LONG-TERM GANCICLOVIR CHEMOTHERAPY FOR CONGENITAL DUCK HEPATITIS-B VIRUS-INFECTION IN-VIVO - EFFECT ON INTRAHEPATIC-VIRAL DNA, RNA, AND PROTEIN EXPRESSION

Long-term antiviral chemotherapy using the nucleoside analogue gancicl ovir was undertaken with the aim of eliminating hepadnaviral covalentl y closed circular (CCC) DNA from the livers of ducks that were congeni tally infected with the duck hepatitis B virus (DHBV). Twenty-four wee ks of ganciclovir therapy caused a substantial reduction in viremia, i ntrahepatic viral DNA replicative intermediates, and viral core protei ns. Unfortunately, ganciclovir therapy did not substantially affect CC C DNA or viral RNA levels, and the treatment resulted in an increase i n the intrahepatic expression of the viral envelope proteins, pre-S an d S. By the completion of therapy, the viral envelope proteins had ass embled into large aggregates within the cytoplasm of most hepatocytes. Viral replication in the bile duct epithelial cells and in the extrah epatic sites was likewise not affected by long-term ganciclovir therap y. In conclusion, 24 weeks of ganciclovir therapy decreased most viral replication markers within the liver, except for those of viral CCC D NA RNA, and envelope proteins. Long-term therapeutic strategies using nucleoside analogs such as ganciclovir should be used with caution in chronic hepatitis B virus (HBV) infection. The careful monitoring of s erum and hepatic markers of viral replication may therefore be importa nt to avoid possible toxic consequences, such as the selective accumul ation of viral proteins.