title: The influence of single and combined IL28B polymorphisms on response to treatment of chronic hepatitis C.
abstract: BACKGROUND
  Three single nucleotide polymorphisms (SNPs) near IL28B gene were shown to be highly predictive of sustained virological response (SVR) in patients with chronic hepatitis C virus (HCV) infection.
  
  
  OBJECTIVE
  This study attempted to demonstrate the role of single and combined IL28B polymorphisms (rs8099917, rs12979860 and rs12980275) and other host and viral factors in predicting response to treatment, in Caucasian patients infected with HCV genotype 1.
  
  
  METHODS
  The IL28B genotypes at 3 SNPs were determined in 106 patients who underwent standard 48-week therapy and out of which 55.7% achieved SVR.
  
  
  RESULTS
  Patients carrying genotypes CCrs12979860 or AArs12980275 were 3.5 and 3 times more likely to achieve SVR, respectively. Genotypes GGrs8099917 and TTrs12979860 were identified as predictors of treatment failure. The presence of IL28B profiles including at least one of the favourable genotypes was identified as the most important factor associated with SVR, followed by younger age and lower grade of histological activity. Of all patients who achieved SVR, 88.1% was carrying one of these IL28B profiles. The strongest PPV of single SNPs for achieving SVR was observed for CCrs12979860 (76.9%). The presence of GGrs8099917 showed the strongest NPV of 85.7%. The correlation of SNPs with other host and viral factors revealed association of TTrs8099917 and lower AST levels.
  
  
  CONCLUSIONS
  Results of this study confirm that all investigated IL28B polymorphisms are associated with treatment response and that presence of any of the favourable IL28B genotypes can be considered independent pretreatment determinant of the effectiveness of therapy.
authors.affiliation: University of Belgrade, Faculty of Medicine, Belgrade, Serbia. ilazarevic@med.bg.ac.rs
authors.forename: Ivana
authors.initials: I
authors.lastname: Lazarevic
authors.forename: Jelena
authors.initials: J
authors.lastname: Djordjevic
authors.forename: Maja
authors.initials: M
authors.lastname: Cupic
authors.forename: Danijela
authors.initials: D
authors.lastname: Karalic
authors.forename: Dragan
authors.initials: D
authors.lastname: Delic
authors.forename: Neda
authors.initials: N
authors.lastname: Svirtlih
authors.forename: Jasmina
authors.initials: J
authors.lastname: Simonovic
authors.forename: Petar
authors.initials: P
authors.lastname: Svorcan
authors.forename: Natasa
authors.initials: N
authors.lastname: Milic
authors.forename: Tanja
authors.initials: T
authors.lastname: Jovanovic
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016896:Treatment Outcome; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Hepatitis C virus (HCV); IL28B; Single nucleotide polymorphism (SNP); Sustained virological response (SVR)