title: An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response.
abstract: OBJECTIVE
  Polymorphisms in the region of the interleukin (IL)-28B gene on chromosome 19 have been associated with peginterferon-alfa-induced clearance of genotype 1 hepatitis C virus (HCV); there are no data for patients with genotype 2 or 3 HCV. We evaluated the effects of IL-28B polymorphisms on response to treatment with peginterferon and ribavirin in a well-characterized cohort of genotype 2/3 patients.
  
  
  METHODS
  DNA was analyzed from 268 patients (Caucasian: genotype 2, 213; genotype 3, 55). Patients were randomly assigned to groups that received standard duration (24 wk; n = 68) or variable durations of therapy. Patients who received variable durations (VD) and had a rapid virologic response (RVR) were treated for 12 weeks (VD12; n = 122); those without an RVR were treated for 24 weeks (VD24; n = 78). IL-28B genotypes (rs12979860) were analyzed for association with treatment response.
  
  
  RESULTS
  The frequencies of the IL-28B genotypes were as follows: CC, 37%; CT, 48%; and TT, 15%; 82% of patients with the CC genotype achieved a sustained virologic response (SVR), compared with 75% with the CT and 58% with the TT genotypes (P = .0046). Differences between IL-28B genotypes were greatest among patients who failed to attain RVR (VD24 SVR rates: CC, 87%; CT, 67%; and TT, 29%; P = .0002). Among patients with RVRs (61%), the IL-28B genotype was not associated with SVR (>70% for all IL-28B genotypes). In a multivariable logistic regression model, IL-28B genotype predicted SVR (odds ratio, 1.76; 95% confidence interval, 1.16-2.7).
  
  
  CONCLUSIONS
  An IL-28B polymorphism was associated with an SVR in patients infected with genotype 2/3 HCV who did not achieve a RVR. Analysis of IL-28B genotype might be used to guide treatment for these patients.
authors.affiliation: Liver Unit, Instituto di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy. a.mangia@tin.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: Rosanna
authors.initials: R
authors.lastname: Santoro
authors.forename: Valeria
authors.initials: V
authors.lastname: Piazzolla
authors.forename: Hans L
authors.initials: HL
authors.lastname: Tillmann
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mottola
authors.forename: Daniela
authors.initials: D
authors.lastname: Petruzzellis
authors.forename: Donato
authors.initials: D
authors.lastname: Bacca
authors.forename: Vito
authors.initials: V
authors.lastname: Carretta
authors.forename: Nicola
authors.initials: N
authors.lastname: Minerva
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007558:Italy; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; 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; C417083:peginterferon alfa-2b