Initial Virological Response and Viral Mutation with Adefovir Dipivoxil Added to Ongoing Lamivudine Therapy in Lamivudine-Resistant Chronic Hepatitis B

Abstract

Although adefovir dipivoxil (ADV) has been used for antiviral treatment of lamivudine (LAM)-resistant chronic hepatitis B (CHB) patients, the long-term efficacy of this treatment is not well understood. Initial virological response (IVR) has been reported to be an important factor in relation to the development of ADV-resistance. We therefore examined the factors associated with IVR and ADV mutation in these patients. Forty-nine LAM-resistant CHB patients with ADV add-on LAM therapy, 47% of whom were hepatitis B e-antigen (HBeAg)-positive with median treatment duration of 23 months, were enrolled in this study. Patients were classified into IVR and non-IVR groups on the basis of viral suppression status. Mutational analysis of the HBV polymerase/reverse transcriptase (rt) domain was performed by PCR-direct sequencing. Serum HBV DNA was undetectable (<2.6 log10 copies/mL) in 67, 82, and 84% of patients at 24, 48, and 96 weeks, respectively, after ADV add-on LAM therapy. IVR was achieved in 82% of patients, and ALT normalized at week 24 in 90% of IVR and 78% of non-IVR patients. The lower pretreatment HBV DNA level and virus-containing mutations other than double mutation of rtL180M + rtM204V were significantly associated with IVR (P=0.002 and P=0.014, respectively). ADV-resistant mutations in the RT motif, reported previously, were not detected. IVR is useful for predicting the antiviral efficacy of ADV and LAM combination therapy in LAM-resistant CHB.