Fibroblast Growth Factor 21 Analogues Improve Fibrosis in Metabolic Dysfunction-Associated Steatohepatitis: An...

Area of Science:

• Hepatology
• Endocrinology
• Pharmacology

Background:

• Metabolic dysfunction-associated steatohepatitis (MASH) is a growing global health concern causing liver morbidity.
• While new MASH fibrosis treatments exist, further antifibrotic therapies are essential.
• Fibroblast Growth Factor 21 (FGF21) analogues, targeting lipid metabolism and insulin sensitivity, have shown potential in clinical trials.

Purpose of the Study:

• To systematically review and meta-analyze the efficacy and safety of FGF21 analogues for improving liver fibrosis in MASH patients.
• To quantify the antifibrotic effects of FGF21 analogues.
• To assess the safety profile of FGF21 analogues in MASH treatment.

Main Methods:

• Searched PubMed, Scopus, and Cochrane Library for randomized controlled trials (RCTs) of FGF21 analogues versus placebo in adults with biopsy-confirmed MASH.
• Primary outcome: ≥1-stage histological fibrosis improvement without MASH worsening.
• Secondary outcomes: changes in hepatic fat, liver enzymes, and metabolic parameters; data pooled using random-effects models.

Main Results:

• 10 RCTs (1113 patients) were included; FGF21 analogues significantly increased fibrosis improvement (RR: 2.25, CI: 1.25-4.03) versus placebo.
• FGF21 analogues demonstrated greater reductions in hepatic fat, liver stiffness, and fibrosis biomarkers.
• Adverse events were similar between groups; gastrointestinal issues (nausea, diarrhea) and injection site reactions were mild and manageable.

Conclusions:

• FGF21 analogue therapy is linked to significant histological fibrosis improvement in MASH patients.
• The treatment appears well-tolerated, suggesting potential as a valuable MASH pharmacotherapy.
• Larger trials and long-term data are necessary to confirm these findings.