Efficacy of efruxifermin in improving liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis/nonalcoholic steatohepatitis: a systematic review and meta-analysis of randomized controlled trials.

Abstract

In addition to demonstrating a predominant association with liver morbidity and mortality, metabolic dysfunction-associated steatohepatitis (MASH) constitutes a leading cause of liver transplantation. Efruxifermin, a bivalently linked fibroblast growth factor 21 analogue, inhibits fibrosis and protects hepatocytes from cellular distress. Although phase 2 clinical trials have investigated its histological and biochemical effects on the improvement of fibrosis, the results lack a pooled synthesis. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials to retrieve relevant articles from inception till July 2025. Data for various outcomes were extracted after computing the risk ratios with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences with 95% CIs for continuous outcomes. The quality assessment of the included randomized controlled trials (RCTs) was performed using the Cochrane Risk of Bias (RoB 2.0) tool. A total of four RCTs were included. Efruxifermin demonstrated a higher incidence of improvement in liver fibrosis by greater than or equal to one stage without worsening of MASH (risk ratio = 1.73; 95% CI = 1.14-2.62; P = 0.01). With regards to noninvasive biomarkers of fibrosis, efruxifermin showed improvement in enhanced liver fibrosis score (mean difference = -0.59; 95% CI = -0.87 to -0.32; P < 0.0001), N-terminal type-III collagen pro-peptide (Pro-C3; mean difference = -6.38; 95% CI = -10.44 to -2.32; P = 0.002) and liver stiffness by FibroScan (mean difference = -2.66; 95% CI = -4.32 to -1.01; P = 0.002). However, it demonstrated a higher risk of treatment-emergent adverse events (risk ratio = 1.18; 95% CI = 1.01-1.38; P = 0.04) compared to placebo. Subgroup analysis stratified by efruxifermin dosages showed that treatment with 28 mg dose (risk ratio = 1.71; 95% CI = 1.08-2.72; P = 0.02) and 50 mg dose (risk ratio = 1.75; 95% CI = 1.11-2.76; P = 0.02) showed significant improvement in fibrosis by greater than or equal to one stage without worsening of MASH. Among the various pharmacologic interventions, efruxifermin combines clinically meaningful antifibrotic efficacy with systemic metabolic improvements in a balanced profile.