Hepatitis B virus-related hepatocellular carcinoma: Pathogenic mechanisms and novel therapeutic interventions

Abstract

Background: Infection with the hepatitis B virus (HBV) is one of most important risk factors for hepatocellular carcinoma (HCC). Indeed, HBV is considered a group 1 human carcinogen and is a highly oncogenic agent. HBV cannot be effectively controlled or completely eliminated, so chronic HBV infection is a public health challenge worldwide. Summary: It is now believed that HBV-induced HCC involves a complex interaction between multiple viral and host factors. Many factors contribute to HBV-associated HCC, including products of HBV, viral integration and mutation, and host susceptibility. This review outlines the main pathogenic mechanisms with a focus on those that suggest novel targets for the prevention and treatment of HCC. Key Message: HBV infection is an important risk factor for HCC. Understanding the interaction between viral and host factors in HBV-induced HCC will reveal potential targets for future therapies. Practical Implications: The two main therapeutic strategies consist of antiviral agents and immunotherapy-based approaches. Dendritic cell-based immunotherapy is promising for restoring the T cell-mediated antiviral immune response. Another approach is the specific expansion of the host's pool of HBV-specific T cells. Stimulation of the Toll-like receptors (TLRs), particularly TLR9, provides another means of boosting the antiviral response. Combination therapy with cytokines (interferon gamma and tumor necrosis factor alpha) plus lamivudine is more effective than these agents used alone. Therapeutic vaccines are being developed as an alternative to long-term antiviral treatment or as an adjunct.