[Epidemiology, natural history and pathogenesis of hepatocellular carcinoma].

Hepatocellular carcinoma is one of the most prevalent tumors worldwide and its incidence is increasing due to hepatitis C virus infection. Other etiologic factors are hepatitis B virus infection, alcoholic liver disease and hemochromatosis. This tumor mainly develops in cirrhotic livers that are true precancerous states. Although mechanisms of hepatocarcinogenesis remain badly known, some signaling pathways are frequently deregulated: inactivation of the p53 tumor suppressor factor in 25% of HCC, activation of the Wnt signaling and the telomerase immortalization enzyme in most of tumors. Hepatitis viruses play a direct oncogenic role by interaction between viral proteins and cellular ones, which control cell homeostasis, or by integration of hepatitis B virus genome into the host genome. Furthermore, hepatitis viruses play an indirect oncogenic role by chronic inflammation and hepatocyte regeneration related to viral hepatopathy. In a near future, a better understanding of virus-specific oncogenic mechanisms should allow us to set up innovative preventive and curative therapeutic strategies.