Evaluating the Effectiveness of Pegbelfermin in MASH‐Associated Hepatic Fibrosis A Meta‐Analysis and Systematic Review of Randomized Controlled Trials

Introduction Metabolic dysfunction‐associated steatohepatitis (MASH), an advanced form of fatty liver disease, is characterized by liver inflammation and fibrosis, with an emerging interest in fibroblast growth factor (FGF)‐21 analogs, particularly pegbelfermin (PGBF). This study evaluates the efficacy and safety of PGBF in treating MASH‐associated hepatic fibrosis. Methods This meta‐analysis followed Cochrane guidelines and PRISMA standards. A comprehensive search of databases up to January 2023 focused on randomized controlled trials (RCTs) comparing PGBF to placebo for MASH. Meta‐analyses were performed with RevMan 5.4 using a random‐effects model. Results Data from 452 participants across three RCTs were analyzed. Significant improvements in adiponectin concentration were observed in both the 10 mg [MD = 18.23, 95% CI (6.35, 30.11), p = 0.003] and 20 mg [MD = 18.09, 95% CI (5.88, 30.31), p = 0.004] PGBF groups compared to placebo. Significant reductions in PRO‐C3 concentration were noted in both the 10 mg [MD = −25.50, 95% CI (−43.95, −7.05), p = 0.007] and 20 mg [MD = −19.54, 95% CI (−33.33, −5.76), p = 0.005] groups. Significant improvement in MASH was seen in the 10 mg group [RR = 2.84, 95% CI (1.18, 6.78), p = 0.02] but not in the 20 mg group. No significant improvements in liver stiffness, Modified Ishak scores, collagen proportionate area, ALT and AST levels, or treatment‐emergent adverse events (TEAEs) were observed in either dosage group. Conclusions Pegbelfermin, a promising therapy for MASH fibrosis, has demonstrated effectiveness at 10 mg, significantly improving MASH and biomarkers including adiponectin and PRO‐C3, while maintaining a generally safe profile.