title: Comparative Effectiveness of Pharmacological Interventions for Severe Alcoholic Hepatitis: A Systematic Review and Network Meta-analysis.
abstract: OBJECTIVE
  Severe alcoholic hepatitis (AH) has high mortality. We assessed the comparative effectiveness of pharmacological interventions for severe AH, through a network meta-analysis combining direct and indirect treatment comparisons.
  
  
  METHODS
  We conducted a systematic literature review, through February 2015, for randomized controlled trials of adults with severe AH (discriminant function ≥32 and/or hepatic encephalopathy) that compared the efficacy of active pharmacologic interventions (corticosteroids, pentoxifylline, and N-acetylcysteine [NAC], alone or in combination) with each other or placebo, in reducing short-term mortality (primary outcome) and medium-term mortality, acute kidney injury, and/or infections (secondary outcomes). We performed direct and Bayesian network meta-analysis for all treatments, and used Grading of Recommendations Assessment, Development and Evaluation criteria to appraise quality of evidence.
  
  
  RESULTS
  We included 22 randomized controlled trials (2621 patients) comparing 5 different interventions. In a direct meta-analysis, only corticosteroids decreased risk of short-term mortality. In a network meta-analysis, moderate quality evidence supported the use of corticosteroids alone (relative risk [RR], 0.54; 95% credible interval [CrI], 0.39-0.73) or in combination with pentoxifylline (RR, 0.53; 95% CrI, 0.36-0.78) or NAC (RR, 0.15; 95% CI, 0.05-0.39), to reduce short-term mortality; low quality evidence showed that pentoxifylline also decreased short-term mortality (RR, 0.70; 95% CrI, 0.50-0.97). The addition of NAC, but not pentoxifylline, to corticosteroids may be superior to corticosteroids alone for reducing short-term mortality. No treatment was effective in reducing medium-term mortality. Imprecise estimates and the small number of direct trials lowered the confidence in several comparisons.
  
  
  CONCLUSIONS
  In patients with severe AH, pentoxifylline and corticosteroids (alone and in combination with pentoxifylline or NAC) can reduce short-term mortality. No treatment decreases risk of medium-term mortality.
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, California. Electronic address: sis040@ucsd.edu.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Singh
authors.affiliation: Knowledge and Evaluation Research Unit, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
authors.affiliation: Division of Gastroenterology and Liver Diseases, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Apoorva K
authors.initials: AK
authors.lastname: Chandar
authors.affiliation: Department of Library Services, Mayo Clinic-St. Mary's Hospital Library, Rochester, Minnesota.
authors.forename: Connie M
authors.initials: CM
authors.lastname: Bongiorno
authors.affiliation: Division of Gastroenterology and Hepatology, University of Alabama, Birmingham, Alabama.
authors.forename: Ashwani K
authors.initials: AK
authors.lastname: Singal
authors.affiliation: Division of Hepatology, Imperial College, London, United Kingdom.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Atkinson
authors.affiliation: Division of Hepatology, Imperial College, London, United Kingdom.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Thursz
authors.affiliation: Division of Gastroenterology, Department of Medicine, and Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, California.
authors.forename: Rohit
authors.initials: R
authors.lastname: Loomba
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Vijay H
authors.initials: VH
authors.lastname: Shah
mesh_terms: D000111:Acetylcysteine / Q000009:adverse effects / Q000627:therapeutic use*; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D057186:Comparative Effectiveness Research; D018450:Disease Progression; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers / Q000009:adverse effects / Q000627:therapeutic use*; D006519:Hepatitis, Alcoholic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D010431:Pentoxifylline / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D016166:Free Radical Scavengers; D010431:Pentoxifylline; D000111:Acetylcysteine
keywords: Clinical Trial; GRADE; Liver Failure; Survival