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J Hepatol. 2008 Jun;48(6):923-31. doi: 10.1016/j.jhep.2008.02.019. Epub 2008 Apr 1.

Low risk of adefovir resistance in lamivudine-resistant chronic hepatitis B patients treated with adefovir plus lamivudine combination therapy: two-year follow-up.

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  • 1Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.



We studied the long-term efficacy (median follow-up of 28 months) of adefovir (ADV) in combination with lamivudine (LAM) in 132 LAM-resistant Japanese patients with chronic genotype C-dominant hepatitis B virus (HBV) infection.


The viral response (undetectable HBV-DNA by PCR assay) and the predictor of viral response were evaluated. The emergence of ADV-resistant mutants was investigated during the combination therapy.


The cumulative probability of viral response was 69% at 12 months, and 81% at 24 months. Multivariate analysis identified baseline HBe antigen status (P=0.0001), aspartate aminotransferase level (AST) (P=0.001) and HBV-DNA level (P=0.002) as determinants of viral response to treatment. At the beginning of ADV therapy, substitutions at rtA181 (rtA181T and rtA181S) were identified in 3 patients (2.3%). In the remaining 129 patients, the rtM204 mutants were identified at baseline, and two (1.6%) of the 129 patients developed new ADV-resistant mutants; one was rtA181S and another was rtA181T plus rtN236T mutation.


Adefovir and lamivudine combination therapy effectively suppressed viral replication and maintained the efficacy well in LAM-resistant patients with chronic HBV infection. Genotypic analysis indicated that the emergence of ADV-resistant mutants is rare, at least over a period of 2 years, in patients with combination therapy.

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