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Tumour, cirrhotic, and metastatic tissues from four patients with primary hepatocellular carcinoma have been investigated for the presence of hepatitis B viral DNA by nucleic acid hybridization. Tumours from two of three patients with a current HBV infection contained 1--2 genomes per cell of unintegrated viral DNA, while tumours from the third HBs antigen-positive patient contained less than one genome equivalent per ten cells. A tumour from one patient with anti-HBs contained no detectable HBV DNA. A variety of models involving HBV as an etiologic agent may be advanced to explain the statistical correlation of HBV infection with primary hepatocellular carcinoma (PHC). The data presented here argue against the model that HBV DNA integrated into every cell is required to maintain the oncogenic transformation of hepatocytes, but they do not rule out other models.
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