Hepatitis B viral DNA in infected human liver and in hepatocellular carcinoma

Blot-hybridization analysis of DNA forms from hepatitis B virus (HBV) in the liver of chronic carriers of hepatitis B surface antigen (HBsAg) has revealed the presence of both relaxed and closed circular viral DNA and of novel viral DNA-RNA hybrid molecules in patients with complete virions, with the hepatitis B e antigen (HBeAg), or with both, in serum. One carrier of HBsAg with no detectable virus or HBeAg in his serum had small amounts of free viral DNA in his liver sample, a finding suggesting the potential for production of complete virus; another such carrier had only HBV DNA integrated in cellular DNA and, thus, may have lost the ability to replicate virus. The liver sample of one of eight patients with antibodies to HBsAg in his serum, but no HBsAg, contained small amounts of free viral DNA. Analysis of tissue from hepatocellular carcinoma revealed evidence for integrated viral DNA sequences in multiple-cellular DNA sites, and stoichiometric analysis suggested that the tumors were monoclonal in origin. These results demonstrate the presence of a new form of HBV in infected human liver and reveal that serological profiles are not always a reliable guide in determining the presence of potentially infectious forms of HBV in the liver.