Prevalence of mixed genotype hepatitis C virus infections in the UK as determined by genotype‐specific PCR and deep sequencing

McNaughton, A.L., Sreenu, V.B. , Wilkie, G., Gunson, R., Templeton, K. and Leitch, E.C.M. (2018) Prevalence of mixed genotype hepatitis C virus infections in the UK as determined by genotype‐specific PCR and deep sequencing. Journal of Viral Hepatitis, 25(5), pp. 524-534. (doi: 10.1111/jvh.12849) (PMID:29274184) (PMCID:PMC5947153)

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Abstract

The incidence of mixed genotype hepatitis C virus infections in the UK is largely unknown. As the efficacy of direct acting antivirals is variable across different genotypes, treatment regimens are tailored to the infecting genotype, which may pose issues for the treatment of underlying genotypes within undiagnosed mixed genotype HCV infections. There is therefore a need to accurately diagnose mixed genotype infections prior to treatment. PCR-based diagnostic tools were developed to screen for the occurrence of mixed genotype infections caused by the most common UK genotypes, 1a and 3, in a cohort of 506 individuals diagnosed with either of these genotypes. The overall prevalence rate of mixed infection was 3.8% however this rate was unevenly distributed, with 6.7% of individuals diagnosed with genotype 3 harbouring genotype 1a strains and only 0.8% of samples from genotype 1a patients harbouring genotype 3 (p<0.05). Mixed infection samples consisted of a major and a minor genotype, with the latter constituting less than 21% of the total viral load and, in 67% of cases, less than 1% of the viral load. Analysis of a subset of the cohort by Illumina PCR-next generation sequencing resulted in a much greater incidence rate than obtained by PCR. This may have occurred due to the non-quantitative nature of the technique and despite the designation of false positive thresholds based on negative controls.

Item Type:Articles
Keywords:Direct acting antivirals, HCV genotyping, hepatitis C virus, mixed genotype HCV infections, next generation sequencing.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilkie, Dr Gavin and Vattipally, Dr Sreenu and Leitch, Dr Carol
Authors: McNaughton, A.L., Sreenu, V.B., Wilkie, G., Gunson, R., Templeton, K., and Leitch, E.C.M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Viral Hepatitis
Publisher:Wiley
ISSN:1352-0504
ISSN (Online):1365-2893
Published Online:23 December 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Journal of Viral Hepatitis 25(5):524-534
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
501442Centre for Integrated VirologyMassimo PalmariniMedical Research Council (MRC)G0801822MVLS III - CENTRE FOR VIRUS RESEARCH