Pathogenesis of NAFLD-Related Hepatocellular Carcinoma: An Up-to-Date Review

With the epidemic of obesity, type 2 diabetes mellitus, and hypertension, non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in the world. And the dysregulation of the metabolic microenvironment provides a favorable environment for the occurrence of liver cancer. In recent years, the incidence of hepatocellular carcinoma (HCC) caused by NAFLD is on the rise, especially in the United States, the UK, and France, where it is the fastest-growing cause of HCC. And due to the absence of disruptive symptoms in the early period and the lack of adequate surveillance in the population without cirrhosis, NAFLD associated-HCC is usually diagnosed at an advanced stage with larger tumors and lower cure rates, causing a substantial economic and social burden. Although many factors contribute to the occurrence and development of NAFLD-related HCC, the specific pathogenesis is still unclear. In this review, we focus on the research progress of its pathogenesis in recent years, including the role of insulin resistance, lipid accumulation and oxidative stress, gut microbiota, autophagy, the activation of the immune system, and hormonal disorders.