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

source extracted confidence: high 2026-04-09
#humans #liver-cirrhosis #randomized-controlled-trials-as-topic #treatment-outcome

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

Souza et al., 2025 | Hepatology | Systematic Review

Citation

Souza Matheus, Al-Sharif Lubna, ... Loomba Rohit. Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis. Hepatology. 2025-Dec-01;82(6):1523-1533. doi:10.1097/HEP.0000000000001254

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.

Key Findings

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 +

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population biopsy
Sample Size 9324
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Liver Cirrhosis
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review, Comparative Study, Network Meta-Analysis
  • Vertical: vitamin-e

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09