Using the Southern blot technique and cloned hepatitis B virus (HBV) DNA as a probe, we studied the state of HBV DNA 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 two patients from which tumorous and nontumorous liver tissue samples were available the integration patterns were different. In one 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. This suggests that 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 two acute hepatitis patients analyzed, the restriction endonuclease patterns strongly suggested HBV DNA integration. Therefore, viral DNA integration seems to occur early in infection. Whatever the form of the disease, discrete bands were observed, suggesting the existence oflimited and specific integration sites in host cellular DNA. The presence of integrated or free DNA sequences has implications for antiviral therapy. In addition, detection ofHBV DNA in the liver is another sensitive viral marker that could be useful for diagnostic purposes.Exposure to hepatitis B virus (HBV) can be followed by acute and chronic hepatitis (1). In addition, human HBV chronic carriers have a significantly increased risk of developing hepatocellular carcinoma (2). The Southern blot technique (3) using cloned HBV DNA as a probe (4) provides another approach to investigating the relationship between HBV and these pathological conditions. Presence and integration of HBV DNA sequences in the cellular DNA of hepatocellular carcinomas and of a hepatoma cell line (5-8) have been demonstrated. This observation is an additional argument for HBV as a factor in this human cancer. Thus, it is important to investigate the state of the viral DNA in chronic hepatitis and acute hepatitis. Additionally, the results of the hybridization technique should be compared to the serological and histological tests of HBV infection to evaluate its diagnostic usefulness. In this report, we present evidence for integration of HBV DNA in tumorous and nontumorous parts of the liver of patients with hepatocellular carcinoma and in the liver of patients with chronic and acute hepatitis B.

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