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Basic Characteristics of Mutations
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Mutation Site
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L31M |
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Mutation Site Sentence
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Subtype 2m naturally carries the NS5A L31M RAS. |
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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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2m |
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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 C, 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
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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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33208686
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Title
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Real-world efficacy and safety of direct-acting antiviral drugs in patients with chronic hepatitis C and inherited blood disorders
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Author
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Ruiz I,Fourati S,Ahmed-Belkacem A,Rodriguez C,Scoazec G,Donati F,Soulier A,Demontant V,Poiteau L,N'Debi M,Francois M,Chevaliez S,Pawlotsky JM
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Journal
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European journal of gastroenterology & hepatology
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Journal Info
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2021 Dec 1;33(1S Suppl 1):e191-e196
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Abstract
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BACKGROUND: Patients with inherited blood disorders (IBLD) have a high risk of hepatitis C virus (HCV) infection. The aim of this work was to assess the efficacy and safety of HCV direct-acting antiviral (DAA)-based treatment in patients with IBLD and chronic HCV infection. METHODS: Twenty-seven patients (25 with sickle cell disease, 1 with beta-thalassemia and 1 with hemoglobin D-Punjab), including 3 with compensated cirrhosis, were included. They were treated with sofosbuvir in combination with ribavirin, daclatasvir, ledipasvir, or velpatasvir or with grazoprevir/elbasvir for 8 or 12 weeks. In the case of treatment failure, in-vitro assessment of resistance-associated substitutions (RASs) and full-length genome sequence analysis by means of deep sequencing were performed. RESULTS: Treatment was safe and well-tolerated and there were no drug discontinuations due to DAA-related adverse events. Twenty-five out of the 27 patients (93%) achieved sustained virological response 12 weeks post-treatment. One patient discontinued after 18 days due to adverse events unrelated to the antiviral treatment. One patient infected with 'unusual' genotype 2 subtype 2m relapsed. Subtype 2m naturally carries the NS5A L31M RAS. In a genotype 2a subgenomic replicon model, L31M increased daclatasvir effective concentration 50% (EC50) by 97-fold, but velpatasvir EC50 by only 3-fold, without altering the replication capacity. This patient was successfully retreated with sofosbuvir/velpatasvir for 12 weeks. CONCLUSION: DAA-based regimens are well tolerated and highly efficacious in patients with chronic hepatitis C and IBLD in the real-world setting. Thus, DAA-based antiviral treatment should be prioritized in this thus far neglected population of HCV-infected patients.
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Sequence Data
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-
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