Epigenetic Regulations in the Pathogenesis of HCC and the Clinical Application

Abstract

Hepatocellular carcinoma (HCC) arises from hepatocytes, which constitute 70–80% of all liver cells, and is the most frequent liver malignancy, causing more than 80% of liver cancer cases globally. HCC is rarely associated with the inheritance of familial genetic mutations [70, 129]; this explains in part why pediatric HCC cases are so rare. In fact most HCC cases are diagnosed later in life and are caused by prolonged exposure to environmental factors known to damage the liver progressively over time. Two of the major risk factors associated with the development of HCC include chronic infection with hepatitis B virus (HBV) and chronic infection with hepatitis C virus (HCV); these viruses are detectable in approximately 80% of all HCC cases [108, 123, 132]. Another contributing factor driving the development of viral HCC is the accidental consumption of aflatoxin B1 (AFB1). The toxin is found in contaminated food stores containing Aspergillus fungal species. Heavy chronic cigarette smoking has also recently emerged as a contributory factor [21]. Apart from the hepatitis viruses, the other major independent risk factor for the development of HCC is chronic over consumption of alcohol [36, 90]. Another emerging risk factor is overnutrition. Consumption of excess calories routinely can lead to nonalcoholic fatty liver disease (NAFLD). NAFLD can progress to nonalcoholic steatohepatitis (NASH) which may then further develop into HCC. HCC caused by overnutrition is also linked to obesity and diabetes [120].