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Basic Characteristics of Mutations
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Mutation Site
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A181V |
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Mutation Site Sentence
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The rtA181V/T mutations were predominantly identified during the ADV treatment in the LMV-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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C |
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Viral Reference
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GQ872210
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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
|
Lamivudine(LAM);Abacavir(ADV) |
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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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23197889
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Title
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Clonal evolution of hepatitis B virus polymerase gene mutations during lamivudine-adefovir combination treatment
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Author
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Ko SY,Kim BK,Kwon SY,Kim KH,Kim JH,Choe WH,Lee CH
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Journal
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World journal of gastroenterology
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Journal Info
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2012 Nov 28;18(44):6437-46; discussion p
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Abstract
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AIM: To identify hepatitis B virus polymerase gene mutations during antiviral therapy using lamivudine-adefovir sequential monotherapy followed by lamivudine-adefovir combination therapy. METHODS: The patient cohort included four adult chronic hepatitis B patients who had undergone sequential monotherapy, first with lamivudine (LMV) and then, after developing viral breakthrough, with adefovir (ADV) therapy. All of the patients had non-response or viral breakthrough after LMV-ADV sequential monotherapy, which resulted in the switching of their antiviral regimen to LMV-ADV combination therapy. Eleven serum samples from the four patients who showed non-response to rescue LMV-ADV combination therapy were collected sequentially at a time before the antiviral treatment and then during the LMV monotherapy, ADV monotherapy, and LMV-ADV combination therapy. For the genotypic analysis, the whole 1310-bp polymerase gene region was amplified, cloned and sequenced. RESULTS: All patients had been previously treated with 100 mg of LMV once daily for a 15- to 26-mo period. The emergence of resistance mutations to LMV, such as rtM204V/I and/or rtL180M, were found in all patients. Their antiviral regimens were switched to ADV monotherapy as the second line treatment. All patients had viral breakthrough or non-response after the LMV-ADV sequential monotherapy. ADV-resistant mutations were detected after 13 to 19 mo of LMV-ADV sequential monotherapy. The rtA181V/T mutations were predominantly identified during the ADV treatment in the LMV-resistant patients. Twenty-seven of 38 clones were combined with an amino acid change at rt181; three clones had mutations in rt236 and one clone had a combined mutation. The rtA181V/T mutations were not suppressed by the LMV-ADV combination therapy. Thirty-nine of 64 clones showed an rtA181V/T mutation and six clones showed combined mutations in rt181 and rt236. Mutations in rt204 re-emerged during the combination treatment. The rt181 and rt204 mutations did not co-exist in one clone. CONCLUSION: Add-on lamivudine therapy with adefovir for adefovir resistance may not suppress the pre-existing adefovir-resistant mutation that develops during lamivudine-adefovir sequential monotherapy.
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Sequence Data
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-
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