Viral
hepatitis is one of the main causes leading to
hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following
infection may be involved. This review examines recent studies investigating the molecular mechanisms of
chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore,
hepatitis B excretory
antigen (
HBeAg) seems to be a more sensitive predictive
tumor marker exhibiting a six-fold higher relative risk in patients with positive
HBsAg and
HBeAg than those with
HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core
protein in HCV leads to hepatocellular
lipid accumulation associated with
oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in
tumor and viral cells resulting in HCC. Furthermore, high T-cell
immunoglobulin and
mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation.
Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of
reactive oxygen species with the
LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV
infection represent the most associated forms of viral
hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted
therapeutics preventing the transition from hepatic
inflammation-
fibrosis to
cancer.