A case of chronic hepatitis B with primary adefovir resistance

Implementation of antiviral therapy leads to the emergence of mutant strains during the treatment in chronic hepatitis B. Hepatitis 6 virus (HBV) with primary antiviral resistance may be rarely encountered. In this report, a chronic hepatitis B case who had never received adefovir dipivoxil but had primary adefovir resistance, was presented. HBeAg positive 25-year-old male patient was treated with interferon (IFN)alpha (thrice a week 10 MU) and lamivudine (100 mg/daily) combination for one year. At the end of this treatment although HBV-DNA was under the detectable limit and ALT levels returned to normal, anti-HBe antibodies did not develop. During the course of lamivudin treatment on the third year virus was found to be resistant to lamivudin [FLM+YMDD+YIDD+YVDD (Inno-LiPA HBV DR, Innogenetics Ghent, Belgium)] and adefovir was added to the lamivudin therapy. At the end of eight months of combination therapy, ALT levels did not return to normal and HBV-DNA was still in detectable levels. On the 11(th) month resistance to adefovir was analysed and rtA181T mutation was found by DNA sequence analysis (Big Dye Terminator Cycle Sequencing kit, Applied Biosystems, USA). Since there had been no response to adefovir from the initiation of the therapy, primary adefovir resistance was suspected. Primary adefovir resistance was confirmed by the detection of the same mutation in pre-adefovir treatment serum sample of the patient. Lamivudin was re-added to the therapy, however, HBV-DNA still remained positive on the third month of this combination therapy. The patient got out of routine follow-up after this period.