title: Prevalence of the hepatitis C virus NS3 polymorphism Q80K in genotype 1 patients in the European region.
abstract: Hepatitis C virus (HCV) NS3 polymorphism Q80K is mainly found in patients with HCV genotype (G) 1a, and has been associated with a reduced treatment response to simeprevir with pegylated interferon (P) and ribavirin (R). Prevalence of Q80K among G1 patients may vary geographically. Q80K prevalence in the North-American G1 population in a recent study was 34%. We conducted a post hoc meta-analysis of Q80K polymorphism prevalence among HCV G1-infected patients enrolled in simeprevir and telaprevir Phase II/III studies. Baseline HCV NS3/4A protease sequences were analysed by population sequencing to determine Q80K prevalence. Overall, of 3349 patients from 25 countries in the European region analysed, 35.8%, 63.8% and 0.3% of patients had G1a, G1b and other/unknown HCV G1 subtypes, respectively. Q80K was detected at baseline in 7.5% of HCV G1 patients overall. Examination by subtype showed that 19.8%, 0.5% and 18.2% of patients with G1a, G1b and other/unknown HCV G1 subtypes had the Q80K polymorphism, respectively. Among countries in the European region with sequencing data available for either ⩾20 patients with G1a and/or ⩾40 G1 patients overall, the Q80K prevalence in G1 ranged from 0% in Bulgaria to 18.2% in the UK. Q80K prevalence also varied within G1a across different countries. HCV subtype 1a was correctly determined in 99% of patients by the LiPA v2 assay. A low overall prevalence of Q80K was observed in HCV G1-infected patients in the European region, compared with North America. However, the prevalence varied by country, due to differing ratios of G1a/G1b and differing Q80K prevalence within the G1a populations.
authors.affiliation: Johann Wolfgang Goethe University Hospital, Medical Department 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: sarrazin@em.uni-frankfurt.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: elathouw@its.jnj.com.
authors.forename: Erkki
authors.initials: E
authors.lastname: Lathouwers
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: mpeeter7@its.jnj.com.
authors.forename: Monika
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: bdaems1@its.jnj.com.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Daems
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: abuelens@its.jnj.com.
authors.forename: Annemie
authors.initials: A
authors.lastname: Buelens
authors.affiliation: Janssen Research & Development LLC, 1125 Trenton Harbourton Rd, Titusville, NJ 08560, United States. Electronic address: jwitek@its.jnj.com.
authors.forename: James
authors.initials: J
authors.lastname: Witek
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: YWyckma1@its.jnj.com.
authors.forename: Yves
authors.initials: Y
authors.lastname: Wyckmans
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: bfevery@its.jnj.com.
authors.forename: Bart
authors.initials: B
authors.lastname: Fevery
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: tverbinn@its.jnj.com.
authors.forename: Thierry
authors.initials: T
authors.lastname: Verbinnen
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: aghys@its.jnj.com.
authors.forename: Anne
authors.initials: A
authors.lastname: Ghys
authors.affiliation: Janssen-Cilag, Vorgartenstraße 206B, 1020 Vienna, Austria. Electronic address: mschlag@its.jnj.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Schlag
authors.affiliation: Janssen Cilag, 1 Rue Camille Desmoulins, 92130 Issy-les-Moulineaux, France. Electronic address: abaldini@its.jnj.com.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baldini
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: sdmeyer@its.jnj.com.
authors.forename: Sandra
authors.initials: S
authors.lastname: De Meyer
authors.affiliation: Janssen Infectious Diseases BVBA, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: olenz@its.jnj.com.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D005060:Europe / Q000453:epidemiology; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D009656:North America / Q000453:epidemiology; D009842:Oligopeptides / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D017422:Sequence Analysis, DNA; D000069616:Simeprevir / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D000069616:Simeprevir; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C486464:telaprevir
keywords: Hepatitis C; NS3/4A protease; Prevalence; Q80K polymorphism; Simeprevir; Virology