Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno Seodaemun-gu, Seoul, South Korea.
Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related mortality worldwide. Although hepatitis B still remains the most common risk factor worldwide, chronic hepatitis C virus (HCV) infection is the driving force for the increased incidence of HCC especially in Western countries and Japan. In hepatitis B virus (HBV)-endemic areas, after successful vaccination programs against HBV, chronic HCV infection is now emerging as an important cause of chronic liver diseases. Unlike patients with chronic hepatitis B, those with chronic hepatitis C (CHC) develop HCC in the presence of established cirrhosis in most cases. However, a significant minority of CHC develops HCC in the absence of cirrhosis. Although HCV is a RNA virus with little potential for integrating its genetic material into host genome, various HCV proteins, including core, envelope, and nonstructural proteins, have oncogenic properties by inducing oxidative stress, disturbing cellular regulatory pathways associated with proliferation and apoptosis, and suppressing host immune responses. Overall, a combination of virus-specific, host genetic, environmental, and immune-related factors are likely to determine progression to HCC. Strategies aimed at eliminating the virus may provide opportunities for effective prevention of the development of HCC. Pegylated interferon plus ribavirin therapy appears to be effective at reducing the risk of HCC in patients who achieve sustained virologic responses. In summary, with the emerging importance of CHC, mechanisms of HCV-associated hepatocellular carcinogenesis should be clarified to provide insight into advanced therapeutic and preventive approaches, which eventually decrease the incidence and mortality of HCC.