Mu Chenyang, Wang Sijie, Wang Zenghan, Tan Jian, Yin Haozan, Wang Yuefan, Dai Zhihui, Ding Dongyang, Yang Fu
School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China; Department of Medical Genetics, Naval Medical University, Shanghai, China.
Department of Medical Genetics, Naval Medical University, Shanghai, China.
Ann Hepatol. 2025 Jan-Jun;30(1):101774. doi: 10.1016/j.aohep.2024.101774. Epub 2024 Dec 17.
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) includes liver disease processes from simple fatty liver to nonalcoholic steatohepatitis, which may progress to liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). As the incidence of HCC derived from viral hepatitis decreases, MASLD has emerged as a significant health threat, driven by lifestyle changes and rising obesity rates among patients. The pathogenesis of MASLD is complex, involving factors such as insulin resistance, gut microbiota imbalance, and genetic and epigenetic factors. In recent years, the role of mitochondrial dysfunction in MASLD has gained significant attention, involving β-oxidation imbalance, oxidative stress increase, mitophagy defects, and mitochondrial DNA (mtDNA) mutations. This article reviews the pathophysiological mechanisms of mitochondrial dysfunction in MASLD, diagnostic methods, and potential therapeutic strategies. By synthesizing current research findings, the review aims to highlight the critical role of mitochondrial dysfunction as a target for future diagnostic and therapeutic interventions. This focus could pave the way for innovative clinical strategies, ultimately improving treatment options and patient prognosis in MASLD.
代谢功能障碍相关脂肪性肝病（MASLD）包括从单纯性脂肪肝到非酒精性脂肪性肝炎的肝脏疾病进程，后者可能进展为肝纤维化、肝硬化，甚至肝细胞癌（HCC）。随着病毒性肝炎所致HCC发病率的下降，MASLD已成为一种重大的健康威胁，这是由生活方式改变和患者肥胖率上升所驱动的。MASLD的发病机制复杂，涉及胰岛素抵抗、肠道微生物群失衡以及遗传和表观遗传因素等。近年来，线粒体功能障碍在MASLD中的作用受到了广泛关注，涉及β-氧化失衡、氧化应激增加、线粒体自噬缺陷和线粒体DNA（mtDNA）突变。本文综述了MASLD中线粒体功能障碍的病理生理机制、诊断方法及潜在治疗策略。通过综合当前的研究结果，本综述旨在强调线粒体功能障碍作为未来诊断和治疗干预靶点的关键作用。这一重点可为创新临床策略铺平道路，最终改善MASLD的治疗选择和患者预后。
