Hepatitis C virus deep sequencing for sub-genotype identification in mixed infections: A real-life experience
Autor: | José A Del Campo, Josep Quer, Manuel Romero-Gómez, Manuel Parra-Sánchez, Blanca Figueruela, Jose C. Palomares, Samuel Bernal, Josep Gregori, Silvia García-Rey, L. Grande |
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Rok vydání: | 2018 |
Předmět: |
Adult
Male 0301 basic medicine Microbiology (medical) Deep sequencing Genotype Hepatitis C virus Hepacivirus Viral Nonstructural Proteins Biology Direct-acting antivirals medicine.disease_cause Article lcsh:Infectious and parasitic diseases 03 medical and health sciences Genotype 1b medicine Mixed infection Humans lcsh:RC109-216 Genotyping Coinfection food and beverages High-Throughput Nucleotide Sequencing Sequence Analysis DNA General Medicine Hepatitis C Middle Aged Viral Load medicine.disease Virology 030104 developmental biology Infectious Diseases NGS HCV Female Viral load |
Zdroj: | International Journal of Infectious Diseases, Vol 67, Iss C, Pp 114-117 (2018) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona International Journal of Infectious Diseases |
ISSN: | 1201-9712 |
DOI: | 10.1016/j.ijid.2017.12.016 |
Popis: | Highlights • Routine strategies for hepatitis C virus (HCV) genotyping have several limitations. Deep sequencing methods can solve this problem. • Accurate determination of viral genotypes and subtypes would allow optimal patient management and the most effective therapy. • Mixed infections may represent a key factor for efficient therapy. Patients infected with more than one HCV genotype (mixed infection) can be detected only by deep sequencing methods. • These patients can fail treatment with direct-acting antiviral agents, hence next-generation sequencing methods are highly recommended in clinical practice. Background The effectiveness of the new generation of hepatitis C treatments named direct-acting antiviral agents (DAAs) depends on the genotype, subtype, and resistance-associated substitutions present in individual patients. The aim of this study was to evaluate a massive sequencing platform for the analysis of genotypes and subtypes of hepatitis C virus (HCV) in order to optimize therapy. Methods A total of 84 patients with hepatitis C were analyzed. The routine genotyping methodology for HCV used at the study institution (Versant HCV Assay, LiPA) was compared with a deep sequencing platform (454/GS-Junior and Illumina MiSeq). Results The mean viral load in these HCV patients was 6.89 × 106 ± 7.02 × 105. Viral genotypes analyzed by LiPA were distributed as follows: 26% genotype 1a (22/84), 55% genotype 1b (46/84), 1% genotype 1 (1/84), 2.5% genotype 3 (2/84), 6% genotype 3a (5/84), 6% genotype 4a/c/d (5/84). When analyzed by deep sequencing, the samples were distributed as follows: 27% genotype 1a (23/84), 56% genotype 1b (47/84), 8% genotype 3a (7/84), 5% genotype 4d (4/84), 2.5% genotype 4f (2/84). Six of the 84 patients (7%) were infected with more than one subtype. Among these, 33% (2/6) failed DAA-based triple therapy. Conclusions The detection of mixed infection could explain some treatment failures. Accurate determination of viral genotypes and subtypes would allow optimal patient management and improve the effectiveness of DAA therapy. |
Databáze: | OpenAIRE |
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