Dolovitsch de Oliveira Fabiana, Khalil Samira Mohamad, Sato Emmily Daiane Buarque de Santana, de Souza Matheus Henrique Gonçalves, Meine Gilmara Coelho
Department of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil,
Department of Medicine, Universidad de Buenos Aires, Buenos Aires, Argentina.
Ann Nutr Metab. 2025;81(1):51-60. doi: 10.1159/000541583. Epub 2024 Oct 3.
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).
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).
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.
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.
成纤维细胞生长因子21（FGF21）类似物可能对代谢功能障碍相关脂肪性肝炎（MASH）患者有益。我们旨在比较在随机对照试验（RCT）中FGF21类似物与安慰剂治疗MASH患者的疗效和安全性。
我们检索了PubMed、Embase和Cochrane图书馆。主要结局为纤维化改善≥1期且MASH无恶化，以及MASH缓解且纤维化无恶化。次要结局为通过磁共振成像衍生的质子密度脂肪分数（MRI-PDFF）测量的肝脂肪分数（HFF）相对降低≥30%和不良事件（AE）。
我们纳入了7项RCT（886例患者）。与安慰剂相比，FGF21类似物在纤维化改善≥1期且MASH无恶化（RR：1.54；95%CI：1.07，2.22）、MASH缓解且纤维化无恶化（RR：3.31；95%CI：1.80，6.06）以及通过MRI-PDFF使HFF降低≥30%（RR：3.03；95%CI：2.12，4.33）方面的概率更高，而AE风险无显著差异。按纤维化阶段进行的亚组分析表明，FGF21类似物仅在纤维化1 - 3期的患者中改善了纤维化。
FGF21类似物似乎是MASH患者有效且安全的治疗选择，尽管对纤维化改善的影响可能仅限于非肝硬化患者。
