Predicting response to therapy in chronic hepatitis C: An approach combining interleukin-28B gene polymorphisms and clinical data

Abstract

Background and Aim: 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 <400.000IU/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 ≥400.000IU/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. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.