Streba Letiția Adela Maria, Vere Cristin Constantin, Rogoveanu Ion, Streba Costin Teodor
Letiția Adela Maria Streba, Internal Medicine, Medical Semiology, University of Medicine and Pharmacy of Craiova, 200639 Craiova, Romania.
World J Gastroenterol. 2015 Apr 14;21(14):4103-10. doi: 10.3748/wjg.v21.i14.4103.
Non-alcoholic liver disease (NAFLD) defines liver abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis with or without cirrhosis development, occurring in the absence of significant alcohol consumption, use of teratogenic medication, or hereditary disorders. The association between NAFLD and metabolic syndrome is well documented and widely recognized. Obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia are the most common metabolic risk factors associated with NAFLD. Among the components of metabolic syndrome, current evidence strongly indicates obesity and diabetes as hepatocellular carcinoma (HCC) risk factors. There is also growing evidence that suggests an increased risk of HCC in NAFLD patients, even surpassing other etiologies in some high-income countries. Epidemiologic data demonstrate a parallel rise in prevalence of obesity, diabetes, NAFLD, and HCC. As obesity and its related diseases have steadily afflicted larger populations, HCC incidence is expected to increase in the future. Pathophysiologic mechanisms that underlie NAFLD development and subsequent progression to nonalcoholic steatohepatitis and cirrhosis (insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell activation, cytokine/adipocytokine signaling pathways, and genetic and environmental factors) appear to play a significant role in the development of NAFLD-related HCC. However, a comprehensive view of molecular mechanisms linking obesity, T2DM, and NAFLD-related HCC, as well as the exact sequence of molecular events, is still not understood in its entirety. Good-quality data are still necessary, and efforts should continue towards better understanding the underlying carcinogenic mechanisms of NAFLD-related HCC. In this paper, we aimed to centralize the most important links supporting these relationships, focusing on obesity, T2DM, and NAFLD-related HCC, as well as point out the major gaps in knowledge regarding the underlying molecular mechanisms behind them.
非酒精性肝病（NAFLD）指的是在无大量饮酒、使用致畸药物或遗传性疾病的情况下，出现的从单纯性脂肪变性到非酒精性脂肪性肝炎（伴或不伴有肝硬化发展）的肝脏异常情况。NAFLD与代谢综合征之间的关联已有充分记录且广为人知。肥胖、2型糖尿病（T2DM）和血脂异常是与NAFLD相关的最常见代谢风险因素。在代谢综合征的各个组成部分中，目前的证据有力地表明肥胖和糖尿病是肝细胞癌（HCC）的风险因素。也有越来越多的证据表明，NAFLD患者患HCC 的风险增加，在一些高收入国家甚至超过其他病因。流行病学数据显示肥胖、糖尿病、NAFLD和HCC的患病率呈平行上升趋势。随着肥胖及其相关疾病不断困扰着越来越多的人群，预计未来HCC的发病率将会增加。NAFLD发展以及随后进展为非酒精性脂肪性肝炎和肝硬化的病理生理机制（胰岛素抵抗和高胰岛素血症、氧化应激、肝星状细胞激活、细胞因子/脂肪细胞因子信号通路以及遗传和环境因素）似乎在NAFLD相关HCC的发生中起重要作用。然而，肥胖、T2DM和NAFLD相关HCC之间分子机制的全面观点，以及分子事件的确切顺序，仍未完全明了。高质量的数据仍然是必要的，应继续努力更好地理解NAFLD相关HCC的潜在致癌机制。在本文中，我们旨在集中阐述支持这些关系的最重要联系，重点关注肥胖、T2DM和NAFLD相关HCC，并指出关于其潜在分子机制的主要知识空白。
