Clinical evaluation of a Hepatitis C Virus whole-genome sequencing pipeline for genotyping and resistance testing

STOP-HCV Consortium

Research output: Contribution to journalArticlepeer-review


Objectives: We sought to evaluate clinically a hepatitis C virus (HCV) whole-genome, next-generation sequencing (NGS) pipeline that is agnostic to viral genotype. Methods: Performance of the NGS pipeline was assessed through comparison of results with Sanger sequencing (SS) of partial HCV genomes. Results: There was 98.7% (376/381) concordance for viral subtype between SS and NGS. The positive and negative per cent agreements for determination of resistance-associated substitutions were 97.8% (95% CI 92.5–99.4%) and 99.9% (95% CI 99.5–100.0%), respectively. The NGS pipeline was also able to detect novel subtypes, mixtures, recombinants, transiently occurring resistance mutations and distinguish re-infection with the same subtype from relapse. Discussion: Particular scenarios where NGS may be used include settings without universal access to pan-genotypic antiviral regimens, those infected with a ‘rare’ subtype or who have been failed by first-line therapy, and in cases of suspected re-infection.

Original languageEnglish
JournalClinical Microbiology and Infection
Publication statusAccepted/In press - 2021

Bibliographical note

Funding Information:
The authors wish to acknowledge the role of HCV Research UK (funded by the Medical Research Foundation ; award number C0365) in collecting and making available data and samples used in the generation of this publication.

Funding Information:
This work was funded by Public Health England and a grant from the Medical Research Council MR/K01532X/1 to the STOP-HCV consortium (Stratified Medicine to Optimize patient outcome with HCV infection). The authors do not have an association that might pose a conflict of interest.

Publisher Copyright:
© 2021


  • Clinical evaluation
  • Genotyping
  • Hepatitis C virus (HCV)
  • Resistance testing
  • Whole-genome sequencing


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