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.