title: Comparative effectiveness of pharmacological interventions for nonalcoholic steatohepatitis: A systematic review and network meta-analysis.
abstract: We performed a Bayesian network meta-analysis combining direct and indirect treatment comparisons to assess the comparative effectiveness of pharmacological agents for the treatment of nonalcoholic steatohepatitis (NASH). Through systematic literature review, we identified nine randomized, controlled trials (RCTs) including 964 patients with biopsy-proven NASH, comparing vitamin E, thiazolidinediones (TZDs), pentoxifylline, or obeticholic acid to one another or placebo. The primary outcome was improvement in fibrosis stage; secondary outcomes were improvement in ballooning degeneration, lobular inflammation, and steatosis. We reported relative risks (RRs) and 95% confidence intervals (CIs) from direct meta-analysis and 95% credible intervals (CrIs) from Bayesian network meta-analysis, and used Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to appraise quality of evidence. Moderate-quality evidence supports the use of pentoxifylline (RR, 0.26; 95% CrI: 0.05-1.00) and obeticholic acid (RR, 0.81; 95% CI: 0.70-0.95) over placebo in improving fibrosis. High-quality evidence supports the effect of vitamin E, TZDs, and obeticholic acid over placebo in improving ballooning degeneration. All four interventions seemed to have at least moderate-quality evidence over placebo to improve steatosis. Moderate-quality evidence supports that TZDs, pentoxifylline, and obeticholic acid decrease lobular inflammation. All the head-to-head comparisons were supported by very-low-quality evidence except for superiority of TZDs over vitamin E on improving steatosis and lobular inflammation, which had moderate-quality evidence.
  
  
  CONCLUSIONS
  Based on direct and network meta-analysis, pentoxifylline and obeticholic acid improve fibrosis, and vitamin E, TZDs, and obeticholic acid improve ballooning degeneration in patients with NASH. Future comparative trials of combination therapies targeting distinct histological features are warranted.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.|Division of Gastroenterology, Department of Medicine, University of California, San Diego, CA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA.
authors.forename: Rohan
authors.initials: R
authors.lastname: Khera
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Alina M
authors.initials: AM
authors.lastname: Allen
authors.affiliation: Knowledge Synthesis Unit, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.
authors.forename: M Hassan
authors.initials: MH
authors.lastname: Murad
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Diego, CA.|NAFLD Translational Research Unit, La Jolla, CA.|Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, CA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Loomba
mesh_terms: D002635:Chenodeoxycholic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D004359:Drug Therapy, Combination; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D000077205:Pioglitazone; D017594:Publication Bias; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage; D014810:Vitamin E / Q000008:administration & dosage
chemical_list: D045162:Thiazolidinediones; C464660:obeticholic acid; D000077154:Rosiglitazone; D002635:Chenodeoxycholic Acid; D014810:Vitamin E; D000077205:Pioglitazone