HBsAg-positive chronic liver disease: inhibition of DNA polymerase activity by vidarabine.
Four patients who had chronic liver disease and were positive for hepatitis B surface antigen (HBsAg) were treated with vidarabine, a synthetic purine nucleoside that inhibits DNA polymerase activity in vitro and in vivo. Before treatment all had raised serum DNA polymerase concentrations. Three also had hepatitis B e (HBe) and were shown by electron microscopy to have hepatitis B virus (Dane) particles in their serum. In all patients 10 days' treatment with vidarabine resulted in an immediate loss of DNA polymerase activity. In three patients the activity returned when treatment was stopped. In those three patients Dane particles and HBe antigen persisted during and after treatment; in the fourth patient, who remained negative for DNA polymerase, HBsAg titres fell. Although vidarabine inhibited virus replication, virus particles did not disappear from the blood in these patients, presumably because the particles were cleared only slowly. Similar results with interferon suggest that the virus disappears, and HBsAg titres fall, some weeks after the fall in DNA polymerase activity. Continued treatment may therefore have a sustained effect on viral replication. Whether vidarabine can permanently clear HBsAg and so arrest chronic liver disease remains to be seen, but at the very least it could reduce the spread of infection.
D000328:Adult; D004259:DNA-Directed DNA Polymerase / Q000097:blood; D006509:Hepatitis B / Q000188:drug therapy* / Q000201:enzymology* / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019384:Nucleic Acid Synthesis Inhibitors; D014740:Vidarabine / Q000627:therapeutic use*
D006514:Hepatitis B Surface Antigens; D019384:Nucleic Acid Synthesis Inhibitors; D004259:DNA-Directed DNA Polymerase; D014740:Vidarabine