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Basic Characteristics of Mutations
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Mutation Site
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M204I |
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Mutation Site Sentence
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At baseline, substitutions at rtA181 were identified in 3 patients (2.3%), whose genotypes were rtA181T without substitution at rt204, rtA181S without substitution at rt204 and rtA181T plus rtM204I double mutation (Fig. 2). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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P
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Genotype/Subtype
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C |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Hepatitis B, Chronic
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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- |
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Location
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Japan |
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Literature Information
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PMID
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18433925
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Title
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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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Author
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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
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Journal
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Journal of hepatology
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Journal Info
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2008 Jun;48(6):923-31
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Abstract
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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.
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Sequence Data
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-
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