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Basic Characteristics of Mutations
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Mutation Site
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N424D |
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Mutation Site Sentence
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In patients with a breakthrough, 378V➡️I and 424-N➡️D mutations emerged in the N terminal part of the polymerase domain during follow-up. |
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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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P |
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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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- |
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Treatment
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Famciclovir(FCV) |
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Location
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- |
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Literature Information
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PMID
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10365797
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Title
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Absence of mutations in the YMDD motif/B region of the hepatitis B virus polymerase in famciclovir therapy failure
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Author
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Gunther S,von Breunig F,Santantonio T,Jung MC,Gaeta GB,Fischer L,Sterneck M,Will H
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Journal
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Journal of hepatology
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Journal Info
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1999 May;30(5):749-54
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Abstract
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BACKGROUND/AIMS: Nucleoside analogues such as lamivudine and famciclovir are potent drugs for treatment of chronic hepatitis B virus infection. Breakthrough infections during lamivudine therapy are associated with mutations in the YMDD motif and putative B region of the HBV polymerase. This study investigated whether failure of famciclovir therapy is also associated with presence or emergence of particular mutations in the HBV polymerase. METHODS: We analyzed longitudinally the sequence of the priming and polymerase domain in seven patients with primary non-response to therapy and two patients with a breakthrough during therapy. Two patients who responded to therapy served as a control. RESULTS: The YMDD motif and the B region were conserved in all isolates. V-->I changes at position 555 just downstream of the YMDD motif were observed before and during therapy in a virus subpopulation of two patients with a primary non-response. In patients with a breakthrough, 378-V-->I and 424-N-->D mutations emerged in the N terminal part of the polymerase domain during follow-up. Lamivudine rescue therapy initiated in four patients, including a patient infected with YMDD(555-V-->I) variants, efficiently reduced viremia. CONCLUSIONS: These data indicate that failure of famciclovir therapy can occur independently of mutations in the YMDD motif or B region of the HBV polymerase and provide a rationale for rescue therapy with lamivudine.
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Sequence Data
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-
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