Bile duct epithelial cells (BDEC) as a reservoir of HBV

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J Gastroenterol Hepatol 2000 Mar;15(3):304-10

Effect of nucleoside analogue therapy on duck hepatitis B viral replication

in hepatocytes and bile duct epithelial cells in vivo.

Nicoll A, Locarnini S, Chou ST, Smallwood R, Angus P

n Infectious Diseases Reference Laboratory, North Melbourne,

Australia.

BACKGROUND:

Recent studies have implicated bile duct epithelial cells (BDEC) as a

reservoir of hepatitis B virus (HBV) infection that may be particularly

important in the development of post-liver transplant recurrence of

hepatitis B.

The aim of this study was to compare the effects of antiviral therapy 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 recurrence, 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 the animals were killed on

day 17. Intrahepatic expression of viral preS1 antigen and DHBV-DNA was

measured by immunohistochemistry and in situ hybridization, 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, but

there was no antiviral effect on viral markers within BDEC. Despite the

increased number of BDEC after bile duct ligation, the same proportion of

BDEC was seen to be infected, and this was unaffected by antiviral therapy.

CONCLUSIONS:

In the duck model with and without biliary hyperplasia, penciclovir controls

DHBV replication and reduces viral burden in hepatocytes, but not in BDEC.

The BDEC appear to be an important reservoir of virus that is relatively

unaffected by antiviral treatment, and may play an important role in disease

persistence and relapse following cessation of therapy.

PMID: 10764033, UI: 20225103