title: Patients eligible for treatment with simeprevir in a French center.
abstract: BACKGROUND
  Simeprevir (Olysio(®)), a second-wave protease inhibitor recently approved for the treatment of chronic hepatitis C, is not indicated in patients with genotype 1a strain harboring the Q80K protease mutation. Phase 2 and 3 studies on this molecule mainly focused on North American patients and the prevalence of Q80K is particularly high in the USA (around 50%). The prevalence of this mutation in other parts of the world is currently unknown.
  
  
  OBJECTIVE
  The purpose of our study was to perform a detection of this mutation in a single PCR technique and to study the prevalence of this Q80K mutation in a non U.S. population. We can thus estimate the proportion of HCV positive patients who can be treated with simeprevir.
  
  
  METHODS
  We conducted a meta-analysis of response rates in the presence or absence of this mutation in randomized trials and then describe a simple and reliable method to detect this mutation. We also examined bilirubin levels in our cohort of 95 HCV genotype 1a patients.
  
  
  RESULTS
  Ten patients (10.5%) had a Q80K mutation and 12 patients exhibited bilirubin levels above the upper limit of normal at baseline. In our cohort, 21 patients (22%) were therefore ineligible for treatment with simeprevir. The prevalence of this mutation seems to be much lower in European patients.
  
  
  CONCLUSIONS
  In conclusion, before considering treatment with simeprevir, physicians must be able to screen for the Q80K mutation.
authors.affiliation: Department of Virology, Amiens University Medical Center, Amiens, France; Virology Research Unit, EA 4294, Jules Verne University of Picardie, Amiens, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Morel
authors.affiliation: Department of Virology, Amiens University Medical Center, Amiens, France; Virology Research Unit, EA 4294, Jules Verne University of Picardie, Amiens, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Duverlie
authors.affiliation: Department of Virology, Amiens University Medical Center, Amiens, France; Virology Research Unit, EA 4294, Jules Verne University of Picardie, Amiens, France. Electronic address: etienne.brochot@u-picardie.fr.
authors.forename: Etienne
authors.initials: E
authors.lastname: Brochot
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005602:France; D005838:Genotype; D016174:Hepacivirus / Q000201:enzymology* / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics; D000069616:Simeprevir; D013449:Sulfonamides / 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; D006575:Heterocyclic Compounds, 3-Ring; D050505:Mutant Proteins; D000069616:Simeprevir; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: HCV treatment; K mutation; Q80; Simeprevir