[Hepatocellular carcinoma, hepatitis B virus and the immune system].

Epidemiologically, two main geographical areas for hepatocellular carcinoma (HCC) can be distinguished: China, other parts of Asia and parts of Africa are high incidence zones for HCC. The HBsAg-associated form accounts for more than 90% of all cases. HBV-infections are frequent and most often occur early in life. Also, the prevalence of HBsAg carriers is high. HCC most often appears in midlife and in patients with formerly quiescent chronic hepatitis and cirrhosis. The USA, Western and Northern Europe represent low incidence zones for HCC, with the HBsAg-associated form accounting for less than 40% of all cases. HBV infections occur less frequently and most often after adolescence. The HBsAg carrier rate is low. HCC most often develops in elderly men with formerly active chronic hepatitis and cirrhosis. For the development of HBsAg-associated HCC the integration of viral DNA (HBV-DNA) into the host genome seems crucial; it may occur after a longterm productive HBV infection which is then associated with a semi- or non-productive infection. Initially the HBV-DNA is integrated at random and later becomes monoclonal. HBsAg negative HCC may be due to oncogenic stimuli resulting from recurrent bouts of liver destruction and regeneration induced by alcohol, other hepatotoxic substances or by the virus(es) responsible for chronic non-A/non-B hepatitis. Defective immune elimination of HBV-infected cells also appears crucial for the development of HCC, in three stages: initially not all HBV-infected cells are destroyed and chronic infection results. Then cells with latent HBV infection are insufficiently eliminated and finally HCC-cells escape from immune elimination altogether. Hepatitis B vaccination is the most promising measure for prevention of HBsAg-associated HCC. Other strategies such as immune modulation and/or virostatic principles are considered.