Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Universita degli Studi di Milano, Milan, Italy.
Curr Pharm Des. 2018;24(38):4566-4573. doi: 10.2174/1381612825666190119113836.
Nonalcoholic fatty liver disease (NAFLD), now the leading cause of liver damage worldwide, is epidemiologically associated with obesity, insulin resistance and type 2 diabetes, and is a potentially progressive condition to advanced liver fibrosis and hepatocellular carcinoma. However, there is huge interindividual variability in liver disease susceptibility. Inherited factors also play an important role in determining disease predisposition. During the last years, common variants in PNPLA3, TM6SF2, MBOAT7 and GCKR have been demonstrated to predispose to the full spectrum of NAFLD pathology by facilitating hepatic fat accumulation in the presence of environmental triggers. Other variants regulating inflammation and fibrogenesis then modulate liver disease progression in those at higher risk. Evidence is also accumulating that rare variants are involved in disease predisposition. In the future, evaluation of genetic risk factors may be exploited to stratify the risk of liver-related complications of the disease, and to guide hepatocellular carcinoma surveillance and choose pharmacological therapy.
非酒精性脂肪性肝病（NAFLD），目前是全世界导致肝损伤的主要原因，在流行病学上与肥胖、胰岛素抵抗和 2 型糖尿病相关，并且是一种潜在的进展性疾病，可进展为晚期肝纤维化和肝细胞癌。然而，个体之间对肝脏疾病的易感性存在巨大差异。遗传因素在确定疾病易感性方面也起着重要作用。在过去的几年中，已经证明 PNPLA3、TM6SF2、MBOAT7 和 GCKR 中的常见变异在环境触发因素存在的情况下有利于肝脏脂肪堆积，从而导致 NAFLD 病理的全谱发生。其他调节炎症和纤维化的变异则在那些处于更高风险的人群中调节肝脏疾病的进展。越来越多的证据表明，罕见的变异也与疾病易感性有关。在未来，评估遗传风险因素可能被用于对与疾病相关的肝脏并发症的风险进行分层，并指导肝细胞癌的监测和选择药物治疗。
