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Basic Characteristics of Mutations
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Mutation Site
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V521L |
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Mutation Site Sentence
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One patient (NR21) selected a I68N and P120T corresponding to mutations N424K and T476N within the HBV-DNA polymerase, 2 patients (R03, PR11) selected a E164D corresponding to a V521L mutation within the HBV-DNA polymerase, 1 (R02) selected a Q120P mutation on FCV, and another 1 (R04) selected a W172Stop mutation of the HBsAg corresponding to a A529T mutation within the HBV-DNA polymerase. |
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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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ayw |
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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 Virus Infection
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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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- |
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Literature Information
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PMID
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10385663
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Title
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Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under HBIg immunoglobulin after liver transplantation
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Author
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Tillmann HL,Trautwein C,Bock T,Boker KH,Jackel E,Glowienka M,Oldhafer K,Bruns I,Gauthier J,Condreay LD,Raab HR,Manns MP
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Journal
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Hepatology (Baltimore, Md.)
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Journal Info
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1999 Jul;30(1):244-56
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Abstract
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Famciclovir (FCV) and lamivudine (LAM) reduce viral replication in patients with recurrent hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). Eighteen of 20 patients with insufficient response to FCV were treated with 100 mg LAM daily after OLT. These patients had shown nonresponse (n = 5), partial response (n = 7), or breakthrough (n = 6) during FCV therapy. Despite passive immunoprophylaxis with hepatitis B immunoglobulin after liver transplantation, HBV reinfection had occurred in 14 of 15 transplanted patients. HBV-DNA levels and the regions A to E of the HBV-DNA polymerase gene were analyzed before and after treatment failure to either therapy. Within 4 weeks on LAM, all but 1 patient showed a 95% average reduction of the HBV-DNA level. As with FCV, we did not observe any severe side-effects attributable to LAM. However, 7 patients developed a breakthrough within 12, 29 (n = 2), 32, 37, 54, and 145 weeks under treatment with LAM associated with the methionine-to-valine signature mutation (M552V) in the YMDD motif in all. With FCV, no unique, but a dominant, resistance pattern with the L528M mutation was identified for patients with breakthrough under FCV. In contrast, nonresponders or patients with partial response to FCV did not exhibit such mutations. Our results indicate that the L528M mutation is a risk factor for LAM breakthrough, because breakthrough during LAM occurred earlier in patients with this mutation (50 +/- 10 weeks vs. 120 +/- 21 weeks). Because breakthrough on either treatment is frequent for this specific group of patients, the use of combination therapy should be explored.
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Sequence Data
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-
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