Systematic review with network meta-analysis: comparative efficacy of pharmacologic therapies for fibrosis improvement and resolution of NASH

Aliment Pharmacol Ther. 2021 Oct;54(7):880-889. doi: 10.1111/apt.16583. Epub 2021 Aug 25.


Background: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. There is a major need to understand the efficacy of different pharmacological agents for the treatment of NASH.

Aim: To assess the relative rank-order of different pharmacological interventions in fibrosis improvement and NASH resolution.

Methods: A comprehensive search of several databases was conducted by an experienced librarian. We included randomised controlled-trials (RCTs) comparing pharmacological interventions in patients with biopsy-proven NASH. The primary outcome was ≥1 stage improvement in fibrosis. The secondary outcome was NASH resolution.

Results: A total of 26 RCTs with 23 interventions met the eligibility criteria. Lanifibranor and obeticholic acid had the highest probability of being ranked the most effective intervention for achieving ≥1 stage of fibrosis improvement (SUCRA 0.78) and (SUCRA 0.77), respectively. For NASH resolution, semaglutide, liraglutide and vitamin E plus pioglitazone had the highest probability of being ranked the most effective intervention for achieving NASH resolution (SUCRA 0.89), (SUCRA 0.84) and (SUCRA 0.83), respectively. Lanifibranor, obeticholic acid, pioglitazone and vitamin E were significantly better than placebo in achieving ≥1 stage of fibrosis improvement. Conversely, semaglutide, liraglutide, vitamine E plus pioglitazone, pioglitazone, lanifibranor and obeticholic acid were significantly better than placebo in achieving NASH resolution.

Conclusion: These data provide relative rank-order efficacy of various NASH therapies in terms of their improvements in liver fibrosis and NASH resolution. Therapies that have been shown to improve NASH resolution may be combined with therapies that have an antifibrotic effect to further boost treatment response rate in future.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Systematic Review

MeSH terms

  • Biopsy
  • Humans
  • Liver Cirrhosis / drug therapy
  • Network Meta-Analysis
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Pioglitazone / therapeutic use
  • Vitamin E / therapeutic use


  • Vitamin E
  • Pioglitazone