ITT ) ) to receive either ARB , c and esartan ( 8 mg/day ) with ursodeoxycholic acid ( UDCA ) ( 600 mg/day ) ( n = 42 ) or UDCA alone ( n = 43 ) as control for 6 months and follow-up liver biopsies were conducted . RESULTS According to the Laennec fibrosis system , c and esartan showed significantly higher rates of histological improvements ( ITT , 33.3 % vs. 11.6 % , P = 0.020 ) . In addition , the fibrosis score was significantly reduced from 3.4 ± 1.4 to 3.1 ± 1.5 ( P = 0.005 ) in the c and esartan group . C and esartan also reduced the area of fibrosis and α-smooth muscle actin positive from 11.3 ± 6.0 to 8.3 ± 4.7 and 28.7 ± 10.5 to 23.9 ± 10.3 ( % ) , and the hydroxyproline levels ( μg/g liver tissue ) from 7.8 ± 2.4 to 6.3 ± 1.7 respectively ( P < 0.05 ) . In addition , the relative expression of transforming growth factor-β1(TGF-β1 ) , collagen-1 , AT1-R , tissue inhibitor of metalloproteinase 1 ( TIMP-1 ) , metalloproteinases2 ( MMP2 ) , Rac1 and p22phox by real-time RT-PCR decreased in the c and esartan group ( P < 0.05 ) . Mean arterial blood pressure in the c and esartan group decreased mildly but significantly ( P < 0.001 ) . No significant complications and side effects were observed during the present study . CONCLUSIONS Administration of ARB in compensated alcoholic liver disease induces improvement of fibrosis in histological and quantitative measurements A cooperative study was conducted to determine the efficacy of 30 days of treatment with either a glucocorticosteroid ( prednisolone ) or an anabolic steroid ( ox and rolone ) in moderate or severe alcoholic hepatitis . One hundred thirty-two patients with moderate disease and 131 with severe disease were r and omly assigned to one of three treatments : prednisolone , ox and rolone , or placebo . During the 30 days , mortality in the groups receiving steroid therapy was not significantly different from mortality in the placebo group . Thirteen per cent of the moderately ill patients and 29 per cent of the severely ill patients died . Although neither steroid improved short-term survival , ox and rolone therapy was associated with a beneficial effect on long-term survival . This was especially true in patients with moderate disease : among those who survived for one or two months after the start of treatment the conditional six-month death rate was 3.5 per cent after ox and rolone and 19 to 20 per cent after placebo ( P = 0.02 ) . No consistent long-term effect was associated with prednisolone therapy BACKGROUND / AIMS Oxidative stress is putatively involved in the pathogenesis of alcohol-induced liver injury . This trial was devised to determine whether antioxidant therapy , alone or as an adjunct to corticosteroids , improved survival in patients with acute alcoholic hepatitis . METHODS Patients with a severe alcoholic hepatitis were stratified by sex and steroid use , and then r and omized . The active group received N-acetylcysteine for one week , and vitamins A-E , biotin , selenium , zinc , manganese , copper , magnesium , folic acid and Coenzyme Q daily for 6 months . The trial was double blinded and placebo controlled . The primary end-point was mortality within 6 months . RESULTS Thirty-six ( 20 male , 16 female ; mean discriminant function ( DF ) 86.6 ) received active drug , and 34 ( 18 male , 16 female ; mean DF 76.4 ) received placebo .  180-day survival was not significantly different between patients receiving drug and placebo ( 52.8 % vs. 55.8 % , p=0.699 ) . This was not affected by stratification for steroid use or sex . The only predictors of survival in multivariate analysis were initial bilirubin ( p=0.017 ) , white cell count ( p=0.016 ) and age ( p=0.037 ) . Treatment allocation did not affect survival in multivariate analysis ( p=0.830 ) . CONCLUSIONS Antioxidant therapy , alone or in combination with corticosteroids , does not improve 6-month survival in severe alcoholic hepatitis The effect of parenteral amino acid administration on nutritional state , liver function and mortality was assessed in patients with severe alcoholic hepatitis . Twenty-eight patients received 2 l/day of a solution of dextrose ( 65 gm/L ) and amino acids ( 25.8 gm/L ) for 1 mo , whereas 26 received only the dextrose solution . All patients were allowed to eat a st and ard hospital diet . During the month in the hospital , there were six deaths in the treatment group and five deaths in the control group . Nitrogen balance improved in the treated group , but not in the control group . Creatinine-height index , triceps skin fold measurement and levels of serum albumin and prealbumin increased similarly in both groups . Serum retinol binding protein increased more in the treatment group than it did in the control group , and transferrin was increased only in the treatment group . Serum bilirubin , type III amino-terminal procollagen peptide and aminopyrine clearance improved more in the treatment group than in the control group , whereas serum AST and prothrombin time improved in the treatment group but not in the control group . Cumulative 2-yr survival rates from the day of entry into the study were 42 % and 38 % in the treatment and control groups , respectively . Patients who survived 2 yr and patients in the treatment group who died during the 2-yr follow-up had continued improvement in serum retinol binding protein , transferrin , bilirubin and prothrombin time . These parameters were unchanged in patients in the control group who died during follow-up . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND / AIMS Severe alcoholic hepatitis is associated with high morbidity and short-term mortality .  Corticosteroids are the only widely used therapy but established contraindications to treatment or the risk of serious side-effects limit their use . The perceived need for alternative treatments together with the theoretical benefits of anti-oxidant therapy triggered the design of a r and omised clinical trial comparing these treatment modalities . METHODS One hundred and one patients were r and omized into a clinical trial of corticosteroids or a novel antioxidant cocktail with a primary endpoint of 30-day mortality . RESULTS At 30 days there were 16 deaths ( 30 % ) in the corticosteroid treated group compared with 22 deaths ( 46 % ) in the antioxidant treated group ( P=0.05 ) . The odds of dying by 30 days were 2.4 greater for patients on antioxidants ( 95 % confidence interval 1.0 - 5.6 ) . A diagnosis of sepsis was made more frequently in the AO group ( P=0.05 ) , although microbiologically proven episodes of infection occurred more often in the CS group ( P<0.01 ) . The survival advantage for corticosteroid treated patients was lost at 1 year of follow-up ( P=0.43 ) . CONCLUSIONS This study has shown that corticosteroids in the form of prednisolone 30 mg daily are superior to a broad antioxidant cocktail in the treatment of severe alcoholic hepatitis Background Colchicine , an inhibitor of collagen synthesis , has been suggested as potentially beneficial in cirrhosis . Objective This long-term , r and omized , double blind , placebo controlled trial was conducted in order to evaluate the efficacy of colchicine in alcoholic cirrhosis . Methods Ambulatory patients with biopsy proven alcoholic cirrhosis , presenting from 1989 to 1997 , with no exclusion criteria ( e.g. Child – Pugh C , bilirubin > 10 mg/dl and gastrointestinal bleeding in the previous 15 days ) , were r and omized to receive orally , 5 days/week , 1 mg/day of colchicine or placebo . Main outcome measures Results were analysed on an intention to treat basis , for survival , incidence of complications , biochemical liver tests and safety . Results Twenty-nine patients received colchicine and 26 placebo ;  characteristics of both groups were similar . The median follow-up was 40.6 ( 1.4–126.3 ) months in the colchicine versus 42.4 ( 5.7–118.2 ) months in the placebo group ( NS ) . No significant side effects were reported . During follow-up , there were no significant differences in compliance and alcohol abstinence ( 86 % vs 85 % ) . Overall survival was not statistically different ( P = 0.38 ) . Cumulative 3-year survival rates were 74.9 % in the colchicine versus 91.4 % in placebo group ( NS ) . The annual incidence rate of complications was similar with colchicine or placebo : gastrointestinal bleeding , 1.5 % vs 1.2 % ; ascites , 3.7 % vs 3.7 % ; and encephalopathy , 1.0 % vs 0.9 % . The comparison of changes in biochemical parameters between groups did not show any significant difference . Conclusions Although well tolerated , colchicine does not appear to overcome the progression and natural history of long-established alcoholic cirrhosis The effect of propylthiouracil ( PTU ; 300 mg/day ) on alcoholic liver disease was evaluated in 133 patients in a short-term r and omized double-blind trial . Severity of the disease was assessed by a composite clinical and laboratory index ( CCLI ) . A normalization rate ( NR ) representing the rate of improvement in CCLI was calculated . Patients with alcoholic hepatitis , with and without cirrhosis , showed a significantly higher NR on PTU ( 43.6 + /- 4.6 ) than on placebo ( 19.8 + /- 3.3 ; P less than 0.001 ) . A similar effect was observed in patients with abnormal prothrombin ( no biopsy ) :  NR was 32.9 + /- 6.9 on PTU and 2.6 + /- 3.7 on placebo ( P less than 0.005 ) . The effect of PTU on each clinical and laboratory component of the CCLI was also compared in these two groups . In 38 patients with alcoholic hepatitis and in 25 with abnormal prothrombin , those on PTU showed a greater improvement in 15 of 15 items ( P less than 0.001 ) and 14 of 15 ( P less than 0.01 ) , respectively . When patients were divided according to the severity of the disease into those in the lower and upper halves of the CCLI range ( 81 and 52 patients , respectively ) , PTU was shown to have a significant effect only in the latter : The NR was 41.4 + /- 3.8 on PTU and 22.5 + /- 4.2 on placebo ( P less than 0.005 ) . PTU was ineffective in patients with inactive cirrhosis Severe alcoholic hepatitis is still a therapeutic challenge . It has been recently advocated that a 3-wk infusion with insulin and glucagon reduces its short-term mortality rate . A multicenter , r and omized , single-blind , sequential trial was design ed to compare this treatment with placebo . The triangular boundary was defined with alpha = 0.05 , beta = 0.10 and estimated survival at 4 wk of 50 % with placebo , 75 % with treatment . Patients with biopsy-proven severe alcoholic hepatitis ( presence of one or more of three criteria : encephalopathy , prothrombin activity less than or equal to 50 % , bilirubinemia greater than or equal to 100 mumol/L ) were r and omized into two groups ; one treatment group received an infusion ( 12 hr/day ) of an association of insulin ( 30 IU ) and glucagon ( 3 mg ) , and a control group received an infusion of glucose . Treatments were administered during a 3-wk period , and the mortality rate was noted at 4 wk . The decision to discontinue the trial was reached on the basis of results from the first 44 patients . Overall results were assessed in the 72 patients included at the time of this decision ( treatment group : n = 37 ; control group : n = 35 ) . Fifty-three patients had cirrhosis . No significant differences were noted between the two groups at inclusion on the basis of clinical , laboratory and histological criteria . The mortality rate was not significantly different in the two groups ; 10 patients ( 27 % ) in the treatment group and 5 patients ( 14 % ) in the control group died . Causes of death were similar in the two groups and consisted primarily of gastrointestinal hemorrhage , hepatic failure and infectious events . ( ABSTRACT TRUNCATED AT 250 WORDS A double-blind prospect i ve controlled trial of d-penicillamine in 40 patients with acute alcoholic liver disease revealed no improvement in survival or liver function tests in the experimental group . Nevertheless , greater reduction in fibrosis and hepatocellular injury was suggested in penicillamine-treated biopsied patients ; this observation remains tentative and preliminary , however , because of the potential for sampling error BACKGROUND Alcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use . The short-term mortality among patients with severe disease exceeds 30 % . Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis , but uncertainty about their benefit persists . METHODS We conducted a multicenter , double-blind , r and omized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline . The primary end point was mortality at 28 days . Secondary end points included death or liver transplantation at 90 days and at 1 year . Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were r and omly assigned to one of four groups : a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo , a group that received prednisolone and a pentoxifylline-matched placebo , a group that received pentoxifylline and a prednisolone-matched placebo , or a group that received both prednisolone and pentoxifylline . RESULTS A total of 1103 patients underwent r and omization , and data from 1053 were available for the primary end-point analysis . Mortality at 28 days was 17 % ( 45 of 269 patients ) in the placebo-placebo group , 14 % ( 38 of 266 patients ) in the prednisolone-placebo group , 19 % ( 50 of 258 patients ) in the pentoxifylline-placebo group , and 13 % ( 35 of 260 patients ) in the prednisolone-pentoxifylline group . The odds ratio for 28-day mortality with pentoxifylline was 1.07 ( 95 % confidence interval [ CI ] , 0.77 to 1.49 ; P=0.69 ) , and that with prednisolone was 0.72 ( 95 % CI , 0.52 to 1.01 ; P=0.06 ) . At 90 days and at 1 year , there were no significant between-group differences . Serious infections occurred in 13 % of the patients treated with prednisolone versus 7 % of those who did not receive prednisolone ( P=0.002 ) . CONCLUSIONS Pentoxifylline did not improve survival in patients with alcoholic hepatitis .  Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year . ( Funded by the National Institute for Health Research Health Technology Assessment program ; STOPAH EudraCT number , 2009 - 013897 - 42 , and Current Controlled Trials number , IS RCT N88782125 ) UNLABELLED Liver failure is the major cause of death in alcoholic steatohepatitis ( ASH ) . In experimental hepatitis , granulocyte-colony stimulating factor ( G-CSF ) mobilizes hematopoietic stem cells , induces liver regeneration , and improves survival . We studied the short-term effects of G-CSF on CD34 + stem cell mobilization , liver cell proliferation , and liver function in patients with ASH . Twenty-four patients ( mean age 54 years ) with alcoholic cirrhosis [ Child-Turcotte-Pugh score 10 ( 7 - 12 ) ] and concomitant biopsy-proven ASH [ Maddrey score 36 ( 21 - 60 ) ] were r and omized to st and ard care associated with 5 days of G-CSF  ( 10 microg/kg/day , group A , n = 13 ) or  st and ard care alone  ( group B , n = 11 ) . Serial measurement of CD34 + cells , liver tests , cytokines [ hepatocyte growth factor ( HGF ) ; tumor necrosis factor alpha ; tumor necrosis factor-R1 ; interleukin-6 ; alfa-fetoprotein ] , and (13)C-aminopyrine breath tests were performed . Proliferating hepatic progenitor cells [ HPC ; double immunostaining ( Ki67/cytokeratin 7 ) ] , histology , and neutrophils were assessed on baseline and day 7 biopsies . Abstinent alcoholic patients with cirrhosis served as controls for immunohistochemistry .  G-CSF  was well tolerated . At day 7 , both CD34 + cells ( + 747 % versus -6 % , P < 0.003 ) , and HGF ( + 212 % versus -7 % , P < 0.03 ) increased in group A but not in group B. Cytokines and aminopyrine breath test changes were similar between groups . On repeat biopsy , a > 50 % increase in proliferating HPC was more frequent in group A than in group B ( 11 versus 2 , P < 0.003 ) . Changes in Ki67+/cytokeratin 7 + cells correlated with changes in CD34 + cells ( r = 0.65 , P < 0.03 ) . Neutrophils and histological changes were similar in both groups . CONCLUSION G-CSF mobilizes CD34 + cells , increases HGF , and induces HPC to proliferate within 7 days of administration . Larger trials would be required to determine whether these changes translate into improved liver function BACKGROUND & AIMS Severe acute alcoholic hepatitis is associated with a high mortality rate . Oxidative stress is involved in the pathogenesis of acute alcoholic hepatitis . Previous findings had also suggested that enteral nutritional support might increase survival in patients with severe acute alcoholic hepatitis . Therefore , the aim of the present study was to evaluate the efficacy of N-acetylcysteine in combination with adequate nutritional support in patients with severe acute alcoholic hepatitis . METHODS Patients with biopsy-proven acute alcoholic hepatitis and mDF ≥32 were r and omized to receive N-acetylcysteine intravenously or a placebo perfusion along with adequate nutritional support for 14 days . The primary endpoint was 6-month survival ; secondary endpoints were biological parameter evolution and infection rate . RESULTS Fifty-two patients were r and omized in the study ( 28 into the N-acetylcysteine arm , 24 into the control arm ) , and among them , five were excluded from the analysis for protocol violation . The two groups did not differ in baseline characteristics . Survival rates at 1 and 6 months in N-acetylcysteine and control groups were 70.2 vs. 83.8 % ( p=0.26 ) and 62.4 vs. 67.1 % ( p=0.60 ) , respectively . Early biological changes , documented infection rate at 1 month , and incidence of hepatorenal syndrome did not differ between the two groups . CONCLUSIONS In this study , high doses of intravenous N-acetylcysteine therapy for 14 days conferred neither survival benefits nor early biological improvement in severe acute alcoholic hepatitis patients with adequate nutritional support . However , these results must be viewed with caution , since the study suffered from a lack of power BACKGROUND & AIMS Both corticosteroid and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis . However , few studies have directly compared the efficacy of pentoxifylline and corticosteroid in patients with this condition . METHODS In this multicentre , open-labelled , r and omised non-inferiority trial , we assigned 121 patients with severe alcoholic hepatitis ( Maddrey 's discriminant function ⩾32 ) to receive either pentoxifylline ( 400 mg , 3 times daily , in 62 subjects ) or prednisolone ( 40 mg daily , in 59 subjects ) . The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone . RESULTS The 1-month survival rate of patients receiving pentoxifylline was 75.8 % ( 15 deaths ) compared with 88.1 % ( 7 deaths ) in those , taking prednisolone , for a treatment difference of 12.3 % ( 95 % confidence interval , -4.2 % to 28.7 % ; p = 0.08 ) . The 95 % confidence interval for the observed difference exceeded the predefined margin of non-inferiority ( Δ15 % ) and included zero . The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups ( 64.5 % vs. 72.9 % ; p = 0.23 ) . At 7 days , the response to therapy assessed by the Lille model was significantly lower in the prednisolone group ( n = 58 ) than in the pentoxifylline group ( n = 5 9 ) : 0.35 vs. 0.50 ( p = 0.012 ) . Hepatitis complications , including hepatorenal syndrome and side effects , such as infection and gastrointestinal bleeding , were similar in the two groups . CONCLUSIONS The findings demonstrate that the  efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone , supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes
BACKGROUND Alcohol-related liver disease is due to excessive alcohol consumption .
It includes a spectrum of liver diseases such as alcohol-related fatty liver , alcoholic hepatitis , and alcoholic cirrhosis .
Mortality associated with alcoholic hepatitis is high .
The optimal pharmacological treatment of alcoholic hepatitis and other alcohol-related liver disease remains controversial .
OBJECTIVES To assess the comparative benefits and harms of different pharmacological interventions in the management of alcohol-related liver disease through a network meta- analysis and to generate rankings of the available pharmacological interventions according to their safety and efficacy in order to identify potential treatments .
However , even in the subgroup of participants when the potential effect modifiers appeared reasonably similar across comparisons , there was evidence of inconsistency by one or more methods of assessment of inconsistency .
Therefore , we did not report the results of the network meta- analysis and reported the comparative benefits and harms of different interventions using st and ard Cochrane methodology .