Hepatitis C subtyping assay failure in UK patients born in sub‐Saharan Africa: implications for global treatment and elimination

Adeboyejo, K., King, B. J., Tsoleridis, T., Tarr, A. W., McLauchlan, J. , Irving, W. L., Ball, J. K. and McClure, P. (2023) Hepatitis C subtyping assay failure in UK patients born in sub‐Saharan Africa: implications for global treatment and elimination. Journal of Medical Virology, 95(1), e28178. (doi: 10.1002/jmv.28178) (PMID:36168235)

Abstract

Background and Aims: The newly developed direct-acting antivirals have revolutionized the treatment of chronic hepatitis C virus (HCV), with cure rates as high as 98% in some cohorts. Although genome sequencing has demonstrated that some subtypes of HCV naturally harbor drug resistance associated substitutions (RAS), these are often overlooked as “rarities.” Furthermore, commercial subtyping assays and associated epidemiological findings are skewed towards Western cohorts and whole-genome sequencing can be problematic to deploy without significant infrastructure and training support. We thus aimed to develop a simple, robust and accurate HCV subtyping pipeline, to optimize and streamline molecular detection and sequence-based typing of diverse RAS-containing subtypes. Methods: HCV serum derived from 146 individuals, whose likely source of infection was from sub-Saharan Africa (SSA) was investigated with a novel panel of single round polymerase chain reaction (PCR) assays targeting NS5B and NS5A genomic regions. Virus subtype assignments were determined by pairwise-distance analysis and compared to both diagnostic laboratory assignments and free-to-use online typing tools. Results: Partial NS5A and NS5B sequences were respectively obtained from 131 to 135 HCV-positive patients born in 19 different countries from SSA but attending clinics in the UK. We determined that routine clinical diagnostic methods incorrectly subtyped 59.0% of samples, with a further 6.8% incorrectly genotyped. Of five commonly used online tools, Geno2Pheno performed most effectively in determining a subtype in agreement with pairwise distance analysis. Conclusion: This study provides a simple low-cost pathway to accurately subtype in SSA, guide regional therapeutic choice and assist global surveillance and elimination initiatives.

• Item Type: Articles
• Additional Information: K. A. was supported by the Tertiary Education Trust Fund and the National Institute for Health Research Nottingham Biomedical Research Centre.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McLauchlan, Professor John

Creator Roles

McLauchlan, J.: Resources, Project administration

• Authors: Adeboyejo, K., King, B. J., Tsoleridis, T., Tarr, A. W., McLauchlan, J., Irving, W. L., Ball, J. K., and McClure, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Journal of Medical Virology
• Publisher: Wiley
• ISSN: 0146-6615
• ISSN (Online): 1096-9071
• Published Online: 27 September 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Journal of Medical Virology 95(1): e28178
• Publisher Policy: Reproduced under a Creative Commons License