Genome-wide association of IL-28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C in a Tunisian population.

ABSTRACT

BACKGROUND:   A polymorphism upstream of interleukin (IL)-28B was recently identified to be associated with a 2-fold difference in sustained virologic response (SVR) to pegylated interferon-alpha and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C (CHC) virus genotype 1 (HCV-1) infection. AIM: We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment virologic response and SVR. METHODS: We perform a prospective study in gastroenterology unitof tunis'military hospital in collaboration with immunology unit, military center of blood transfusion and laboratory of biochemistry of childrens' hospital of Tunis. HCV patients were genotyped as CC, CT or TT at the polymorphic site rs12979860 and TT, TG or GG at the polymorphic site rs8099917. Viral kinetics and rates of rapid virologic response (RVR, week 4) and SVR were compared by IL-28B type in a tunisian population. RESULTS: 154 patients including 80 healthy blood donors(sexratio 1, mean age 40.35 ±10.15 years) and 74 patients treated for CHC (39 men and 35 women; mean age = 51.7± 9.4 years) were enrolled. 35.6% of patients were genotyped as CC at the polymorphic site rs12979860 and 69.1% as TT at the polymorphic site rs8099917. The CC IL-28B type at rs12979860 was associated with a greater likelihood of SVR (77% vs 31.9%; p<0.001; OR 7.11 [2.37-21.35]) compared with CT and TT. The CC IL-28B type at rs12979860 wasn't associated with improved of rapid virologic response (RVR). In a multivariate logistic regression model, the rs12979860 CC genotype predicted SVR (p<0.001; OR 7.11 IC95% [2.37-21.35]). The TT IL-28B type at rs 8099917 wasn't associated with improved RVR and SVR compared with TG and GG. CONCLUSION: In treatment-naive HCV patients treated with pegylated interferon and ribavirin, a polymorphism upstream CC at the site rs12979860 of IL-28B is associated with increased sustained virologic response and effectively predicts treatment outcome.