Complementary Role of Neopterin and the IL-28B Polymorphism in Predicting Antiviral Response in Genotype 4 Chronic Hepatitis C Virus Patients

Abstract

Background and Aims : Neopterin, a water-soluble stable byproduct of the first reaction of the GTPCH induced inhibition of the pteridines biosynthesis, is used as a marker of interferon-induced GTPCH activation suggesting its use as a marker of response to anti-viral therapy. IL28B polymorphism is an established predictor of response to pegylated interferon-Ribavirin therapy. The aim of the study is to verify the role of pretreatment serum neopterin level with or without IL28B polymorphism in predicting the rate of SVR in genotype 4 chronic hepatitis C (CHC) patients. Patients and Methods : This prospective cohort study included 102 treatment naA¯ve genotype 4 CHC patients treated with pegylated interferon/ribavirin therapy. Pretreatment IL28B rs12979860 C/T polymorphism and serum neopterin level were determined. Results : SVR was achieved in 65/102 (63.7%) patients. Regarding IL28B genotypes, 20% of CC genotype (4/20), 39% of TC genotype (20/51), and 42% of TT genotype (13/31) were non responders. A cutoff level of serum neopterin >18.68 nmol/L (AUC=0.695) predicted 29/37 (78.4%) non-responders. The favorable IL28B genotype (CC) was good predictor of response irrespective of serum neopterin level. Adding serum neopterin with cutoff > 18.68 nmol/L to the unfavorable IL28B genotypes (CT/TT) improves the prediction rate of non-responders [33/82 (40.2%) versus 25/33 (75.8%)], with 75.8% sensitivity, 63.2% specificity, 58% PPV and 79.5% NPV (P=0.001). Conclusion : High serum neopterin level could improve the predictive value for non-responders in CHC patients with unfavorable IL28B genotypes (CT/TT) suggesting their allocation to the more expensive IFN-free regimens.