IL28B polymorphisms determine early viral kinetics and treatment outcome in patients receiving peginterferon/ribavirin for chronic hepatitis C genotype 1

Single nucleotide polymorphisms (SNPs) upstream of IL28B predict the outcome of treatment in chronic hepatitis C virus (HCV) infection, but their impact on viral kinetics and relation to other predictors are not well known. Here, two SNPs, rs12979860 and rs8099917, were analysed and related to early viral kinetics during treatment in 110 patients with HCV genotype 1 infection. The reduction of HCV RNA after 7 days of therapy was more pronounced (P < 0.0001) in patients with CCrs12979860 or TTrs8099917 than in patients carrying TTrs12979860 or GG(rs8099917), respectively. The two SNPs were in linkage disequilibrium (d' = 1, r(2) = 0.44), but CCrs12979860 was less common (43% vs 71%) than TTrs8099917. Patients carrying both CCrs12979860 and TTrs8099917 genotypes achieved lower levels of HCV RNA at week 4 than those with CT or TT at rs12979860 and TTrs8099917 (P = 0.0004). The viral elimination was significantly influenced by rs12979860 independently of baseline viral load, age or fibrosis. This translated into high rates of sustained viral response (SVR) among patients carrying CCrs12979860 despite the presence of high viral load at baseline (SVR 74%), high age (SVR 79%) or severe liver fibrosis (SVR 83%). We conclude that the IL28B variability influences the antiviral efficiency of interferon/ribavirin therapy and has a strong impact on SVR, independently of traditional response predictors. A combined assessment of these SNPs in conjunction with other response predictors may better predict outcome in difficult-to-treat patients.