Zhou Da, Fan Jiangao
Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China.
Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China.
Chin Med J (Engl). 2024 Nov 20;137(22):2687-2696. doi: 10.1097/CM9.0000000000003355. Epub 2024 Oct 29.
Metabolic dysfunction-associated steatotic liver disease (MASLD), also called non-alcoholic fatty liver disease, is the most epidemic chronic liver disease worldwide. Metabolic dysfunction-associated steatohepatitis (MASH) is the critical stage of MASLD, and early diagnosis and treatment of MASH are crucial for reducing the incidence of intrahepatic and extrahepatic complications. So far, pharmacotherapeutics for the treatment of MASH are still a major challenge, because of the complexity of the pathogenesis and heterogeneity of MASH. Many agents under investigation have shown impressive therapeutic effects by targeting different key pathways, including the attenuation of steatohepatitis or fibrosis or both. It is notable that thyroid hormone receptor-β agonist, resmetirom has become the first officially approved drug for treating MASH with fibrosis. Other agents such as peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 analogs, and fibroblast growth factor 21 analogs are awaiting approval. This review focuses on the current status of drug therapy for MASH and summarizes the latest results of new medications that have completed phase 2 or 3 clinical trials, and presents the future directions and difficulties of new drug research for MASH.
代谢功能障碍相关脂肪性肝病（MASLD），也称为非酒精性脂肪性肝病，是全球最流行的慢性肝病。代谢功能障碍相关脂肪性肝炎（MASH）是MASLD的关键阶段，MASH的早期诊断和治疗对于降低肝内和肝外并发症的发生率至关重要。到目前为止，由于MASH发病机制的复杂性和异质性，用于治疗MASH的药物治疗仍然是一个重大挑战。许多正在研究的药物通过靶向不同的关键途径显示出令人印象深刻的治疗效果，包括减轻脂肪性肝炎或纤维化或两者兼有。值得注意的是，甲状腺激素受体-β激动剂瑞美替昂已成为首个正式批准用于治疗伴有纤维化的MASH的药物。其他药物，如过氧化物酶体增殖物激活受体激动剂、胰高血糖素样肽-1类似物和成纤维细胞生长因子21类似物正在等待批准。本综述重点关注MASH药物治疗的现状，总结已完成2期或3期临床试验的新药物的最新结果，并提出MASH新药研究的未来方向和困难。
