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

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 Taq Man 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 < 400.000 IU/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 ≥ 400.000 IU/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.