State of hepatitis B virus DNA in hepatocytes of patients with hepatitis B surface antigen-positive and -negative liver diseases.

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Abstract
Using the Southern blot technique and cloned hepatitis B virus (HBV) DNA as a probe, the state of HBV DNA was studied in the liver of 13 patients with hepatocellular carcinoma, 17 patients with chronic hepatitis and 2 patients with acute hepatitis. The hybridization results were compared with the serological and immunohistological data. Integration of HBV DNA in cellular DNA of the liver from patients with hepatocellular carcinoma was demonstrated. In 2 patients from whom tumorous and nontumorous liver tissue samples were available, the integration patterns were different. In 1 patient with hepatitis B e antigen(HBeAg)-positive early hepatocellular carcinoma, free viral DNA was present in the liver. In some patients with HBeAg-negative chronic hepatitis without tumor, integration of HBV DNA in cellular DNA was also demonstrated. Thus HBV is not the only factor involved in the development of a tumor. In patients with HBeAg-positive chronic hepatitis, free viral DNA was detected in the liver. In the 2 acute hepatitis patients analyzed, the restriction endonuclease patterns strongly suggested HBV DNA integration. Thus, viral DNA integration seems to occur early in infection. Whatever the form of the disease, discrete bands were observed, suggesting the existence of limited and specific integration sites in host cellular DNA. The presence of integrated or free DNA sequences has implications for antiviral therapy. Detection of HBV DNA in the liver is another sensitive viral marker that could be useful for diagnostic purposes.