title: Limited use of interleukin 28B in the setting of response-guided treatment with detailed on-treatment virological monitoring.
abstract: A single-nucleotide polymorphism upstream of the interleukin-28B (IL28B) gene is associated with pegylated interferon-alfa-induced viral clearance in hepatitis C virus (HCV) genotype 1 patients. Using a well-characterized cohort of patients randomized to standard versus response-guided therapy, we studied whether the favorable CC type allows shortening of treatment duration. Association with viral kinetics, sustained viral response (SVR), and predictors of response were also analyzed. In the original study, 696 patients were randomized to either standard or variable therapy of 24, 48, or 72 weeks according to first undetectable HCV RNA. Association between IL28B determined by genotyping rs12979860 and end of treatment response and SVR by treatment arm was tested; baseline predictors of response were analyzed using multiple logistic regression. A total of 454 patients were evaluated. The frequency of IL28B type was CC = 29%, CT = 53%, TT = 18%. CC type was strongly associated with rapid virological response (RVR) as well as higher rates of week 8 and week 12 response. CC type was associated with SVR in both arms. In patients with RVR, SVR was high and IL28B type was not associated with SVR. In RVR patients, there was no significant difference in SVR or relapse rates after 24 or 48 weeks by IL28B type. Among non-RVR patients, CC type was associated with SVR at a higher rate than CT/TT, both in standard and variable analysis. However, when week 8 and week 12 responders were considered separately, IL28B type was no longer predictive of SVR. Few CC patients remained viremic beyond week 8 to allow the analysis of relationships between IL28B type and extended treatment.
  
  
  CONCLUSIONS
  In HCV-1 patients, the favorable CC type strongly predicted higher rates of on-treatment virological milestones and SVR. However, achievement of on-treatment virological milestones was the critical factor in determining outcome. IL28B type appeared to have limited potential for response-guided treatment strategies.
authors.affiliation: Liver Unit, Istituto 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: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Nicola
authors.initials: N
authors.lastname: Minerva
authors.forename: Daniela
authors.initials: D
authors.lastname: Petruzzellis
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mottola
authors.forename: Donato
authors.initials: D
authors.lastname: Bacca
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C000624353:interferon-lambda, human; D000095022:Interferon Lambda