Efruxifermin in patients with metabolic dysfunction-associated steatohepatitis: A GRADE-assessed systematic review and meta-analysis

Abstract

BACKGROUND

Metabolic-associated steatohepatitis (MASH) is a prevalent metabolic condition affecting one-third of adults worldwide.

AIM

To evaluate the safety and efficacy of efruxifermin in patients with compensated MASH cirrhosis.

METHODS

A comprehensive search was conducted up to May 2025. Outcomes assessed included fibrosis improvement, MASH resolution, liver stiffness, and metabolic indices such as high-density lipoprotein cholesterol and homeostatic model assessment of insulin resistance. Adverse events were also analyzed. Statistical analysis was conducted using a random-effects model, with results presented as risk ratios or mean differences along with 95% confidence intervals and P-values.

RESULTS

The meta-analysis included five randomized controlled trials involving 450 patients. Efruxifermin led to significant improvement in fibrosis without worsening of MASH and MASH resolution without worsening of fibrosis (risk ratio = 3.00, 95% confidence interval: 2.05-4.38). Further, a significantly higher patients noted reduction in aspartate aminotransferase, alanine aminotransferase and homeostatic model assessment of insulin resistance levels, and increased high-density lipoprotein cholesterol. While efruxifermin was generally well-tolerated, gastrointestinal side effects such as nausea and diarrhea were more frequent in the efruxifermin group. The incidence of serious adverse events was comparable between groups.

CONCLUSION

Efruxifermin demonstrated significant efficacy in improving fibrosis, resolving MASH, and enhancing metabolic health in patients with compensated MASH cirrhosis. These findings support further investigation of efruxifermin in larger, long-term trials to confirm its therapeutic potential and safety profile.

Keywords: Efruxifermin; Metabolic-associated steatohepatitis; Metabolic dysfunction-associated steatotic liver disease; Liver fibrosis; Cholesterol; Adverse events; Patient outcomes

Core Tip: This GRADE-assessed systematic review and meta-analysis of randomized controlled trials evaluates the efficacy and safety of efruxifermin, a long-acting fibroblast growth factor 21 analogue, in patients with compensated metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis. Efruxifermin demonstrated significant improvements in liver fibrosis, MASH resolution, and metabolic parameters, with a tolerable safety profile. These findings highlight efruxifermin’s potential as a novel therapeutic option for compensated MASH cirrhosis, addressing a critical unmet need in this population.