The role of HBV in HBsAg-negative patients with liver cancer has been debated. We and others have previously detected HBV DNA sequences in the liver and serum of blood donors and patients with chronic hepatitis and hepatocellular carcinoma, although HBsAg was not identified in serum by conventional assays. However, the frequency of these findings remains controversial, since other investigators have been unable to demonstrate the presence of viral DNA and RNA in HBsAg-negative patients. These discrepancies may be linked to epidemiologic differences in the prevalence of exposure to HBV or possibly technical problems with Southern blotting (including both specificity and sensitivity). Comparing HBsAg-positive with HBsAg-negative tumors clearly shows that in the latter, the number of viral genomes per cell is much lower.


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