Liu Chang-Hai, Zeng Qing-Min, Hu Teng-Yue, Huang Yu, Song Yongfeng, Guan Haixia, Rockey Don C, Tang Hong, Li Sheyu
Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China. Laboratory of Infectious and Liver Diseases, Institute of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China. Laboratory of Infectious and Liver Diseases, Institute of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
Portal Hypertens Cirrhosis. 2025 Mar;4(1):66-78. doi: 10.1002/poh2.100. Epub 2025 Jan 22.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a rapidly increasing chronic disease worldwide, particularly among patients with type 2 diabetes. Its severe form, metabolic dysfunction-associated steatohepatitis (MASH), is also on the rise. The treatment of MASLD and MASH poses significant challenges. Thyroid hormones and their receptors (TR) agonists, especially resmetirom, have shown potential in improving metabolism and reducing liver inflammation. Thyroid hormones play a crucial role in regulating metabolism and maintaining physiological balance. However, in patients with MASLD, there is a reduced conversion of 3,3',5,5'-tetraiodo-L-thyronine (T) to biologically active 3,5,3'-triiodo-L-thyronine (T), resulting in decreased T levels and impaired hepatic TR signaling. This hormonal imbalance is associated with disrupted hepatic lipid metabolism. Resmetirom, an oral selective TR agonist that specifically targets hepatocytes, was approved by the Food and Drug Administration (FDA) in March 2024 for the treatment of moderate to severe liver fibrosis in non-cirrhotic adults with MASH. This approval was based on the results of the MAESTRO clinical program, which includes multiple-stage research designs such as the MAESTRO-NASH, MAESTRO-NAFLD-1, MAESTRO-NAFLD-OLE, and MAESTRO-NASH-OUTCOMES, aims to evaluate the efficacy and safety of resmetirom in different populations of MASH patient. Although the approval of resmetirom represents a significant milestone in the treatment of MAFLD and MASH, many questions remain regarding its long-term effectiveness and impact on clinical outcomes. Ongoing research, particularly through the MAESTRO program, holds promise for providing additional insights into the long-term management of MASLD using resmetirom and other similar medications.
代谢功能障碍相关脂肪性肝病（MASLD）是一种在全球范围内迅速增加的慢性疾病，在2型糖尿病患者中尤为常见。其严重形式，即代谢功能障碍相关脂肪性肝炎（MASH），也在上升。MASLD和MASH的治疗面临重大挑战。甲状腺激素及其受体（TR）激动剂，尤其是瑞美替昂，已显示出改善代谢和减轻肝脏炎症的潜力。甲状腺激素在调节代谢和维持生理平衡方面起着关键作用。然而，在MASLD患者中，3,3',5,5'-四碘-L-甲状腺原氨酸（T4）向生物活性3,5,3'-三碘-L-甲状腺原氨酸（T3）的转化减少，导致T3水平降低和肝脏TR信号受损。这种激素失衡与肝脏脂质代谢紊乱有关。瑞美替昂是一种口服选择性TR激动剂，专门针对肝细胞，于2024年3月获得美国食品药品监督管理局（FDA）批准，用于治疗非肝硬化成年MASH患者的中度至重度肝纤维化。该批准基于MAESTRO临床项目的结果，该项目包括多个阶段的研究设计，如MAESTRO-NASH、MAESTRO-NAFLD-1、MAESTRO-NAFLD-OLE和MAESTRO-NASH-OUTCOMES，旨在评估瑞美替昂在不同MASH患者群体中的疗效和安全性。尽管瑞美替昂的批准是MAFLD和MASH治疗中的一个重要里程碑，但其长期有效性和对临床结局的影响仍存在许多问题。正在进行的研究，特别是通过MAESTRO项目，有望为使用瑞美替昂和其他类似药物进行MASLD的长期管理提供更多见解。
