Decrease of wild-type and precore mutant duck hepatitis B virus replication during lamivudine treatment in white Pekin ducks infected with the viruses

Background/Aims: Lamivudine, an antiviral agent, has been used in the treatment of chronic hepatitis B, but little is known about its effect on intrahepatic replication of hepatitis B virus. We investigated the effect of lamivudine on the replication of wild-type and precore mutant duck hepatitis B virus (DHBV) in the liver and serum of DHBV carrier ducks. Methods: Chronic carrier ducks with either wild-type or precore mutant DHBV were treated for 2 weeks with either low-dose (20 mg/kg, p.o., b.i.d.) or high-dose lamivudine (100 mg/kg, p.o., b.i.d.) or were untreated. Serum levels of DHBV DNA were examined serially by slot-blot hybridization. A second group of chronic carrier ducks was treated for 12 weeks with lamivudine (100 mg/kg, p.o., b.i.d.) or was untreated. The amount of DHBV DNA in serum and its various replicative intermediates in the liver were serially examined by slot-, Southern, and Northern blot methods. Results: In the 2-week treatment study, concentration of DHBV DNA in serum treated with low- and high-dose lamivudine was reduced to 10.8% and 1.1% of the control level in wild-type DHBV carriers, and to 2.3% and 0.48% in precore mutant DHBV carriers, respectively. In the 12-week treatment study, concentration of DHBV DNA in serum at the end of treatment was reduced to <0.65% and <5.36% in wild-type and precore mutant DHBV carriers, respectively. Southern and Northern blot analyses revealed that the various replicative forms of DHBV DNA in the liver were decreased in all treated ducks, but, covalently closed circular DNA and RNA intermediates tended to remain unchanged. Conclusions: Our results showed that lamivudine could reduce both wild-type and precore mutant DHBV levels in the liver through inhibition of the reverse transcription step, but complete elimination of the viruses from liver is difficult even by relatively long-term lamivudine monotherapy, suggesting a need for some additional therapy to obtain complete clearance.