Efficacy and Safety of Fibroblast Growth Factor 21 Analogues for Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis.

Introduction: Fibroblast growth factor 21 (FGF21) analogues may benefit patients with metabolic dysfunction-associated steatohepatitis (MASH). We aimed to compare the efficacy and safety of FGF21 analogues versus placebo for treating patients with MASH in randomized controlled trials (RCTs).

Methods: We searched PubMed, Embase, and the Cochrane Library. Primary outcomes were fibrosis improvement ≥1 stage without worsening of MASH and MASH resolution without worsening of fibrosis. Secondary outcomes were relative reduction ≥30% of the hepatic fat fraction (HFF) measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) and adverse events (AEs).

Results: We included 7 RCTs (886 patients). FGF21 analogues had a higher probability of fibrosis improvement ≥1 stage without worsening of MASH (RR: 1.54; 95% CI: 1.07, 2.22), MASH resolution without worsening of fibrosis (RR: 3.31; 95% CI: 1.80, 6.06), and reduction ≥30% in the HFF by MRI-PDFF (RR: 3.03; 95% CI: 2.12, 4.33) than placebo, without significant difference in the risk of AEs. Subgroup analyses by the stage of fibrosis showed that FGF21 analogues improved fibrosis only among patients with fibrosis stages F1-F3.

Conclusion: FGF21 analogues appear to be an effective and safe treatment option for patients with MASH, although the impact on fibrosis improvement may be limited to non-cirrhotic patients.