Chronic hepatitis C virus infection and pathogenesis of hepatocellular carcinoma

Abstract

Hepatitis C virus (HCV) infection is one of the major causes of advanced liver disease and hepatocellular carcinoma (HCC) worldwide. While the knowledge about the molecular virology of HCV infection has markedly advanced, the molecular mechanisms of disease progression leading to fibrosis, cirrhosis and HCC are still unclear. Accumulating experimental and clinical studies indicate that HCV may drive hepatocarcinogenesis directly via its proteins or transcripts, and/or indirectly through induction of chronic liver inflammation. Despite the possibility to eradicate HCV infection through direct-acting antiviral treatment, the risk of HCC persists although specific biomarkers to estimate this risk are still missing. Thus, a better understanding of HCV-induced HCC and more physiological liver disease models are required to prevent cancer development.

Figure 1. HCV RNA and proteins perturb hepatocellular homeostasis by driving major cancer hallmarks

The diagram (adapted from [8]) shows the HCV-host interactions and signaling upon viral infection that contribute to cellular transformation and development of HCC. The red arrows indicate HCV RNA and proteins exerting a direct effect on a specific hallmark. Black arrows link specific hallmarks to examples of mechanisms of HCV-driven HCC, which were observed in both clinical and in vivo experimental models. Regarding the tumor promoting inflammation hallmark (in orange in the diagram), this is activated by the pathogen recognition receptors that sense HCV infection. Dotted lines indicate examples of inflammation-driven carcinogenesis. sRNA, small RNA.