Homozygosity for HLA Group 2 Alleles Predicts Treatment Failure with Interferon-[alpha] and Ribavirin in Chronic Hepatitis C Virus Genotype 1 Infection

• Published in: Journal of interferon & cytokine research Vol. 35; no. 2; p. 126
• Main Authors: Collison, Meadhbh, Chin, Jun Liong, Abu Shanab, Ahmed, Mac Nicholas, Ross, Segurado, Ricardo, Coughlan, Suzie, Connell, Jeff, Carr, Michael J, Merriman, Raphael B, McCormick, P Aiden, Hall, William W
• Format: Journal Article
• Language: English
• Published: New Rochelle Mary Ann Liebert, Inc 01.02.2015
• ISSN: 1079-9907; 1557-7465
• DOI: 10.1089/jir.2014.0088

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[sup]-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[sup]-4) and dominant models (P=3.83×10[sup]-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).