Hepatitis B virus RNA transcripts and DNA in chronic liver disease

To study the relation between gene expression of hepatitis B virus (HBV) and liver disease, we studied HBV RNA transcripts and DNA in liver-biopsy specimens from 30 patients with chronic liver disease (17 seropositive for hepatitis B surface antigen and 13 seronegative). HBV-specific RNA was found in all the seropositive patients and in none of the seronegative patients. Two major RNAs, sizes 29S (long) and 21S (short), were found in nine seropositive patients, of whom seven had free HBV DNA and eight were seropositive for hepatitis B e antigen. Six of the nine patients had hepatitis B core antigen in hepatocytes and active liver disease. In contrast, inactive liver disease was noted in the remaining eight seropositive patients, who had only one (21S) RNA. None of these patients had free HBV DNA (five of eight had integrated DNA) or hepatitis B core antigen in hepatocytes. Hybridization analysis suggested that 29S and 21S RNAs are messenger RNAs of hepatitis B core antigen and hepatitis B surface antigen, respectively. These data indicate that the free DNA and its products are causally related to the activity of liver disease and that once HBV DNA has been integrated, the disease will become quiescent. None of the determinants were identified in patients seronegative for hepatitis B surface antigen.