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 treat ment of chronic hepatitis B, but little is known about its effect on intrah epatic replication of hepatitis B virus. We investigated the effect of lami vudine 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 lev els of DHBV DNA were examined serially by slot-blot hybridization. A second group of chronic carrier ducks was treated for 12 weeks with lamivudine (1 00 mg/kg, p.o., b.i.d.) or was untreated. The amount of DHBV DNA in serum a nd its various replicative intermediates in the liver were serially examine d 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 pre core mutant DHBV carriers, respectively. In the 12-week treatment study, co ncentration 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, co valently closed circular DNA and RNA intermediates tended to remain unchang ed. Conclusions: Our results showed that lamivudine could reduce both wild-type and precore mutant DHBV levels in the liver through inhibition of the reve rse transcription step, but complete elimination of the viruses from liver is difficult even by relatively long-term lamivudine monotherapy, suggestin g a need for some additional therapy to obtain complete clearance.