代谢功能障碍相关脂肪性肝病最具潜力的新型药物选择

doi:10.16138/j.1673-6087.2026.02.02

摘要/Abstract

摘要：

代谢功能障碍相关脂肪性肝病（metabolic dysfunction-associated steatotic liver disease，MASLD）已成为全球最常见的慢性肝病之一，其进展性表型代谢功能障碍相关脂肪性肝炎（metabolic dysfunction-associated steatohepatitis，MASH）可进一步进展为肝纤维化、肝硬化甚至肝细胞癌，并与肥胖、2型糖尿病、慢性肾脏病及心血管疾病密切相关。生活方式干预仍为MASLD管理的基础，但对于伴活动性肝炎及中重度纤维化者，药物治疗已成为改变疾病进程的重要补充。近年来，选择性甲状腺激素受体β激动剂瑞美替罗和胰高血糖素样肽1受体激动剂司美格鲁肽先后获得美国食品药品监督管理局（Food and Drug Administration，FDA）批准用于成人非肝硬化、伴中重度纤维化的MASH，标志着MASH药物治疗已进入循证治疗阶段。与此同时，双重或多重肠促胰素激动剂、过氧化物酶体增殖物激活受体激动剂、成纤维细胞生长因子21类药物、肝内从头脂质生成抑制剂及遗传靶向疗法等亦显示出重要前景。未来MASLD药物治疗重点不仅在于促进MASH缓解和纤维化改善，更在于实现肝脏获益与心-肝-肾代谢风险的协同控制；而对于MASH肝硬化阶段，其特异性病理机制、有效终点设置及可推广治疗策略仍有待进一步突破。

Abstract:

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most common chronic liver diseases worldwide. Its progressive phenotype, metabolic dysfunction-associated steatohepatitis (MASH), can further progress to liver fibrosis, cirrhosis, and even hepatocellular carcinoma, and is closely associated with obesity, type 2 diabetes mellitus, chronic kidney diseases, and cardiovascular diseases. Lifestyle intervention remains the cornerstone of MASLD management. However, for patients with active hepatitis and moderate-to-severe fibrosis, pharmacotherapy has become an important complement to alter the disease course. In recent years, the selective thyroid hormone receptor-β agonist resmetirom and the glucagon-like peptide-1 receptor agonist semaglutide have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis in adults, marking the entry of MASH pharmacotherapy into the stage of evidence-based treatment. Meanwhile, dual or multi-incretin agonists, peroxisome proliferator-activated receptor agonists, fibroblast growth factor 21 analogues, inhibitors of hepatic de novo lipogenesis, and genetically targeted therapies are also showing important promise. Future pharmacotherapy for MASLD should focus not only on promoting MASH resolution and fibrosis improvement, but also on achieving hepatic benefits and integrated control of cardiovascular-renal-hepatic-metabolic risks. For the stage of MASH cirrhosis, its specific pathological mechanisms, effective endpoint setting and generalizable therapeutic strategies still require further breakthroughs.

Key words: metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis, liver fibrosis, pharmacotherapy, precision stratification

曹海霞, 周灿, 曾静. 代谢功能障碍相关脂肪性肝病最具潜力的新型药物选择[J]. 内科理论与实践, 2026, 21(02): 113-118.

CAO Haixia, ZHOU Can, ZENG Jing. The most promising novel drug options for metabolic dysfunction-associated steatotic liver disease[J]. Journal of Internal Medicine Concepts & Practice, 2026, 21(02): 113-118.

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