title: Impact of hepatitis C virus core mutations on the response to interferon-based treatment in chronic hepatitis C.
abstract: OBJECTIVE
  To determine whether hepatitis C virus (HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients.
  
  
  METHODS
  One hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein (BigDye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in hostIL28Bgene rs12979860 (Custom TaqMan 5' allelic discrimination assay; Applied Biosystems).
  
  
  RESULTS
  Of the patients, all were infected with HCV genotype 1b, 44.4% had low baseline HCV viral load, and 37.9% had mild/moderate fibrosis. Only 38.9% achieved therapeutic success, defined as sustained virological response (SVR). Eighty-eight percent of the patients presented at least one substitution at core position 70 (R70Q/H) or/and position 91 (L91M). The favorable IL28B CC polymorphism was detected in only 17.6% of the patients. In the univariate analysis, young age (P< 0.001), urban residence (P= 0.004), IL28B CC genotype (P< 0.001), absence of core mutations (P= 0.005), achievement of rapid virologic response (P< 0.001) and early virological response (P< 0.001) were significantly correlated with SVR. A multivariate analysis revealed three independent predictors of therapeutic success: young age (P< 0.001), absence of core substitutions (P= 0.04) and IL28B CC genotype (P< 0.001); the model correctly classified 75.9% of SVR cases with a positive predictive value of 80.7%.
  
  
  CONCLUSIONS
  HCV core mutations can help distinguish between patients who can still benefit from the affordable IFN-based therapy from those who must be treated with DAAs to prevent the evolution towards end-stage liver disease.
authors.affiliation: Camelia Sultana, Simona Ruta, Virology Discipline, Carol Davila University of Medicine and Pharmacy, 030304 Bucharest, Romania.
authors.forename: Camelia
authors.initials: C
authors.lastname: Sultana
authors.affiliation: Camelia Sultana, Simona Ruta, Virology Discipline, Carol Davila University of Medicine and Pharmacy, 030304 Bucharest, Romania.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Oprişan
authors.affiliation: Camelia Sultana, Simona Ruta, Virology Discipline, Carol Davila University of Medicine and Pharmacy, 030304 Bucharest, Romania.
authors.forename: Monica Delia
authors.initials: MD
authors.lastname: Teleman
authors.affiliation: Camelia Sultana, Simona Ruta, Virology Discipline, Carol Davila University of Medicine and Pharmacy, 030304 Bucharest, Romania.
authors.forename: Sorin
authors.initials: S
authors.lastname: Dinu
authors.affiliation: Camelia Sultana, Simona Ruta, Virology Discipline, Carol Davila University of Medicine and Pharmacy, 030304 Bucharest, Romania.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Oprea
authors.affiliation: Camelia Sultana, Simona Ruta, Virology Discipline, Carol Davila University of Medicine and Pharmacy, 030304 Bucharest, Romania.
authors.forename: Mihai
authors.initials: M
authors.lastname: Voiculescu
authors.affiliation: Camelia Sultana, Simona Ruta, Virology Discipline, Carol Davila University of Medicine and Pharmacy, 030304 Bucharest, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Ruta
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005838:Genotype; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D014758:Viral Core Proteins / Q000235:genetics*; D044465:White People; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D014758:Viral Core Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a
keywords: Caucasian patients; Chronic hepatitis C; Core substitutions; IL28B polymorphism; Treatment