Low risk of adefovir resistance in lamivudine-resistant chronic hepatitis B patients treated with ad

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J Hepatol. 2008 Apr 1 [Epub ahead of print]

Low risk of adefovir resistance in lamivudine-resistant chronic hepatitis B

patients treated with adefovir plus lamivudine combination therapy: Two-year

follow-up.

Yatsuji H, Suzuki F, Sezaki H, Akuta N, Suzuki Y, Kawamura Y, Hosaka T,

Kobayashi M, Saitoh S, Arase Y, Ikeda K, Watahiki S, Iwasaki S, Kobayashi M,

Kumada H.

Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo

105-8470, Japan.

BACKGROUND/AIMS: 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. METHODS: 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. RESULTS:

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.

CONCLUSIONS: 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.

PMID: 18433925 [PubMed - as supplied by publisher]

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