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Basic Characteristics of Mutations
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Mutation Site
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P32L |
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Mutation Site Sentence
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Eight patients had coexisting NS5A RASs of Q24, L28 and/or R30, L31, or Y93 and one patient had coexisting NS5A RASs of P32L and A92K. |
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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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NS5A |
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Standardized Encoding Gene
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NS5A
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Genotype/Subtype
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1 |
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Viral Reference
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AJ238799
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Functional Impact and Mechanisms
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Disease
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HCV 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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Y |
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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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29856885
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Title
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The co-existence of NS5A and NS5B resistance-associated substitutions is associated with virologic failure in Hepatitis C Virus genotype 1 patients treated with sofosbuvir and ledipasvir
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Author
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Mawatari S,Oda K,Tabu K,Ijuin S,Kumagai K,Fujisaki K,Hashiguchi M,Inada Y,Uto H,Hiramine Y,Kure T,Hori T,Taniyama O,Kasai A,Tamai T,Moriuchi A,Ido A
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Journal
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PloS one
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Journal Info
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2018 Jun 1;13(6):e0198642
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Abstract
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OBJECTIVE: The present study aimed to reveal the factors associated with virologic failure in sofosbuvir and ledipasvir (SOF/LDV)-treated patients, and identify baseline NS5A or NS5B resistance-associated substitutions (RASs). METHODS: Four hundred ninety-three patients with Hepatitis C Virus (HCV) genotype 1b infection were treated with SOF/LDV; 31 had a history of interferon (IFN)-free treatment with daclatasvir and asunaprevir. The effect of baseline RASs on the response to SOF/LDV therapy was analyzed. RESULTS: Overall, a sustained virologic response at 12 weeks (SVR12) was achieved in 476 patients (96.6%). The SVR12 rates in the patients with IFN-free treatment-naive and retreatment were 97.6% and 80.6%, respectively. HCV elimination was not achieved in 17 patients, 11 (including 5 with IFN-free retreatment) of whom had virologic failure. Eight patients had coexisting NS5A RASs of Q24, L28 and/or R30, L31, or Y93 and one patient had coexisting NS5A RASs of P32L and A92K. Interestingly, 10 and 8 patients had NS5B A218S and C316N RAS respectively. According to a multivariate analysis, coexisting NS5A RASs, NS5A P32 RAS, NS5B A218 and/or C316 RASs, and gamma-glutamyltranspeptidase were associated with virologic failure. In the naive patients, all patients without NS5B A218 and/or C316 RAS achieved an SVR12. Notably, the SVR12 rates of patients with coexisting NS5A and NS5B RASs were significantly lower (83.3%). CONCLUSIONS: Although SOF/LDV therapy resulted in a high SVR12 rate, coexisting NS5A and NS5B RASs were associated with virologic failure. These results might indicate that the coexisting baseline RASs influence the therapeutic effects of SOF/LDV.
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Sequence Data
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-
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