Hepatocellular Carcinoma and Non-Alcoholic Fatty Liver Disease: From a Clinical to a Molecular Association

Hepatocellular carcinoma (HCC) is the most frequent primary neoplasm of the liver, and is the fourth most common malignancy worldwide. It is also the third leading cause of cancer-related deaths. Most cases of HCC develop on a pre-existing chronic liver disease, usually due to hepatitis C virus (HCV), hepatitis B virus (HBV), or alcohol. However, between 15% and 50% of HCC develops in the absence of a known etiology of liver disease, and different lines of evidence identify in non-alcoholic fatty liver disease (NAFLD) a possible relevant risk factor for occurrence of HCC. Insulin resistance (IR), steatosis, oxidative stress and imbalances in adipokine/cytokine interplay, the most important factors involved in NAFLD pathogenesis and progression, could also have a determinant role in liver carcinogenesis by promoting cellular growth and DNA damage. Recently, behavioral therapy and various insulin sensitizing agents have been tested in the treatment of NAFLD. A number of studies suggest that these approaches improve IR and reduce steatosis, necroinflammation and fibrosis. A potential role of these therapeutic strategies in the prevention of hepatocarcinogenesis can thus be envisaged.