Significance of hepatitis virus infection in the oncogenic initiation of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, and DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.

Keywords: Hepatitis B virus; Hepatitis C virus; Hepatocellular carcinoma; Oncogenicity; Viral pathogenicity.

Figure 1

Oncogenicity of hepatitis B virus and hepatitis C virus in hepatocarcinogenesis. HCV: Hepatitis C virus; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma.