Neopterin as a Marker of Response to Antiviral Therapy in Hepatitis C Virus Patients

Predicting the efficacy of antiviral treatment of hepatitis C virus (HCV) is of importance for both patient well-being and health care expense. The expression of interferon-stimulated genes (IFN-SGs) in the liver was suggested as a marker of response to anti-viral therapy. IFN-SGs encode the guanosine triphosphate cyclohydrolase 1 (GTPCH), a rate-limiting enzyme of pteridines biosynthesis. Neopterin, a stable byproduct of GTPCH-catalyzed reaction, is used as a marker of interferon-induced GTPCH activation. We hypothesized that assessment of neopterin concentrations might predict the response to antiviral therapy. Neopterin concentrations were evaluated in 260 HCV patients treated by pegylated interferon combined with ribavirin. Mean and median pretreatment neopterin concentrations were lower in patients with sustained virological response than in nonresponders. The rate of response was twofold higher among patients with pretreatment neopterin levels <16？nmol/L than in patients with neopterin levels ≥16？nmol/L, even after controlling for HCV genotype status. Our study suggests that the pretreatment level of neopterin might be used in routine clinical practice as rapid and cost-effective marker to predict the response to antiviral therapy in HCV patients. 1. Introduction Hepatitis C virus (HCV) is the most common blood-borne infection and a major cause of chronic liver disease, cirrhosis, and primary hepatocellular carcinoma and one of the leading indications for liver transplant [1]. The current standard therapy for chronic HCV (pegylated-interferon- (pegIFN-) combined with ribavirin) has limited efficacy (about 50%), is costly, and involves severe medical and psychiatric side effects. Recently introduced protease inhibitors, Telaprevir and Boceprevir, are effective in HCV1 and HCV2 while their antiviral activity is limited in HCV3 and HCV4 [2]. Therefore, search for biological markers to predict the response to antiviral treatment is of importance for both patient well-being and health care expense. HCV genotypes predict more favorite response among HCV1 and HCV4 (in comparison with HCV2- and HCV3- infected patients [1, 2]). The value of currently used assessment of allelic variants of the IL28B gene encoding IFNλ3 predicts antiviral response in HCV1 and HCV4 and is attenuated, but relevant also in HCV2 and HCV3, especially in patients not achieving rapid virological response [3]. Assessment of expression of interferon-stimulated genes (IFN-SGs) in the liver (but not in plasma) predicted antiviral response independently from IL28B polymorphism [4, 5].