CHARACTERIZATION OF THE ANTIVIRAL EFFECTS OF 2' CARBODEOXYGUANOSINE IN DUCKS CHRONICALLY INFECTED WITH DUCK HEPATITIS-B VIRUS

This study was carried out to evaluate benefits and limitations of lon g-term therapy of hepatitis B virus infections with a nucleoside analo g inhibitor of virus replication. The model we used was the domestic d uck chronically infected with duck hepatitis B virus by in ovo infecti on. 2' Carbodeoxyguanosine was used as an inhibitor of viral DNA synth esis. In all animals examined there was a reduction in virus productio n during therapy. A dose of 2' carbodeoxyguanosine of 10 mu g/kg every other day reduced the number of infected hepatocytes from greater tha n 95% to 25% to 50% in less than 3 mo, whereas a 10-fold higher dose p roduced a decline to less than 10%. Histological evaluation revealed m ild to moderate liver injury in ducks receiving the higher dose of 2' carbodeoxyguanosine, suggesting that disappearance of infected hepatoc ytes may have been accelerated by a toxic effect of the drug. Drug tre atment did not completely eliminate duck hepatitis B virus from any du ck, and replication was restored in all hepatocytes within a few weeks to several months after antiviral therapy was terminated. Our results suggest that elimination of a chronic infection with a single inhibit or of replication may be difficult in a host that lacks an antiviral i mmune response capable of eliminating at least a portion of the infect ed hepatocytes and of ultimately producing antibodies capable of neutr alizing residual virus.