title: Importance of host genetic factors HLA and IL28B as predictors of response to pegylated interferon and ribavirin.
abstract: OBJECTIVE
  Viral factors are considered the best predictors of response to treatment for chronic hepatitis C (CHC), but genetic factors are known to have an important role in this respect. This paper investigates the relationships among the host genetic factors HLA and IL28B, viral factors, and the outcome of combination therapy.
  
  
  METHODS
  A multicenter retrospective cohort of 428 previously untreated CHC patients was treated with pegylated interferon/ribavirin (pegIFN/RBV) for 48 weeks. In all, 378 (88%) of these patients were genotype 1 or 4, and 50 (12%) were genotype 2 or 3.
  
  
  RESULTS
  Multivariate logistic regression showed the rs12979860 CC genotype (adjusted odds ratio (aOR)=4.3, 95% confidence interval (95% CI): 2.6-7), the HLA-DQB1*0301 allele (aOR=2.08, 95% CI: 1.2-3.5) and age, viral genotype, and viral load levels to be significantly associated with sustained virological response (SVR). When the variable rs12979860 was eliminated, the area under the receiver operating characteristic (ROC) curve (AUC) decreased significantly (0.76 vs. 0.69; P=0.03). AUC values derived from viral factors were lower than those corresponding to host genetic factors (0.67 vs. 0.72, respectively; P=0.04). The HLA-DQB1*0301 and A*0201 alleles were associated with rs12979860 CC genotype and SVR (P<0.0001).
  
  
  CONCLUSIONS
  The HLA-DQB1*0301 allele and IL28B genotype are factors that are associated independently with SVR. There is a synergism between the HLA-DQB1*0301 and HLA-A*0201 alleles with polymorphism rs12979860 CC, which increases the SVR rate. IL28B genotype is the best predictor of SVR.
authors.affiliation: Unidad de Aparato Digestivo, Hospital Universitario San Cecilio, Granada, Spain. palomalancha@hotmail.com
authors.forename: Paloma Muñoz
authors.initials: PM
authors.lastname: de Rueda
authors.forename: Miguel-Ángel
authors.initials: MÁ
authors.lastname: López-Nevot
authors.forename: Pablo
authors.initials: P
authors.lastname: Sáenz-López
authors.forename: Jorge
authors.initials: J
authors.lastname: Casado
authors.forename: Antonia
authors.initials: A
authors.lastname: Martín-Casares
authors.forename: Pablo
authors.initials: P
authors.lastname: Palomares
authors.forename: Rosa
authors.initials: R
authors.lastname: Quiles
authors.forename: Ana
authors.initials: A
authors.lastname: Gila
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gómez
authors.forename: Esther-José
authors.initials: EJ
authors.lastname: Pavón
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Muñoz
authors.forename: Angel
authors.initials: A
authors.lastname: Carazo
authors.forename: Paloma
authors.initials: P
authors.lastname: Sanz-Cameno
authors.forename: Ricardo
authors.initials: R
authors.lastname: Moreno-Otero
authors.forename: Moisés
authors.initials: M
authors.lastname: Diago
authors.forename: Josefa
authors.initials: J
authors.lastname: León
authors.forename: Angeles
authors.initials: A
authors.lastname: Ruiz-Extremera
authors.forename: Javier
authors.initials: J
authors.lastname: Salmerón
mesh_terms: D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D004359:Drug Therapy, Combination; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics*; D005802:Genes, MHC Class II / Q000235:genetics*; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012372:ROC Curve; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda