Combined effects of different IL 28 B gene variants on the outcome of dual combination therapy in chronic HCV type 1 infection

In patients with chronic hepatitis C virus infection (HCV) several variants of the IL28B gene have been shown to correlate significantly with a sustained virologic response (SVR). Recent evidence shows that determination of one single IL28B polymorphism rs12979860 is sufficient for predicting treatment outcome. We examined whether the combined determination of the IL28B single nucleotide polymorphisms (SNP) rs12979860, rs8099917, rs12980275 and rs8103142 might improve prediction of SVR in patients with HCV. In the study cohort, 54% of 942 patients with chronic HCV type 1 infection had SVR. The IL28B SNPs rs12979860CC and rs8099917TT correlated significantly with SVR (68% and 62%). The SNPs rs12980275 and rs8103142 were in strong linkage disequilibrium with rs12979860 and were not included in further analysis. In homozygous carriers of the rs12979860 responder allele C, additional genotyping of the rs8099917 SNP had no impact on response prediction, while in carriers of the rs12979860 non-responder allele the rs8099917 SNP improved the response prediction. In heterozygous carriers of the rs12979860 non-responder T allele SVR rates were 55% in the presence of the rs8099917TT genotype and 40% in patients carrying the rs8099917 TG or GG genotype. Analysis of an independent confirmation cohort of 377 HCV type 1-infected patients verified the significant difference in SVR rates between the combined genotypes rs12979860CT/rs8099917TT and rs12979860CT/rs8099917TG (38% vs. 21%, p=0.018). Conclusion: Treatment outcome prediction could not be improved in homozygous carriers of the IL28B rs12979860 C responder allele by the additional determination of the rs8099917 SNPs. There is evidence that a significant proportion of heterozygous carriers of the rs12979860 T non-responder allele can profit with respect to SVR prediction by further determination of the rs8099917 SNPs. Page 5 of 38 Hepatology Hepatology