Characterization of the antiviral effects of 2' carbodeoxyguanosine in ducks chronically infected with duck hepatitis B virus

W S Mason, J Cullen, J Saputelli, T T Wu, C Liu, W T London, E Lustbader, P Schaffer, A P O'Connell, I Fourel
Hepatology: Official Journal of the American Association for the Study of Liver Diseases 1994, 19 (2): 398-411
This study was carried out to evaluate benefits and limitations of long-term therapy of hepatitis B virus infections with a nucleoside analog inhibitor of virus replication. The model we used was the domestic duck chronically infected with duck hepatitis B virus by in ovo infection. 2' Carbodeoxyguanosine was used as an inhibitor of viral DNA synthesis. In all animals examined there was a reduction in virus production during therapy. A dose of 2' carbodeoxyguanosine of 10 micrograms/kg every other day reduced the number of infected hepatocytes from greater than 95% to 25% to 50% in less than 3 mo, whereas a 10-fold higher dose produced a decline to less than 10%. Histological evaluation revealed mild to moderate liver injury in ducks receiving the higher dose of 2' carbodeoxyguanosine, suggesting that disappearance of infected hepatocytes may have been accelerated by a toxic effect of the drug. Drug treatment did not completely eliminate duck hepatitis B virus from any duck, 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 inhibitor of replication may be difficult in a host that lacks an antiviral immune response capable of eliminating at least a portion of the infected hepatocytes and of ultimately producing antibodies capable of neutralizing residual virus.

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