代谢功能障碍相关的脂肪肝炎 (MASH) - 肝硬化临床试验:经验教训和未来方向
Rashmee Patil1,2, Winston Dunn1,3, Mazen Noureddin2,4
1Pinnacle Clinical Research, San Antonio, TX, USA.
Drugs
|March 14, 2026
概括
与代谢功能障碍相关的脂肪肝肝硬化是一个日益严重的健康问题. 高风险的MASH肝硬化患者应被纳入第三期试验,以评估肝脏结果的新疗法.
科学领域:
- 肝病学和胃肠病学 肝病学和胃肠学
- 临床试验设计 临床试验设计
- 代谢疾病 代谢疾病
背景情况:
- 代谢功能障碍相关的胆固醇肝炎 (MASH) 肝硬化是一个重大的全球健康挑战,导致严重的并发症,如肝衰竭,癌症和死亡.
- 与MASH相关的肝细胞癌 (HCC) 发病率的增加增加,增加了对肝移植的需求.
- 目前针对MASH肝硬化3期试验的指导方针侧重于主要不良肝结果 (MALO),肝移植和死亡率的复合终点.
研究的目的:
- 在补偿MASH肝硬化患者的第三期临床试验中概述最佳策略.
- 确定关键的患者特征和终点,以提高试验效率和成功率.
- 讨论基于组织学改善的加速批准的可能性.
主要方法:
- 建议招募患有MASH肝硬化的高风险患者,其定义为临床显著的门性高血压 (CSPH),儿童-图尔科特-普格A状态和升高的肝硬度测量 (>6.5kPa).
- 倡导3-5年的随访和使用非侵入性标准来招募患者.
- 建议将进展为大型胃食道静脉作为终点,这可以增加每年事件率的3-5%.
主要成果:
- 在代谢性慢性疾病中,硬结局的效应大小通常在0.70-0.85.5之间.
- 在MASH肝硬化试验中的事件率在具有特定风险特征的患者中可能高出3-20%.
- 在使用efruxifermin的2b期试验中,在96周内实现了肝硬化组织学逆转 (F4回归),这表明加速批准的可能性.
结论:
- 针对MASH肝硬化的第三期试验应针对高风险人群,并利用包括主要不良肝脏结果在内的复合终点.
- 应探索增加回归率的策略,例如特定的肝硬度测量极限和血小板值.
- 目前正在进行的试验正在研究新型疗法,如survodutide,efruxifermin和resmetirom,以解决MASH肝硬化管理中的未满足需求.
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