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. 2025 May 30:16:1594091.
doi: 10.3389/fphar.2025.1594091. eCollection 2025.

A systematic review and meta-analysis of efruxifermin's efficacy in improving liver fibrosis in patients with NASH/MASH

Shuzhai Li  1 , Wangyuan Zou  2 , Yingying Zhou  1 , Wenjie Li  1 , Wei Liao  1 , Tao Li  3 , Zhiming Zhang  1
Affiliations

A systematic review and meta-analysis of efruxifermin's efficacy in improving liver fibrosis in patients with NASH/MASH

Shuzhai Li et al. Front Pharmacol. .

Abstract

Background & aims: Efruxifermin is a potential treatment for non-alcoholic steatohepatitis (NASH, now termed metabolic dysfunction-associated steatohepatitis, MASH). This study aimed to analyze the effectiveness of efruxifermin in improving liver fibrosis in patients with MASH.

Methods: Systematic searches of PubMed, Cochrane Library, and Embase databases were conducted. Randomized controlled trials evaluating the efficacy of efruxifermin compared with placebo in patients with MASH were included. The primary outcome was the proportion of patients with improvement in liver fibrosis by 1 or more stages without worsening of MASH. The secondary outcomes were non-invasive biomarkers of fibrosis and treatment-emergent adverse events (TEAEs).

Results: This meta-analysis included 4 studies with a total of 325 patients with biopsy-proven MASH and stage F1-F4 fibrosis. All studies reported histological outcomes. Compared to placebo, efruxifermin demonstrated a higher relative risk (RR) of 1.97 (95% CI 1.21 to 3.19, I 2 = 0%, P = 0.006) for achieving improvement in fibrosis by ≥ 1 stage without worsening of MASH. Furthermore, efruxifermin improved fibrosis-related non-invasive biomarkers (enhanced liver fibrosis [ELF]score, N-terminal type-III collagen pro-peptide [ProC3], and liver stiffness by FibroScan). However, efruxifermin was associated with an increased risk of adverse events compared to placebo, but this finding was not robust in sensitivity analysis.

Conclusion: Efruxifermin may be a potential therapeutic for MASH-related fibrosis, with the available data indicating seemingly favorable tolerability.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023491895, CRD42023491895.

Keywords: FGF21; MASH; efruxifermin; fibrosis; non-alcoholic; steatohepatitis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of study selection for the systematic review and meta-analysis. Initial database search (PubMed=3, Embase=16, Cochrane=18) identified 37 records. After removing 23 duplicates, 14 were screened. After excluding 1 non-original study, the full texts of 13 articles were reviewed, following which 10 were excluded (4 inaccessible data; 6 duplicates). One study added via citation searching, resulting in 4 studies included.
FIGURE 2
FIGURE 2
Risk of bias summary: review authors’ judgments about each risk of bias item for each included study. Seven domains (e.g., random sequence generation, allocation concealment, and blinding of participants) were categorized as low, unclear, or high risk, with percentage bars (0%–100%) reflecting the distribution of studies across bias categories.
FIGURE 3
FIGURE 3
Risk of bias summary: review authors’ judgments about each risk of bias item for each included study. This figure summarizes the risk of bias assessment across seven domains for four studies. Harrison (2021) and Harrison (2023a) exhibited a high risk of bias in incomplete outcome data (attrition bias), with all other domains assessed as low risk.
FIGURE 4
FIGURE 4
Results of the proportion of patients with improvement in liver fibrosis by 1 or more stages without worsening of MASH: efruxifermin vs. placebo. Pooled analysis demonstrated a significant risk ratio of 1.97 (95% CI 1.21–3.19; P = 0.006) favoring efruxifermin, with no heterogeneity observed (I 2 = 0%). CI, confidence interval; df, degrees of freedom.
FIGURE 5
FIGURE 5
Results of ELF score: efruxifermin vs. placebo. Pooled analysis demonstrated a significant risk ratio of −0.73 (95% CI -0.93 to -0.52 P < 0.00001) favoring efruxifermin, with no heterogeneity observed (I2 = 0%). CI, confidence interval; df, degrees of freedom.
FIGURE 6
FIGURE 6
Results of Pro-C3: efruxifermin vs. placebo. Pooled analysis demonstrated a significant risk ratio of −5.27 (95% CI -6.83 to -3.70; P < 0.00001) favoring efruxifermin, with no heterogeneity observed (I2 = 0%). CI, confidence interval; df, degrees of freedom.
FIGURE 7
FIGURE 7
Results of Liver stiffness by FibroScan: efruxifermin vs. placebo. Pooled analysis demonstrated a significant risk ratio of −2.85 (95% CI -4.90 to -0.80; P = 0.007) favoring efruxifermin, with no heterogeneity observed (I2 = 0%). CI, confidence interval; df, degrees of freedom.
FIGURE 8
FIGURE 8
Results of Treatment-emergent adverse events (TEAEs): efruxifermin vs. placebo. Pooled analysis demonstrated a significant risk ratio of 1.12 (95% CI 1.01–1.25; P = 0.04) favoring efruxifermin, with no heterogeneity observed (I2 = 0%). CI, confidence interval; df, degrees of freedom.
FIGURE 9
FIGURE 9
Results of Drug-related TEAEs: efruxifermin vs. placebo. Pooled analysis demonstrated a significant risk ratio of 2.28 (95% CI 1.35–3.87; P = 0.002) favoring efruxifermin, with no heterogeneity observed (I2 = 0%). CI, confidence interval; df, degrees of freedom.
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