Molecular Pathogenesis of Hepatocellular Carcinoma

The most important risk factors for the development of human hepatocellular carcinoma (HCC) are chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), high dietary exposure to hepatic carcinogen aflatoxin B1 and alcohol abuse. Hepatitis B virus exerts its effects through integration of the viral DNA into the hepatocyte genome, or through acting as transcriptional regulator for several cellular proto-oncogenes and tumor-suppressor genes. Hepatitis C virus may affect hepatocytes via the transcriptional regulation activity of the HCV core protein or via the HCV non structural proteins NS5A, NS5B and NS2, interfering with the regulation of cell cycle and apoptosis. Environmental exposure to aflatoxin B1 can cause a specific missense mutation in codon 249 of the p53 tumor-suppressor gene. Habitual alcohol consumption leads to production of reactive oxygen species and peroxidation damage to DNA. The objective of this review is to make you acquainted with the most common risk factors and the most frequent genetic aberrations associated with the development of HCC.