title: IL28B polymorphisms predict reduction of HCV RNA from the first day of therapy in chronic hepatitis C.
abstract: OBJECTIVE
  Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-α/ribavirin therapy of chronic hepatitis C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a function of IL28B SNPs.
  
  
  METHODS
  IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242 HCV treatment-naïve Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-α2a (180 μg weekly) and ribavirin (1000-1200 mg daily) with serial HCV-RNA quantifications. Associations between IL28B polymorphisms and early viral kinetics were assessed, accounting for relevant covariates.
  
  
  RESULTS
  In the multivariate analyses for genotype 1 patients, the T allele of rs12979860 (T(rs12979860)) was an independent risk factor for a less pronounced first phase HCV RNA decline (log(10) 0.89IU/ml among T carriers vs. 2.06 among others, adjusted p < 0.001) and lower rapid (15% vs. 38%, adjusted p = 0.007) and sustained viral response rates (48% vs. 66%, adjusted p < 0.001). In univariate analyses, T(rs12979860) was also associated with a reduced second phase decline (p = 0.002), but this association was no longer significant after adjustment for the first phase decline (adjusted p = 0.8). In genotype 2/3 patients, T(rs12979860) was associated with a reduced first phase decline (adjusted p = 0.04), but not with a second phase decline.
  
  
  CONCLUSIONS
  Polymorphisms in IL28B are strongly associated with the first phase viral decline during peginterferon-α/ribavirin therapy of chronic HCV infection, irrespective of HCV genotype.
authors.affiliation: Service of Infectious Diseases, Department of Medicine, University Hospital and University of Lausanne, Switzerland. pierre-yves.bochud@chuv.ch
authors.forename: P-Y
authors.initials: PY
authors.lastname: Bochud
authors.forename: S
authors.initials: S
authors.lastname: Bibert
authors.forename: F
authors.initials: F
authors.lastname: Negro
authors.forename: B
authors.initials: B
authors.lastname: Haagmans
authors.forename: A
authors.initials: A
authors.lastname: Soulier
authors.forename: C
authors.initials: C
authors.lastname: Ferrari
authors.forename: G
authors.initials: G
authors.lastname: Missale
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
authors.forename: J-M
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: S
authors.initials: S
authors.lastname: Schalm
authors.forename: K
authors.initials: K
authors.lastname: Hellstrand
authors.forename: A U
authors.initials: AU
authors.lastname: Neumann
authors.forename: M
authors.initials: M
authors.lastname: Lagging
mesh_terms: D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D013997:Time Factors; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a