Emerging metabolic risk factors in hepatocellular carcinoma and their influence on the liver microenvironment

Despite the reducing incidence of chronic hepatitis infections, an unexpected increasing incidence of hepatocellular carcinoma (HCC) has being occurred. This may be explained by the increasing number of HCCs developing on steatosis (NAFLD) and steatohepatitis (NASH), related to metabolic risk factors (i.e. diabetes mellitus type II, obesity, metabolic syndrome), which are becoming emerging risk factors for HCC. This led to a growing scientific interest on the oncogenic mechanisms underlying the transition from NAFLD to HCC. However, patients with NASH receive significantly less HCC surveillance than patients with chronic hepatitis, and no specific preventive pharmacological treatments have recommended for NASH-related HCC. This review focuses on the pathogenic role of the emerging factors involved in the transition from NAFLD/NASH to HCC, including microbiota, insulin resistance, inflammation, lipid and bile acids metabolism. It will be emphasize their impact on the liver microenvironment, the implications in clinical practice and the future directions of research.