IDENTIFICATION OF HEPATITIS-B VIRUS-DNA IN THE LIVER BY IN-SITU HYBRIDIZATION USING A BIOTINYLATED PROBE - RELATION TO HBCAG EXPRESSION AND HISTOLOGY

The cellular localisation of hepatitis B virus (HBV)-DNA in liver tissue was studied by in situ hybridisation using biotinylated and radiolabelled probes on samples from HBsAg carriers with a spectrum of disease and related to the presence of HBV-DNA in serum and intrahepatic HBcAg expression. Sixteen of the 31 patients studied were seropositive for HBV-DNA; nine had chronic active hepatitis and seven had chronic persistent hepatitis. HBV-DNA was detected in the liver tissue in seven of these patients. In each, HBV-DNA was detected in both cytoplasm and nuclei. All seven also had nuclear and/or cytoplasmic HBcAg which in six was associated with chronic active hepatitis. HBcAg (without tissue HBV-DNA) was detected in the remaining nine patients with an exclusively nuclear pattern in two. Fifteen patients were seronegative for HBV-DNA. HBV-DNA was not detected in the tissue of any of these. Three of these were HBcAg positive but in each this was confined to occasional nuclei and each had inactive disease. The close association between the presence of detectable HBV-DNA in tissue, cytoplasmic HBV-DNA expression and chronic active hepatitis in one group and a failure to detect HBV-DNA in those with nuclear HBcAg and benign disease suggests that there may be two distinct patterns of HBV replication in chronic HBV carriers which may influence the development of liver damage.