Chronic hepatitis B virus and hepatitis C virus infections and cancer: synergy between viral and host factors

Hepatitis B virus (HBV) or hepatitis C virus (HCV) infections represent major causes of chronic liver disease and hepatocellular carcinoma. Despite inducing shared pathological events leading to oncogenic transformation, these two viruses present profound differences in their molecular features, life cycle and interplay with host factors, which significantly differentiate the prognostic and therapeutic approach to the related diseases. In the present review, we report the main mechanisms involved in the multistep process leading from HCV/HBV infection and cancer development, discussing side-by-side the analogies and differences between the two viruses. Such events can be broadly categorized into (a) direct oncogenic effects, involving integration in the host genome (in the case of HBV) and chromosomal instability, interference with oncosuppressor pathways, induction of oxidative stress, promotion of angiogenesis, epithelial–mesenchymal transition, alterations in the epigenetic asset and interaction with non-coding RNAs; and (b) indirect activities mostly mediated by host events, including chronic inflammation sustained by peculiar cytokine networks (such as interleukin-6 and lymphotoxins), metabolic dysfunctions promoted by steatohepatitis, interplay with gut microbiota and fibrotic events (mainly in HCV infection). This scenario suggests that the integrated study of viral and host factors may lead to the successful development of novel biomarkers and targets for therapy.