Comparative effectiveness of pharmacological interventions... : Hepatology (original) (raw)

Steatohepatitis/Metabolic Liver Disease

Comparative effectiveness of pharmacological interventions for nonalcoholic steatohepatitis: A systematic review and network meta‐analysis

Singh, Siddharth1,2; Khera, Rohan3; Allen, Alina M.1; Murad, M. Hassan4; Loomba, Rohit*,2,5,6

1Division of Gastroenterology and HepatologyDepartment of Internal Medicine, Mayo ClinicRochesterMN

2Division of Gastroenterology, Department of MedicineUniversity of CaliforniaSan DiegoCA

3Department of Internal MedicineUniversity of Iowa Hospitals and ClinicsIowa CityIA

4Knowledge Synthesis Unit, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo ClinicRochesterMN

5NAFLD Translational Research UnitLa JollaCA

6Division of EpidemiologyDepartment of Family and Preventive Medicine, University of CaliforniaSan DiegoCA

*Address reprint requests to: Rohit Loomba, M.D., M.H.Sc., Division of Gastroenterology, Department of Medicine, and Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego School of Medicine, UC 303, MC‐0063, 9500 Gilman Drive, La Jolla, CA 92093. E‐mail: [email protected]; fax: 858‐534‐3338.

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. (Hepatology 2015;62:1417–1432)