Relationship between serum and histochemical markers for hepatitis B virus and rate of viral integration in hepatocellular carcinomas in Japan.

The relationship between serological and histochemical markers of hepatitis B virus (HBV) and viral integration in hepatocellular carcinomas (HCCs) in Japan was investigated. Special attention was paid to the exclusion of false-positive results due to bacterial contamination of autopsy materials. Of 85 patients with HCC, 23 were positive for serum HBsAg, 18 were positive for serum HBV antibodies and the remaining 44 were negative for serum HBV markers. Among the 23 HCCs from HBsAg carriers, 19 (82.6%) had integrated HBV DNA in the tumor DNA. In contrast, of the 18 HCCs from HBV antibody-positive patients, only one was positive for HBV DNA integration; this particular HCC was from a long-term HBsAg carrier who became a non-carrier by seroconversion at a later age. Of 44 HCCs from patients negative for serum HBV markers, 3 had integrated HBV DNA. Of these 3 cases, 2 were, however, histochemically positive for HBsAg in non-cancerous portions of the liver. Thus, our present results show a high integration rate of HBV DNA in HCCs of carrier patients and an extremely low rate of viral integration in HCCs of non-carrier patients. The latter finding contrasts strongly with previous results gained from analysing materials from patients in Europe and Africa. No histological differences were apparent between HCCs with or without viral integration.