종설 : 비알코올 지방간질환의 간암 발병기전

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic condition that shows excessive fat accumulation in hepatocytes without significant alcohol intake, other liver diseases and the history of using hepatotoxic drugs. Recently, the incidence of hepatocellular carcinoma (HCC) related to NAFLD is increasing. However, the pathogenic mechanism of HCC developed from NAFLD has not been fully known. The most important pathogenic factor which affects the development of HCC is cirrhosis itself from any causes including NAFLD. To date, it is considered that NAFLD can cause HCC through insulin resistance, oxidative stress, and inflammatory process. In NAFLD, insulin resistance and its resulting hyperinsulinemia increase insulin-like growth factor-1 (IGF-1), which leads to cell growth and inhibition of apoptosis. Furthermore, hyperinsulinemia activates c-Jun amino-terminal kinase 1 (JNK1), increases free fatty acid (FFA) and reactive oxygen species (ROS), and increases the level of some inflammatory cytokines. In addition to that, various molecular biologic mechanisms such as deregulated NF-κB signaling, disorder in PI3K-AKT-PTEN pathway, defect in one-carbon metabolism, and dysfunction of microRNAs are involved in the NAFLD-mediated carcinogenesis. Finally, intestinal dysbiosis may also play a role in the pathogenesis of HCC. These pathogenic mechanisms will be discussed shortly in this review. (J Liver Cancer 2014;14:63-72)