BACKGROUND AND AIMS: The burden of metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis is rapidly rising globally. There are several therapeutic agents under clinical development for the treatment of cirrhosis due to MASH; however, their relative efficacy has not been systematically assessed. This systematic review and network meta-analysis was performed to compare the histological efficacy of available therapeutic agents for compensated MASH cirrhosis.
METHODS: PubMed and Cochrane Library databases were searched from inception to May 25, 2025, for randomised controlled trials (RCTs) evaluating pharmacological treatments in patients with biopsy-proven compensated MASH cirrhosis (F4c). The primary endpoint was fibrosis regression of at least one stage without MASH worsening, and the secondary endpoint was MASH resolution. Treatment comparisons were conducted via network meta-analysis, and ranking probabilities were estimated using the surface under the cumulative ranking (SUCRA) curve analysis.
RESULTS: Nine RCTs with 3266 participants met the eligibility criteria. Efruxifermin was the only intervention significantly superior to placebo for ≥ 1-stage fibrosis improvement without worsening of MASH. The highest-ranked interventions for fibrosis improvement were efruxifermin (SUCRA: 77.44), cilofexor + firsocostat (SUCRA: 72.38) and aldafermin (SUCRA: 71.27). For MASH resolution, efruxifermin, semaglutide + cilofexor + firsocostat and semaglutide were significantly superior to placebo. Efruxifermin (SUCRA: 81.38), semaglutide + cilofexor + firsocostat (SUCRA: 74.07) and semaglutide (SUCRA: 63.88) had the highest probability of ranking best for MASH resolution.
CONCLUSION: This network meta-analysis provides relative rank-order estimates of the histological efficacy of available pharmacological therapies for compensated MASH cirrhosis. These data may have implications for the design of future clinical trials.
