Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU UK; Pinnacle Clinical Research, San Antonio, Texas, USA.
Akero Therapeutics, South San Francisco, California, USA.
J Hepatol. 2024 Sep;81(3):562-576. doi: 10.1016/j.jhep.2024.04.034. Epub 2024 May 4.
The worldwide epidemics of obesity, hypertriglyceridemia, dyslipidaemia, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH) represent a major economic burden on healthcare systems. Patients with at-risk MASH, defined as MASH with moderate or significant fibrosis, are at higher risk of comorbidity/mortality, with a significant risk of cardiovascular diseases and/or major adverse liver outcomes. Despite a high unmet medical need, there is only one drug approved for MASH. Several drug candidates have reached the phase III development stage and could lead to several potential conditional drug approvals in the coming years. Within the armamentarium of future treatment options, FGF21 analogues hold an interesting position thanks to their pleiotropic effects in addition to their significant effect on both MASH resolution and fibrosis improvement. In this review, we summarise preclinical and clinical data from FGF21 analogues for MASH and explore additional potential therapeutic indications.
全球肥胖症、高甘油三酯血症、血脂异常、2 型糖尿病和代谢相关脂肪性肝病（MASLD）/代谢相关脂肪性肝炎（MASH）的流行给医疗保健系统带来了巨大的经济负担。有风险的 MASH 患者被定义为有中度或显著纤维化的 MASH，他们患合并症/死亡率的风险更高，患心血管疾病和/或主要不良肝脏结局的风险显著增加。尽管医疗需求未得到满足，但只有一种药物被批准用于 MASH。一些候选药物已经进入 III 期开发阶段，在未来几年可能会有几种潜在的有条件药物批准。在未来的治疗选择中，成纤维细胞生长因子 21 类似物由于其除了对 MASH 缓解和纤维化改善有显著作用外，还具有多种作用，因此具有重要地位。在这篇综述中，我们总结了成纤维细胞生长因子 21 类似物治疗 MASH 的临床前和临床数据，并探讨了其他潜在的治疗适应症。
