Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis

Matheus Souza; Lubna Al-Sharif; Vanio L J Antunes; Daniel Q Huang; Rohit Loomba

doi:10.1097/HEP.0000000000001254

Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis

Hepatology. 2025 Dec 1;82(6):1523-1533. doi: 10.1097/HEP.0000000000001254. Epub 2025 Feb 4.

Authors

Matheus Souza¹, Lubna Al-Sharif², Vanio L J Antunes³, Daniel Q Huang^{4

5}, Rohit Loomba^{6

7}

Affiliations

¹ Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
² Department of Biomedical Sciences and Basic Clinical Skills, An-Najah National University, Nablus, Palestine.
³ Department of Medicine, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil.
⁴ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁵ Department of Medicine, Division of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore.
⁶ Department of Medicine, Division of Gastroenterology and Hepatology, MASLD Research Center, University of California at San Diego, La Jolla, California, USA.
⁷ Department of Family Medicine and Public Health, Division of Epidemiology, University of California at San Diego, San Diego, California, USA.

Abstract

Background and aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver disease. With the advent of multiple therapeutic targets in late-phase clinical drug development for MASH, there is a knowledge gap to better understand the comparative efficacy of various pharmacological agents. We conducted an updated network meta-analysis to evaluate the relative rank order of the different pharmacological agents for both fibrosis regression and MASH resolution.

Approach and results: We searched PubMed and Embase databases from January 1, 2020 to December 1, 2024, for published randomized controlled trials comparing pharmacological interventions in patients with biopsy-proven MASH. The co-primary endpoints were fibrosis improvement ≥1 stage without MASH worsening and MASH resolution without worsening fibrosis. We conducted surface under the cumulative ranking curve (SUCRA) analysis. A total of 29 randomized controlled trials (n=9324) were included. Pegozafermin, cilofexor + firsocostat, denifanstat, survodutide, obeticholic acid, tirzepatide, resmetirom, and semaglutide were significantly better than placebo in achieving fibrosis regression without worsening MASH. Pegozafermin (SUCRA: 79.92), cilofexor + firsocostat (SUCRA: 71.38), and cilofexor + selonsertib (SUCRA: 69.11) were ranked the most effective interventions. Pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, semaglutide, pioglitazone, denifanstat, semaglutide, and lanifibranor were significantly better than placebo in achieving MASH resolution without worsening fibrosis. Pegozafermin (SUCRA: 91.75), survodutide (SUCRA: 90.87), and tirzepatide (SUCRA: 84.70) were ranked the most effective interventions for achieving MASH resolution without worsening fibrosis.

Conclusions: This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design.

Keywords: NASH; drugs; metabolic dysfunction–associated steatohepatitis; network meta-analysis.

Publication types

Systematic Review
Comparative Study
Network Meta-Analysis

MeSH terms

Humans
Liver Cirrhosis* / drug therapy
Liver Cirrhosis* / etiology
Liver Cirrhosis* / pathology
Randomized Controlled Trials as Topic
Treatment Outcome