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Basic Characteristics of Mutations
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Mutation Site
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W172L |
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Mutation Site Sentence
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On the other hand, at the end of 3 years of ADV therapy, all rtA181T mutant strains changed to double nucleotide substitutions (TGG to TTA), which induced amino acid substitutions in both polymerase (rtA181T) and HBs antigen (HBs W172L) developed. |
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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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S |
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Standardized Encoding Gene
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S
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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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