title: Homozygosity for HLA group 2 alleles predicts treatment failure with interferon-α and ribavirin in chronic hepatitis C virus genotype 1 infection.
abstract: Host genetic factors influence treatment responses to antiviral therapy in chronic hepatitis C virus (HCV) infection. We retrospectively investigated associations between host genetic markers and treatment-induced virologic responses to dual therapy with interferon-α and ribavirin in chronically infected HCV genotype 1 (g1)- and genotype 3 (g3)-infected individuals. A total of 171 patients (89 HCV g1 and 82 HCV g3 infected) were investigated for genetic markers influencing treatment-induced sustained virologic response (SVR). Overall, SVR was observed for 46/89 (52%) HCV g1- and 57/82 (70%) HCV g3-infected patients. Of the 4 interleukin 28B (IL28B) single-nucleotide polymorphisms (SNPs), rs12979860 was the host genetic marker most significantly associated with failure to achieve an SVR in HCV g1-infected individuals [P=3.83×10(-4); odds ratio (OR)=5.61; confidence interval (CI)=2.07-15.18] and gave a positive predictive value for treatment failure of 81.3% for minor homozygotes (TT). Using additive (P=3.54×10(-4)) and dominant models (P=3.83×10(-4)), a dosage effect of the T allele was observed, with the dominance term not significant for this SNP. Logistic regression showed an association between HLA-C1/C1 and rapid virologic response in HCV g1 infections with an OR relative to the heterozygote of 10.0 (95% CI: 1.6-62.5, P=0.014). HLA-C2 homozygosity was a significant predictor of nonresponse to treatment in HCV g1-infected individuals (P=0.023).
authors.affiliation: 1 National Virus Reference Laboratory, University College Dublin , Dublin, Ireland .
authors.forename: Meadhbh
authors.initials: M
authors.lastname: Collison
authors.forename: Jun Liong
authors.initials: JL
authors.lastname: Chin
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abu Shanab
authors.forename: Ross
authors.initials: R
authors.lastname: Mac Nicholas
authors.forename: Ricardo
authors.initials: R
authors.lastname: Segurado
authors.forename: Suzie
authors.initials: S
authors.lastname: Coughlan
authors.forename: Jeff
authors.initials: J
authors.lastname: Connell
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Carr
authors.forename: Raphael B
authors.initials: RB
authors.lastname: Merriman
authors.forename: P Aiden
authors.initials: PA
authors.lastname: McCormick
authors.forename: William W
authors.initials: WW
authors.lastname: Hall
mesh_terms: D000483:Alleles; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D006720:Homozygote; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012254:Ribavirin / Q000008:administration & dosage*
chemical_list: D000998:Antiviral Agents; D015236:HLA-C Antigens; D016898:Interferon-alpha; D012254:Ribavirin