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Basic Characteristics of Mutations
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Mutation Site
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L180M |
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Mutation Site Sentence
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The L180M/M204I (double mutation) of the polymerase region occurred in only one patient at the time of BTH (Fig. 3). |
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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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- |
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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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15338371
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Title
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Prognostic indicators of breakthrough hepatitis during lamivudine monotherapy for chronic hepatitis B virus infection
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Author
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Tanaka Y,Yeo AE,Orito E,Ito K,Hirashima N,Ide T,Sata M,Mizokami M
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Journal
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Journal of gastroenterology
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Journal Info
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2004 Aug;39(8):769-75
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Abstract
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BACKGROUND: Breakthrough hepatitis (BTH), defined as a flare of transaminases alanine aminotransferase [ALT]) can occur during lamivudine monotherapy for hepatitis B virus (HBV) infection. There have been many reports of lamivudine-resistant mutations within the C domain of the viral reverse transcriptase; however, the appearance of these mutants is not necessarily correlated with BTH during lamivudine therapy. METHODS AND RESULTS: Entire serial HBV genomic sequences before and during lamivudine therapy for 4 patients with BTH and 1 patient without BTH were analyzed and showed changes in the pre-S region. These changes may be associated with ALT flares. Further investigation in a cohort of 36 patients with a median treatment period of 25 months showed that 21 patients had a rise in HBV-DNA titer, of whom 18 had BTH. Univariate statistical analyses showed that possible prognostic indicators for the occurrence of BTH were pre-S deletions ( P = 0.03) and L180M/M204L mutations ( P = 0.04). By multivariate Cox regression analyses, significant variables were pre-S deletions (hazard ratio, 0.17; 95% confidence internal (CI), 0.044-0.66) and precore mutations (hazard ratio, 5.70; 95% CI, 1.74-18.71) prior to the commencement of lamivudine monotherapy. Interestingly, BTH occurred after the selection of the wild-type species in the pre-S region during lamivudine monotherapy. CONCLUSIONS: These results suggest that patients with HBV pre-S deletion mutants should be monitored carefully during lamivudine therapy.
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Sequence Data
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-
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