治疗非酒精性脂肪性肝炎药物研究进展

Progress in research on drugs for treatment of nonalcoholic steatohepatitis

非酒精性脂肪性肝炎(non⁃alcoholic steatohepatitis,NASH)全球患病率约为3%~5%,生活方式干预是防治NASH的主要方法,减肥药奥利司他、抗氧化剂维生素E、胰岛素增敏剂吡格列酮等对NASH具有一定的治疗作用。近年来,针对不同机制开发的治疗NASH药物已经进入不同阶段的临床试验,如过氧化物酶体增殖激活受体α和δ的双重激动剂lanifibranor、胰高血糖素样肽⁃1受体激动剂利拉鲁肽、乙酰辅酶A羧化酶抑制剂firsocostat、甲状腺激素受体激动剂resmetirom、硬脂酰辅酶A去饱和酶⁃1抑制剂aramchol、钠⁃葡萄糖共转运蛋白2抑制剂dapagliflozin、成纤维细胞生长因子⁃21类似物efruxifermin、法尼醇X受体激动剂奥贝胆酸等。本文就NASH的治疗现状以及新药的临床研究做了系统性的总结。

Non⁃alcoholic steatohepatitis(NASH)has a global prevalnce of about 3%~5%,and lifestyle interventions are the main prevention and treatment methods of NASH.The diet pill orlistat,antioxidant vitamin E,and insulin sensitizer pioglitazone have certain therapeutic effects on NASH.In recent years,many therapeutic drugs for NASH of different mechanisms have entered clinical trials at different stages,such as the double agonist lanifibranor of peroxisome proliferator activated receptorα/δ,glucagon⁃like peptide⁃1 receptor agonist liraglutide,acetyl CoA carboxylase inhibitor firsocostat,thyroid hormone receptor agonist resmetirom,stearyl⁃CoA desaturase⁃1 inhibitor aramchol,sodium⁃glucose cotransporter 2 inhibitor dapagliflozin,fibroblast growth factor⁃21 analogue efruxifermin,Fani⁃X receptor agonist obeticholic acid,etc.In this paper,the current status of NASH treatment and clinical research of new drugs are systematically summarized.