title: Variations at multiple genes improve interleukin 28B genotype predictive capacity for response to therapy against hepatitis C infection.
abstract: OBJECTIVE
  To identify genetic factors that predict sustained virological response (SVR) to pegylated interferon (Peg-IFN)/ribavirin (RBV) in HIV/hepatitis C virus (HCV) genotype 1 or 4-coinfected patients and that enhance the predictive capacity of IL28B genotype in this population.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  Five tertiary care centers in Spain.
  
  
  METHODS
  Two hundred and five HIV/HCV genotype 1 or 4-coinfected patients who received a complete course of Peg-IFN/RBV for 48 weeks.
  
  
  METHODS
  All individuals were genotyped for 144 single-nucleotide polymorphisms (SNPs).
  
  
  RESULTS
  One hundred and sixty-two (79%) patients bore HCV genotype 1. Overall SVR was achieved by 73 (36%) individuals. SNPs at the following genes were associated with SVR: IL28B, low-density lipoprotein receptor (LDLR), transforming growth factor β (TGF-β), aquaporine 2 (AQP-2), very-low-density lipoprotein receptor, Sp110 nuclear body protein, interferon alpha/beta receptor 1, 2'-5'-oligoadenylate synthase 1 and apolipoprotein B. There was a strong synergy between SNPs at IL28B, TGF-β and AQP-2 genes: the number of patients reaching SVR with all three favorable genotypes versus unfavorable genotypes were 22 (78.6%) versus 1 (7.1%) (P = 2.1 × 10). HCV baseline viral load, IL28B, TGF-β, AQP-2 and LDLR haplotypes were independently associated with SVR.
  
  
  CONCLUSIONS
  A number of genetic factors modify the predictive capacity of IL28B genotype. These can be used to identify HCV genotype 1 or 4-infected patients with a very high or a very low probability to respond to bitherapy with Peg-IFN/RBV. Predictive models based on these factors could be helpful to tailor direct acting antiviral-based therapy.
authors.affiliation: aUnit of Infectious Diseases and Microbiology, Hospital Universitario de Valme bInstituto de Biomedicina de Sevilla (IBiS), Seville cImmunogenetics Unit, Faculty of Sciences, Universidad de Jaén, Jaen dUnit of Infectious Diseases, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Cordoba eDepartment of Infectious Diseases, Hospital Carlos III, Madrid fUnit of Infectious Diseases, Hospital Juan Ramón Jiménez. Huelva, Spain.
authors.forename: Karin
authors.initials: K
authors.lastname: Neukam
authors.forename: Antonio
authors.initials: A
authors.lastname: Caruz
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero-Juárez
authors.forename: Pablo
authors.initials: P
authors.lastname: Barreiro
authors.forename: Dolores
authors.initials: D
authors.lastname: Merino
authors.forename: Luis M
authors.initials: LM
authors.lastname: Real
authors.forename: Rocío
authors.initials: R
authors.lastname: Herrero
authors.forename: Angela
authors.initials: A
authors.lastname: Camacho
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.forename: Federico A
authors.initials: FA
authors.lastname: Di Lello
authors.forename: Juan
authors.initials: J
authors.lastname: Macías
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D007378:Interleukins / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D013030:Spain; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda