Molecular hybridisation using cloned hepatitis B virus DNA (HBV DNA) was applied to liver and serum samples from 46 children (39 with liver diseases and seven controls) for detection of HBV DNA sequences, free and integrated into the liver cell genome. HBV DNA integration was observed in 10 children. The young age of some of these cases indicates that such integration can occur early in liver disease and is not related to the duration of viral infection. Thirteen children exhibited serological evidence of active viral multiplication. All but one had free HBV DNA in liver tissue and integrated HBV DNA sequences were found in four cases. Integrated HBV DNA sequences alone were also detected in three children with neither HBV-antigens nor HBV DNA in serum. One had inactive cirrhosis, and the two others, chronic active hepatitis. Consequently DNA hybridisation may be useful for diagnosis, in the absence of serological signs of HBV infection; its specificity was enhanced in the present investigation by negative results in six children with autoimmune chronic active hepatitis. Taken together, the above results imply that HBV-DNA integration can occur in both active and inactive liver disease. Integrated HBV DNA was also observed in the liver of three children with fatal hepatic failure who presented with antibodies to HBsAg and/or to hepatitis B core antigen in the serum. This finding raises the question of the relationship between the host immune factors and the state of HBV DNA.
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