title: Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus.
abstract: OBJECTIVE
  We recently identified a polymorphism upstream of interleukin (IL)-28B to be associated with a 2-fold difference in sustained virologic response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment virologic response and SVR.
  
  
  METHODS
  HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid virologic response (RVR, week 4), complete early virologic response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116).
  
  
  RESULTS
  In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P < .0001), complete early virologic response (87% vs 38% and 28%; P < .0001), and SVR (69% vs 33% and 27%; P < .0001) compared with CT and TT. A similar association occurred within African Americans and Hispanics. In a multivariable regression model, CC IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1-6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P < .0001).
  
  
  CONCLUSIONS
  In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and sustained virologic response and effectively predicts treatment outcome.
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muir
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.forename: Dongliang
authors.initials: D
authors.lastname: Ge
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Thomas
authors.initials: T
authors.lastname: Urban
authors.forename: Nezam H
authors.initials: NH
authors.lastname: Afdhal
authors.forename: Ira M
authors.initials: IM
authors.lastname: Jacobson
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lawitz
authors.forename: Jonathan
authors.initials: J
authors.lastname: McCone
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Greg W
authors.initials: GW
authors.lastname: Galler
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Robert
authors.initials: R
authors.lastname: Reindollar
authors.forename: John W
authors.initials: JW
authors.lastname: King
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Kwo
authors.forename: Reem H
authors.initials: RH
authors.lastname: Ghalib
authors.forename: Bradley
authors.initials: B
authors.lastname: Freilich
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Nyberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: David M
authors.initials: DM
authors.lastname: Vock
authors.forename: Karen S
authors.initials: KS
authors.lastname: Pieper
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: Hans L
authors.initials: HL
authors.lastname: Tillmann
authors.forename: Stephanie
authors.initials: S
authors.lastname: Noviello
authors.forename: Kenneth
authors.initials: K
authors.lastname: Koury
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Pedicone
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Brass
authors.forename: Janice K
authors.initials: JK
authors.lastname: Albrecht
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda