He Yong, Chen Yingfen, Qian Shengying, van Der Merwe Schalk, Dhar Debanjan, Brenner David A, Tacke Frank
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
Cell Mol Immunol. 2025 Jun 10. doi: 10.1038/s41423-025-01307-5.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the most prevalent chronic liver disease worldwide, with an estimated global prevalence of approximately 30%; however, effective pharmacotherapies are still limited due to its complex pathogenesis and etiology. Therefore, a more thorough understanding of disease pathogenesis is urgently needed. An increasing number of studies suggest that MASLD and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are driven by chronic overnutrition, multiple genetic susceptibility factors, and pathogenic consequences, including hepatocyte damage and liver inflammation. Hepatic inflammation is the key event fueling the conversion from simple steatosis to steatohepatitis and fibrosis. Current therapies for MASH, including the recently approved thyroid hormone receptor-beta agonist resmetirom or the available incretin mimetics, mainly target metabolic injury to the liver but not inflammation directly. In this review, we provide an in-depth discussion of current data related to the immunological mechanisms of MASLD and summarize the effects of current and experimental therapies on immunoregulation in MASLD.
代谢功能障碍相关脂肪性肝病（MASLD），以前称为非酒精性脂肪性肝病（NAFLD），是全球最普遍的慢性肝病，全球估计患病率约为30%；然而，由于其复杂的发病机制和病因，有效的药物治疗仍然有限。因此，迫切需要更深入地了解疾病发病机制。越来越多的研究表明，MASLD及其进展形式，即代谢功能障碍相关脂肪性肝炎（MASH），是由慢性营养过剩、多种遗传易感性因素以及包括肝细胞损伤和肝脏炎症在内的致病后果驱动的。肝脏炎症是促使单纯性脂肪变性转变为脂肪性肝炎和纤维化的关键事件。目前治疗MASH的方法，包括最近批准的甲状腺激素受体β激动剂瑞美替昂或现有的肠促胰岛素类似物，主要针对肝脏的代谢损伤，而不是直接针对炎症。在这篇综述中，我们深入讨论了与MASLD免疫机制相关的当前数据，并总结了当前和实验性疗法对MASLD免疫调节的影响。
