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Basic Characteristics of Mutations
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Mutation Site
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M204V |
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Mutation Site Sentence
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The methodology was validated by a clonal sequencing assay for successful detection of rtM204I/V mutations in LAM‐resistant patients |
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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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- |
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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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Lamivudine(LAM);Clevudine(L-FMAU);Entecavir(ETV);Tenofovir(TDF) |
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Location
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- |
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Literature Information
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PMID
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16729316
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Title
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Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy
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Author
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Lee YS,Suh DJ,Lim YS,Jung SW,Kim KM,Lee HC,Chung YH,Lee YS,Yoo W,Kim SO
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Journal
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Hepatology (Baltimore, Md.)
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Journal Info
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2006 Jun;43(6):1385-91
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Abstract
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Although adefovir dipivoxil (ADV) has a unique profile of delayed and infrequent resistance in treatment-naive chronic hepatitis B patients, the association of ADV resistance with previous lamivudine (LAM) resistance is not well understood. We compared the emergence of the ADV-resistant mutations rtA181V/T and rtN236T between LAM-resistant patients and treatment-naive patients at 48 weeks of ADV monotherapy. Fifty-seven LAM-resistant patients and 38 treatment-naive patients were treated with 10 mg/d ADV for more than 48 weeks. Both baseline and 48-week blood samples were analyzed for ADV-resistant mutations via restriction fragment mass polymorphism analysis. Antiviral responses were evaluated according to changes in serum HBV DNA (measured via real-time polymerase chain reaction) and alanine aminotransferase (ALT) levels and loss of hepatitis B e antigen (HBeAg). After 48 weeks, 10 (18%) of the 57 LAM-resistant patients were found to have developed ADV-resistant mutations, whereas none of the 38 treatment-naive patients developed such mutations (P < .01). Among LAM-resistant patients, the reduction in serum HBV DNA levels was significantly lower in patients with ADV-resistant mutations than in those without such mutations (-1.04 vs. -2.63 log10 copies/mL) (P = .01). However, the rates of serum ALT normalization (60% vs. 55%) and HBeAg loss (14% vs. 21%) were not significantly different between the 2 groups (P > .05). In conclusion, the emergence of the rtA181V/T and rtN236T mutations was more common in LAM-resistant patients than in treatment-naive patients after 48 weeks of ADV therapy and was associated with reduced antiviral efficacy to drug treatment.
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Sequence Data
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-
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