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

The cellular localisation of hepatitis B virus (HBV)-DNA in liver tiss ue was studied by in situ hybridisation using biotinylated and radiola belled probes on samples from HBsAg carriers with a spectrum of diseas e and related to the presence of HBV-DNA in serum and intrahepatic HBc Ag expression. Sixteen of the 31 patients studied were seropositive fo r HBV-DNA; nine had chronic active hepatitis and seven had chronic per sistent hepatitis. HBV-DNA was detected in the liver tissue in seven o f these patients. In each, HBV-DNA was detected in both cytoplasm and nuclei. All seven also had nuclear and/or cytoplasmic HBcAg which in s ix was associated with chronic active hepatitis. HBcAg (without tissue HBV-DNA) was detected in the remaining nine patients with an exclusiv ely 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 t he presence of detectable HBV-DNA in tissue, cytoplasmic HBV-DNA expre ssion and chronic active hepatitis in one group and a failure to detec t 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.