title: Predicting response to therapy in chronic hepatitis C: an approach combining interleukin-28B gene polymorphisms and clinical data.
abstract: OBJECTIVE
  Polymorphisms at the interleukin-28B (IL28B) gene predict therapeutic response in chronic hepatitis C virus genotype 1 (CHC-1) infection. The aim of the present study was to establish whether a unique single-nucleotide polymorphism (SNP) represents the whole predictive value of the IL28B haplotype for sustained viral response (SVR) and primary non-response (PNR).
  
  
  METHODS
  SNP rs12979860 and rs8099917 were determined by TaqMan assays in 110 CHC-1 Caucasian patients treated with pegylated interferon plus ribavirin.
  
  
  RESULTS
  There were 51 SVR, 43 PNR, and 16 relapses. Baseline predictors of SVR were rs12979860CC genotype (P = 0.008), viral load < 400.000 IU/mL (P < 0.010), age (P = 0.013), γ-glutamyl transferase (P = 0.022), alkaline phosphatase (P = 0.008), and cholesterol (P = 0.048). The area under the receiver-operating curve (AUROC) of the model, including these variables, was 0.841 (95% confidence interval [CI] = 0.767-0.916). The same figures for PNR were rs12979860 T-allele carrier state (P = 0.00008), viral load ≥ 400.000 IU/mL (P = 0.007), aspartate aminotransferase/alanine aminotransferase (P = 0.048), and serum cholesterol (P = 0.064), (AUROC = 0.869, 95% CI = 0.792-0.945). After excluding rs12979860CT SNP from multivariate analyses, the rs8099917 genotype alone did not predict SVR (P = 0.185), but strongly predicted PNR (P = 0.003). The significance of haplotypes combining both SNP as predictors of SVR and PNR was higher than those of each separate SNP.
  
  
  CONCLUSIONS
  The rs12979860 SNP strongly predicts therapeutic response in CHC-1 patients, and if associated with easy-to-obtain baseline criteria, provides a useful tool for the selection of candidates for antiviral therapy. IL28B haplotypes might improve the clinical usefulness of individual SNP.
authors: Liver Unit, Service of Gastroenterology, Hospital Clínico San Carlos, and School of Medicine, Complutense University, Madrid, Spain. jladero.hcsc@salud.madrid.org
authors: José M
authors: JM
authors: Ladero
authors: Elena García
authors: EG
authors: Martin
authors: Cristina
authors: C
authors: Fernández
authors: Miguel
authors: M
authors: Carballo
authors: María J
authors: MJ
authors: Devesa
authors: Carmen
authors: C
authors: Martínez
authors: Avelina
authors: A
authors: Suárez
authors: Manuel
authors: M
authors: Díaz-Rubio
authors: José A
authors: JA
authors: Agúndez
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D018579:Patient Selection; D010641:Phenotype; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; 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; C100416:peginterferon alfa-2a