非酒精性脂肪肝病的发病机制和药物研发进展

Progress in Pathogenesis and Drug Development of Nonalcoholic Fatty Liver Disease

非酒精性脂肪肝病(NAFLD)是指除酒精外其他因素导致的肝细胞内脂肪过度沉积,疾病可进一步发展为肝脂肪变性、非酒精性脂肪性肝炎、肝纤维化、肝硬化甚至肝细胞癌,其患病率逐年增加。NAFLD发病机制复杂,涉及胰岛素抵抗、细胞脂毒性、肠道菌群紊乱等。由于NAFLD复杂的发病机制,目前临床上并没有针对其治疗的一线药物,近年来研究者们主要针对胰岛素抵抗、肝细胞凋亡和炎症反应等NAFLD的关键病理环节进行了药物开发,并推进部分药物进入了Ⅲ期临床。基于此,本文将从NAFLD发病机制和临床药物研发进展两方面进行综述,旨在为该疾病的临床治疗和药物开发提供新的思路。

Nonalcoholic fatty liver disease(NAFLD)refers to excessive fat deposition in hepatocytes caused by other factors instead of alcohol,which can progress to hepatic steatosis,non-alcoholic steatohepatitis,liver fibrosis,cirrhosis and even hepatocellular carcinoma,and the morbidity is increasing year by year.The pathogenesis and pathophysiological process behind NAFLD is complex,which involve insulin resistance,lipotoxicity and intestinal flora disturbance,etc.Due to the complex pathogenesis of NAFLD,there are no first-line drugs for its treatment in clinic yet.In recent years,the development of new therapeutic drugs mainly based on the key pathological aspects of NAFLD,such as insulin resistance,hepatocyte apoptosis and inflammatory response,and some drugs have been into phaseⅢclinical trials.Thus,this article reviewed the pathogenesis and clinical drug development progress of NAFLD,so as to provide new ideas for the clinical treatment and drug development of NAFLD.