Published online Oct 14, 2020. doi: 10.3748/wjg.v26.i38.5759
Peer-review started: August 14, 2020
First decision: August 22, 2020
Revised: September 3, 2020
Accepted: September 17, 2020
Article in press: September 17, 2020
Published online: October 14, 2020
Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis, cancer, and liver failure. Liver cancer is the third leading cause of cancer-associated mortality, of which hepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management. Chronic infection with hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) are the greatest etiological risk factors for HCC. Due to the significant role of chronic viral infection in HCC development, it is important to investigate direct (viral associated) and indirect (immune-associated) mechanisms involved in the pathogenesis of HCC. Common mechanisms used by HBV, HCV, and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response, immune and viral protein-mediated oxidative stress, and deregulation of cellular signaling pathways by viral proteins. DNA integration to promote genome instability is a feature of HBV infection, and metabolic reprogramming leading to steatosis is driven by HCV infection. The current review aims to provide a brief overview of HBV, HCV and HDV molecular biology, and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC, and current as well as emerging treatments for HCC.
Core Tip: Hepatocellular carcinoma (HCC) is a dreaded complication of viral infection with hepatitis B virus and/or hepatitis delta virus and hepatitis C virus. Many of the direct and indirect molecular mechanisms used by these viruses to co-opt the liver microenvironment for persistence also disrupt cell cycle pathways. Indirectly, the immune system has a major role in the contribution of HCC in the context of viral hepatitis, but direct viral mechanisms also create a pro-tumorigenic environment.