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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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All patients had genotype C HBV infections and harbored rtM204V/I mutations. |
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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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Lamivudine(LAM) |
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Location
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Korea |
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Literature Information
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PMID
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21777282
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Title
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rtL180M mutation of hepatitis B virus is closely associated with frequent virological resistance to adefovir dipivoxil therapy
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Author
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Lee YS,Chung YH,Kim JA,Jin YJ,Park WH,Kim SE,Lee D,Shim JH,Kim KM,Lim YS,Lee HC,Lee YS,Suh DJ
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Journal
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Journal of gastroenterology and hepatology
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Journal Info
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2012 Feb;27(2):300-5
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Abstract
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BACKGROUND AND AIM: We intended to investigate the effects of pre-existing mutations at reverse transcriptase region of hepatitis B virus (HBV) on the occurrence of virological breakthrough (VB) to adefovir dipivoxil (ADV) in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB). METHODS: Ninety-seven patients with LAM-resistant CHB were treated with ADV at a dose of 10 mg daily, and were followed for a median period of 13 months. Just before the initiation of ADV therapy, the whole length of reverse transcriptase region of serum HBV-DNA was sequenced using direct sequencing. RESULTS: All patients had genotype C HBV and mutations in the YMDD motif, specifically, YIDD (65%), YVDD (28%), or both (7%). The rtL180M and rtL80V/I mutations were identified in 68% and 69%, respectively. The cumulative probability of VB was 19% and 27% at 1 and 2 years, respectively. There was no difference in the occurrence of VB with regard to types of YMDD mutation or rtL80V/I. However, interestingly, patients carrying rtL180M experienced VB during ADV monotherapy more frequently than those not carrying rtL180M (2-year cumulative probability of VB: 37% vs 3% at 2 years, P < 0.01). On multivariate Cox proportional hazards analysis, rtL180M (hazard ratio [HR]: 8.62, 95% confidence interval: 1.08-69.09, P = 0.042) and decrease in HBV-DNA for 1 year of treatment (HR: 0.69, 95% CI: 0.51-0.95, P = 0.024) are independently associated with VB. CONCLUSIONS: The rtL180M mutation of HBV, as well as a small decrease in HBV-DNA after 1 year of treatment might be closely associated with frequent occurrence of virological resistance to ADV in patients with LAM-resistant CHB.
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Sequence Data
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-
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