Effect of nucleoside analogue therapy on duck hepatitis B viral replication in hepatocytes and bile duct epithelial cells in vivo

Background: Recent studies have implicated bile duct epithelial cells (BDEC ) as a reservoir of hepatitis B virus (HBV) infection that may be particula rly important in the development of post-liver transplant recurrence of hep atitis B. The aim of this study was to compare the effects of antiviral the rapy on duck HBV (DHBV) expression in hepatocytes and BDEC and to determine if this was affected by biliary hyperplasia. Methods: Ducklings congenitally infected with DHBV received penciclovir (10 mg/kg per day) treatment from 9 days of age. In order to mimic the biliary hyperplasia that often accompanies severe post-liver transplant HBV recurr ence, half the animals underwent bile duct ligation. Duck HBV-DNA in serum was measured at day 1, and serum and liver DHBV-DNA were determined when th e animals were killed on day 17. Intrahepatic expression of viral preS1 ant igen and DHBV-DNA was measured by immunohistochemistry and in situ hybridiz ation, respectively. Results: Viraemia became undetectable in the penciclovir-treated animals at day 17, following 8 days of therapy. Examination of liver tissue revealed that all hepatocytes and the majority of BDEC contained DHBV preS1 antigen and DHBV-DNA. Penciclovir greatly reduced the intrahepatic viral burden, bu t there was no antiviral effect on viral markers within BDEC. Despite the i ncreased number of BDEC after bile duct ligation, the same proportion of BD EC was seen to be infected, and this was unaffected by antiviral therapy. Conclusions: In the duck model with and without biliary hyperplasia, pencic lovir controls DHBV replication and reduces viral burden in hepatocytes, bu t not in BDEC. The BDEC appear to be an important reservoir of virus that i s relatively unaffected by antiviral treatment, and may play an important r ole in disease persistence and relapse following cessation of therapy. (C) 2000 Blackwell Science Asia Pty Ltd.