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

J Hepatol. 2017 Oct;67(4):680-686. doi: 10.1016/j.jhep.2017.05.027. Epub 2017 Jun 13.


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.

Keywords: Chimeras; DAA-treatment; Epidemiology; HCV genotype; Phylogeny; SVR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Antiviral Agents / therapeutic use
  • Chimera / genetics
  • Drug Resistance, Viral / genetics
  • Evolution, Molecular
  • Genotype
  • Germany / epidemiology
  • Hepacivirus / classification
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / epidemiology
  • Hepatitis C, Chronic / virology*
  • Humans
  • Israel / epidemiology
  • Italy / epidemiology
  • Molecular Epidemiology
  • Phylogeny
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Reassortant Viruses / drug effects
  • Reassortant Viruses / genetics
  • Recombination, Genetic
  • Sustained Virologic Response


  • Antiviral Agents