Gual Philippe, Gilgenkrantz Hélène, Lotersztajn Sophie
Inserm-U1065, C3M, Team 8 "Hepatic complications in obesity," Nice, France.
Université Nice Côte d'Azur, Inserm, C3M, Nice, France.
Am J Physiol Cell Physiol. 2017 Mar 1;312(3):C263-C273. doi: 10.1152/ajpcell.00295.2016. Epub 2016 Nov 30.
Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis and steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (macroautophagy and chaperone-mediated autophagy) and chronic liver diseases have been reported. Autophagy may protect against steatosis and progression to steatohepatitis by limiting hepatocyte injury and reducing M1 polarization, as well as promoting liver regeneration. Its role in fibrosis and hepatocarcinogenesis is more complex. It has pro- and antifibrogenic properties depending on the hepatic cell type concerned, and beneficial and deleterious effects on hepatocarcinogenesis at initiating and late phases, respectively. This review summarizes the latest advances on the role of autophagy in different stages of fatty liver disease progression and describes its divergent and cell-specific effects during chronic liver injury.
酒精性肝病（ALD）和非酒精性脂肪性肝病（NAFLD）是肝硬化的主要病因，并增加肝细胞癌和肝脏相关死亡的风险。ALD和NAFLD具有共同的致病特征，从单纯性脂肪变性到脂肪性肝炎和脂肪性肝纤维化，这些病变可进展为肝硬化和肝细胞癌。NAFLD和ALD进展的病理生理机制复杂，仍不清楚。已有报道称自噬（巨自噬和伴侣介导的自噬）调节与慢性肝病之间存在重要联系。自噬可通过限制肝细胞损伤、减少M1极化以及促进肝再生来预防脂肪变性和进展为脂肪性肝炎。其在纤维化和肝癌发生中的作用更为复杂。根据所涉及的肝细胞类型，它具有促纤维化和抗纤维化特性，并且分别在肝癌发生的起始阶段和晚期具有有益和有害作用。本综述总结了自噬在脂肪性肝病进展不同阶段作用的最新进展，并描述了其在慢性肝损伤期间的不同及细胞特异性作用。
