Scorletti Eleonora, Byrne Christopher D
Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK.
Dig Dis. 2016;34 Suppl 1:11-8. doi: 10.1159/000447276. Epub 2016 Aug 22.
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases from simple steatosis with hepatic lipid accumulation to end-stage liver disease with decompensated cirrhosis, liver failure and hepatocellular carcinoma. Recent data from the USA showed that in 2013, NAFLD was the second most frequent indication for liver transplantation behind hepatitis C. Since there are now effective treatments for hepatitis C and there is currently no licensed treatment for NAFLD, it has been predicted that over the next 10-15 years, NAFLD will replace hepatitis C as the most frequent indication for liver transplantation. Besides, increasing the risk of hepatocellular carcinoma and end-stage liver disease, it has recently become clear that NAFLD also increases risk of extrahepatic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, cardiac diseases and chronic kidney disease, to name but a few. Of each of these extrahepatic diseases, the evidence to date suggests that NAFLD is a strong risk factor for T2DM. When NAFLD occurs in combination with obesity and insulin resistance (as it frequently does), there is a marked increase in risk of incident T2DM with possible synergism occurring between liver fat accumulation, insulin resistance and obesity to further increase risk of development of T2DM. Thus, there is a reciprocal relationship between NAFLD as a risk factor for T2DM, and T2DM as a risk factor for liver disease progression in NAFLD. Moreover, recent evidence now points to the importance of perturbation of the intestinal microbiota (dysbiosis) in both T2DM and NAFLD. Consequently, there is a triangular relationship between dysbiosis and T2DM and NAFLD. This review will focus on T2DM as a key extrahepatic complication of NAFLD and will describe and discuss the triangular relationship between dysbiosis and T2DM and NAFLD and the factors and potential mechanisms underpinning this relationship.
非酒精性脂肪性肝病（NAFLD）涵盖了一系列肝脏疾病，从伴有肝脏脂质蓄积的单纯性脂肪变性到伴有失代偿性肝硬化、肝衰竭和肝细胞癌的终末期肝病。美国最近的数据显示，2013年，NAFLD是仅次于丙型肝炎的第二常见肝移植指征。由于目前丙型肝炎已有有效治疗方法，而NAFLD尚无获批的治疗方法，据预测，在未来10至15年内，NAFLD将取代丙型肝炎成为最常见的肝移植指征。此外，除了增加肝细胞癌和终末期肝病的风险外，最近还明确NAFLD还会增加肝外疾病的风险，如2型糖尿病（T2DM）、心血管疾病、心脏病和慢性肾脏病等。就这些肝外疾病中的每一种而言，迄今为止的证据表明NAFLD是T2DM 的一个重要危险因素。当NAFLD与肥胖和胰岛素抵抗同时出现时（这种情况经常发生），发生T2DM的风险会显著增加，肝脏脂肪蓄积、胰岛素抵抗和肥胖之间可能存在协同作用，进一步增加T2DM发生的风险。因此，作为T2DM危险因素的NAFLD与作为NAFLD肝病进展危险因素的T2DM之间存在相互关系。此外，最近的证据表明肠道微生物群紊乱（生态失调）在T2DM和NAFLD中都很重要。因此，生态失调与T2DM和NAFLD之间存在三角关系。本综述将重点关注T2DM作为NAFLD的一个关键肝外并发症，并将描述和讨论生态失调与T2DM和NAFLD之间的三角关系以及支撑这种关系的因素和潜在机制。
