Origin, prevalence and response to therapy of hepatitis C virus genotype 2k/1b chimeras

Simone Susser, Julia Dietz, Bernhard Schlevogt, Eli Zuckerman, Mira Barak, Valeria Piazzolla, Anita Howe, Holger Hinrichsen, Sandra Passmann, Rasha Daniel, Markus Cornberg, Alessandra Mangia, Stefan Zeuzem, Christoph Sarrazin

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims Little is known about the epidemiology and frequency of recombinant HCV genotype 2/1 strains, which may represent a challenge for direct antiviral therapy (DAA). This study aims to identify the epidemiology and phylogeny of HCV genotype 2/1 strains and encourages genotype screening, to select the DAA-regimen that achieves the optimal sustained virologic response. Methods Consecutive samples from HCV genotype 2 infected patients, according to commercial genotyping, from Germany, Italy and Israel were re-genotyped by Sanger-based sequencing. Virologic, epidemiological, and phylogenetic analyses including other published chimeras were performed. Results Sequence analysis of 442 supposed HCV genotype 2 isolates revealed 61 (genotype 2k/1b (n = 59), 2a/1b (n = 1) or 2b/1a (n = 1)) chimeras. No chimeras were observed in Italy, but the frequency was 14% and 25% in Germany and Israel. Treatment of viral chimera with sofosbuvir/ribavirin led to virologic relapse in 25/27 patients (93%). Nearly all patients treated with genotype 1-based DAA-regimens initially (n = 8/9), or after relapse (n = 13/13), achieved a sustained virologic response. Most patients with 2k/1b chimeras (88%) were originally from eight different areas of the former Soviet Union. All known 2k/1b chimeras harbour the same recombination breakpoint and build one phylogenetic cluster, while all other chimeras have different phylogenies. Conclusions The HCV genotype 2k/1b variant derives from one single recombination event most likely in the former Soviet Union, while other chimeras are unique and develop independently. A relatively high frequency has been observed along the migration flows, in Germany and Israel. In countries with little migration from the former Soviet Union the prevalence of 2k/1b chimeras is expected to be low. Treatment with sofosbuvir plus ribavirin is insufficient, but genotype 1-based regimens seem to be effective. Lay summary: The frequency of recombinant HCV is higher than expected. A novel recombinant variant (HCV genotype 2a/1b) was identified. Screening for recombinant viruses would contribute to increased response rates to direct antiviral therapy.

Original languageEnglish
Pages (from-to)680-686
Number of pages7
JournalJournal of Hepatology
Volume67
Issue number4
DOIs
Publication statusPublished - Oct 1 2017

Keywords

  • Chimeras
  • DAA-treatment
  • Epidemiology
  • HCV genotype
  • Phylogeny
  • SVR

ASJC Scopus subject areas

  • Hepatology

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