The pattern of replicative intermediates seen in the liver of HBe antigen and antibody positive patients was determined. During the phase of HBe antigenaemia the 3.2 Kb species of HBV-DNA (complete HBV genome) is present in the liver but not in the serum. When HBe antigen to antibody seroconversion occurs, either spontaneously or during antiviral therapy, the 3.2 Kb and lower molecular weight intermediates disappear from the liver and the 3.2 Kb band appears transiently in the serum. Integrated HBV-DNA was found in one of 15 patients during the period of HBe antigenaemia and in three of seven patients in the HBe antibody positive phase of the chronic infection before detection of primary liver cell carcinoma. Integrated sequences were found in tumour tissue of two patients with primary liver cell carcinoma who were anti-HBc positive but were absent from the tissues of two patients developing primary liver cell carcinoma at a late stage of autoimmune liver disease. These studies suggest that integration of the HBV genome occurs rarely or in only a small proportion of hepatocytes during the early (HBe antigen positive) phase of infection in Caucasians. They also show that not all primary liver cell carcinomas necessarily contain HBV-DNA.
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