代谢相关性脂肪性肝病的治疗研究进展

Research Progress in the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease

摘要: 代谢相关脂肪性肝病(MAFLD)已成为全球最常见的慢性肝病，且患病人数仍在持续增加。该病早期表现为单纯性脂肪变性，后续可逐步进展为代谢相关脂肪性肝炎、肝纤维化、肝硬化甚至肝细胞癌。MAFLD的发病机制复杂，涉及胰岛素抵抗、脂毒性、线粒体功能障碍、炎症反应及纤维化形成等多重平行打击的交互作用。传统治疗以生活方式干预为基础，但依从性差、减重维持困难。2024年瑞美替罗(Resmetirom)获批上市，成为该领域首个靶向药物，标志着MAFLD的治疗进入新阶段。此外，GLP-1受体激动剂、SGLT-2抑制剂、PPAR激动剂等药物也展现出良好的疗效。鉴于MAFLD发病机制复杂，联合治疗将成为趋势，通过多靶点协同，既能提升治疗应答率又能减少药物副作用。未来治疗将向精准化、个体化和联合化方向发展。

Abstract: Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as the most prevalent chronic liver disease worldwide, with its affected population continuing to expand. The disease initially presents as simple steatosis, which may progressively advance to metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, cirrhosis, and even hepatocellular carcinoma. The pathogenesis of MAFLD is intricate, involving the interplay of multiple parallel hits, including insulin resistance, lipotoxicity, mitochondrial dysfunction, inflammatory responses, and fibrogenesis. Conventional treatment is founded on lifestyle intervention; however, it is constrained by poor patient compliance and difficulty in sustaining weight loss. In 2024, resmetirom received regulatory approval, becoming the first targeted therapeutic agent in this field and heralding a new era in MAFLD management. Moreover, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and peroxisome proliferator-activated receptor (PPAR) agonists have also demonstrated promising efficacy. Given the complex pathogenesis of MAFLD, combination therapy is poised to become the prevailing trend; through synergistic multi-target modulation, it can enhance therapeutic response rates while mitigating adverse drug reactions. Future treatment strategies are anticipated to evolve toward precision medicine, individualized therapy, and combination regimens.