title: Impact of IL28B gene polymorphisms on interferon-λ3 plasma levels during pegylated interferon-α/ribavirin therapy for chronic hepatitis C in patients coinfected with HIV.
abstract: OBJECTIVE
  The mechanism explaining the strong association between IL28B rs12979860 polymorphisms and treatment outcome in chronic hepatitis C remains unclear. We explore whether IL28B protein [interferon (IFN)-λ3] plasma levels may vary according to IL28B genotype and/or following pegylated IFN-α/ribavirin therapy.
  
  
  METHODS
  A total of 112 HIV/hepatitis C virus (HCV)-coinfected patients who completed a course of pegylated IFN-α/ribavirin therapy were examined. Sustained virological response (SVR) was achieved by 56% of patients. IL28B rs12979860 alleles were genotyped using the 5' nuclease assay with specific TaqMan probes. A specific enzyme immunoassay was used to measure IFN-λ3 plasma levels before initiating anti-HCV therapy and at week 4 of treatment.
  
  
  RESULTS
  No significant differences between CC and non-CC IL28B carriers were found at baseline, either in the proportion of patients with detectable IFN-λ3 plasma levels or in their median values. In contrast, median IFN-λ3 plasma levels at week 4 of therapy significantly increased with respect to baseline in CC carriers [34.3 (16.7-56.3) versus 15.6 (15.6-30.3) pg/mL, respectively; P < 0.0001], but not in CT/TT carriers. Unexpectedly, increases in IFN-λ3 at week 4 of therapy did not predict SVR.
  
  
  CONCLUSIONS
  The exogenous administration of IFN-α may induce IFN-λ3 release in IL28B CC carriers, but not in CT/TT carriers. However, this finding does not account for the link between IL28B polymorphisms and treatment outcome.
authors.affiliation: Infectious Diseases Department, Hospital Carlos III, Madrid, Spain. normaibon@yahoo.com
authors.forename: Norma I
authors.initials: NI
authors.lastname: Rallón
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Susanna
authors.initials: S
authors.lastname: Naggie
authors.forename: Clara
authors.initials: C
authors.lastname: Restrepo
authors.forename: John
authors.initials: J
authors.lastname: McHutchison
authors.forename: Eugenia
authors.initials: E
authors.lastname: Vispo
authors.forename: José M
authors.initials: JM
authors.lastname: Benito
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D016898:Interferon-alpha / Q000008:administration & dosage*; D007372:Interferons; D007378:Interleukins / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012254:Ribavirin / Q000008:administration & dosage*; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda