Source Liver Unit, Service of Gastroenterology, Hospital Clínico San Carlos & Department of Medicine, Complutense University. Madrid. Spain Department of Biochemistry & Molecular Biology, University of Extremadura, Badajoz. Spain Service of Clinical Epidemiology, Hospital Clínico San Carlos & School of Medicine, Complutense University, Madrid. Spain Laboratory of Molecular Genetics, Hospital de Terrassa, Terrassa (Barcelona). Spain. Department of Pharmacology, University of Extremadura, Badajoz, Spain Service of Clinical Microbiology, Hospital Clínico San Carlos & Department of Medicine, Complutense University, Madrid. Spain.

Background: Polymorphisms at the IL28B gene predict therapeutic response in chronic hepatitis C virus genotype 1 (CHC-1) infection.

Aims: 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: SNPs rs12979860 and rs8099917 were determined by TaqMan assays in 110 CHC-1 Caucasian patients treated with Peg-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 ), GGT (p = 0.022), alkaline phosphatase (p = 0.008), and cholesterol (p = 0.048). AUROC of the model including these variables is 0.841 (95 % 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), AST/ALT (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, rs8099917 genotype alone did not predict SVR (p = 0.185) but strongly predicted PNR (p = 0.003). The significance of haplotypes combining both SNPs as predictors of SVR and PNR was higher than those of each separate SNP.

Conclusions: rs12979860 SNP strongly predicts therapeutic response in CHC-1 patients and, associated with easy-to-obtain baseline criteria, is useful to select candidates for antiviral therapy. IL28B haplotypes may improve the clinical usefulness of individual SNPs.