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Basic Characteristics of Mutations
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Mutation Site
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Y93H |
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Mutation Site Sentence
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Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. |
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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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1b |
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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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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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- |
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Treatment
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- |
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Location
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Belgium;France;Germany;Hungary;Spain;United Kingdom |
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Literature Information
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PMID
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28135777
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Title
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Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naive patients with hepatitis C virus genotype 1b and advanced liver disease
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Author
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Hezode C,Almasio PL,Bourgeois S,Buggisch P,Brown A,Diago M,Horsmans Y,Serfaty L,Szalay F,Gaeta GB,Planas R,Schlag M,Lonjon-Domanec I,Omoruyi E,DeMasi R,Zeuzem S
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Journal
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Liver international : official journal of the International Association for the Study of the Liver
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Journal Info
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2017 Sep;37(9):1304-1313
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Abstract
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BACKGROUND & AIMS: We investigated the efficacy and safety of simeprevir plus daclatasvir in treatment-naive patients with chronic, genotype 1b hepatitis C virus infection and advanced liver disease, excluding patients with pre-defined NS5A resistance-associated substitutions. METHODS: This phase II, open-label, single-arm, multicentre study included patients aged >/=18 years with advanced fibrosis or compensated cirrhosis (METAVIR F3/4). Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. Simeprevir (150 mg)+daclatasvir (60 mg) once daily was administered for 12 or 24 weeks; treatment could be extended to 24 weeks prior to or at the Week 12 visit. Primary efficacy endpoint was sustained virological response 12 weeks after the end of treatment. RESULTS: A total of 106 patients were treated; 27% patients were aged >65 years, 39% had cirrhosis, 53% had estimated glomerular filtration rate 30-89 mL/min, 14% had diabetes, and 38% had arterial hypertension. Overall, 42/106 received 12 weeks of treatment and 64/106 received 24 weeks of treatment. Ninety-seven (92%) patients achieved a sustained virological response 12 weeks after the end of treatment. The reasons for failure were viral breakthrough (n=7) at weeks 4-16, early treatment discontinuation (n=1) and viral relapse (n=1). Seventy-four (70%) patients had >/=1 adverse event during treatment, including six (6%) patients with >/=1 serious adverse event. Three (3%) patients discontinued treatment owing to adverse events. CONCLUSIONS: Simeprevir+daclatasvir demonstrated strong antiviral activity and was well-tolerated in patients with hepatitis C virus genotype 1b infection, advanced liver disease and a high prevalence of comorbidities. However, viral breakthrough occurred in seven patients, making this regimen unsatisfactory.
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Sequence Data
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-
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