Viral and host factors and risk of hepatocellular carcinoma

PL05-02

Viral hepatitis is a significant problem worldwide. There are about 350 million chronic carriers of hepatitis B virus (HBV) and 170 million chronic carriers of hepatitis C virus (HCV). The exact number of people infected with both HBV and HCV is unknown, although dual HBV and HCV infection is not uncommon in endemic areas of hepatitis B. Chronic HBV and/or HCV infection can progress to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Globally, approximately 78% of HCC cases are attributable to either HBV (53%) or HCV (25%). The relative importance of HBV and HCV in the etiology of HCC varies by region. Perhaps the most striking characteristic of HCC is its marked variation among geographical regions. About 80% of the HCC cases occur in developing countries, but the incidence of HCC is increasing in many developed countries. While the effect of monoinfection with HBV or HCV on the risk of HCC is well described, the relation of dual HBV and HCV infection to HCC is not fully characterized because of the paucity of adequate long-term cohort study. Chronic HBV or HCV infection increases the risk of the development of HCC 20 to 40-fold. However, only a small fraction of HBV or HCV carriers develop HCC in their lifetime. This suggests that chronic hepatitis virus infection is not a sufficient cause of HCC. It becomes evident that multiple factors, including host-related, virus-related, and external factors, have roles in the etiology of HCC among HBV/HCV carriers. This presentation will focus on current findings from prospective follow-up studies, including (1) investigation of the risks of incident HCC and liver-related death for monoinfection by HBV or HCV in comparison to dual infection of HBV and HCV in hospital- and population-based studies; (2) results of the analyses on the familial risk of HCC after accounting for the context of HBV exposure and adjusting for other potential confounders; as well as (3) recent investigations of serological viral markers derived from molecularly based assays, such as viral load, genotype, and intragenotypic variants, and the risk of HCC. These data highlight the importance of population-based study in evaluation of HCC natural history, and suggest that understanding the complex interplay between different viral factors and between host and viral factors is important for distinguishing individuals who are infected with hepatitis virus at the highest risk of progression to HCC.