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),  = 0.003] and 20 mg [MD = 18.09, 95% CI (5.88, 30.31),  = 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),  = 0.007] and 20 mg [MD = -19.54, 95% CI (-33.33, -5.76),  = 0.005] groups. Significant improvement in MASH was seen in the 10 mg group [RR = 2.84, 95% CI (1.18, 6.78),  = 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.