TY - JOUR
T1 - Comparative effectiveness of pharmacological interventions for nonalcoholic steatohepatitis
T2 - A systematic review and network meta-analysis
AU - Singh, Siddharth
AU - Khera, Rohan
AU - Allen, Alina M.
AU - Murad, M. Hassan
AU - Loomba, Rohit
N1 - Publisher Copyright:
© 2015 by the American Association for the Study of Liver Diseases.
PY - 2015/11
Y1 - 2015/11
N2 - 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.
AB - 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.
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U2 - 10.1002/hep.27999
DO - 10.1002/hep.27999
M3 - Article
C2 - 26189925
AN - SCOPUS:84945185644
SN - 0270-9139
VL - 62
SP - 1417
EP - 1432
JO - Hepatology
JF - Hepatology
IS - 5
ER -