title: Identification of naïve HVC-4 patients who may be treated with pegylated-interferon and ribavirin according to IL28B polymorphisms.
abstract: BACKGROUND
  The current treatment of HCV-4 patients is dual therapy with PEG-IFN and ribavirin; however, new drugs against this genotype will be available within few months. Despite the evidenced good virological response in IFN-free regimens, the high cost of these new therapies will require patient selection. In our paper we propose the use of both rs8099917 and rs12979860 IL28-B polymorphisms, in order to identify potentially categories of SVR, null-responder and relapse and consequently to choose the dual therapy or novel approach.
  
  
  METHODS
  One hundred and sixty-nine patients with chronic hepatitis C and genotype 4 treated with pegylated interferon and ribavirin for 48weeks were retrospectively studied. All patients were genotyped for rs8099917 and rs12979860 interleukin-28B polymorphisms.
  
  
  RESULTS
  80 patients with SVR (88.8%) had the TT/CC or TT/TC (rs8099917/rs12979860) (p<0.001) genotypes; the null-responders (n=13), 9 (69.2%) showed the GG/TT allelic distribution (p<0.001); relapsers showed a prevalent distribution of the TG/TC genotype (83.3%) (p<0.001). The 6 (100%) breakthrough patients showed TT/TC genotype, while the partial responders patients did not show any particular IL-28B genetic profile. Genetic profiles different from TT/CC showed 94.9% negative predictive value for SVR, with 92.6% of sensitivity and 65.2% of specificity. Insulin-resistance, diabetes and liver fibrosis were not relevant in our multivariate analysis.
  
  
  CONCLUSIONS
  The combination of both rs8099917/rs12979860 polymorphisms is useful for early identification of SVR, null-responders and relapsers. This could be used to chose between standard dual therapy or novel approach with IFN-free regimens.
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy. Electronic address: lucio.boglione@unito.it.
authors.forename: Lucio
authors.initials: L
authors.lastname: Boglione
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cusato
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: De Nicolò
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cariti
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Allegra
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ghisetti
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
mesh_terms: D000328:Adult; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Breakthrough; Genetic polymorphisms; HCV-4; IL-28B; Null responder; Relapser