Abstract
Purpose: To evaluate the role of pre-treatment vitamin D serum level and interleukin28B (IL28B) (rs 12979860) polymorphism in chronic hepatitis C (CHC) genotype 4a patients treated with pegylated interferon α2-A and ribavirin (peg IFN+RBV) as predictors of response.Methods: A retrospective study of clinical and pathological data and stored blood samples of 150 naïve chronic hepatitis C (CHC) genotype 4a patients, treated with pegylated interferon and ribavirin for 48 weeks. Follow-up to detect sustained virological response (SVR) was carried out. Based on SVR, two groups were studied; group 1 consisted of 75 responder patients to pegylated IFN + RBV therapy while group 2 comprised of 75 non-responder patients to standard hepatitis C virus (HCV) therapy. Vitamin D serum levels were assessed using Enzyme Linked Immunoassay (ELISA), quantitative reverse transcriptase- polymerase chain reaction (qRT-PCR for HCV RNA ), and IL28B gene polymorphism by Restriction Fragment Length Polymorphism Polymerase Cchain Reaction (RFLP-PCR).Results: Pretreatment vitamin D level was significantly higher in group 1 than in group 2 (p < 0.001). The sensitivity and specificity of vitamin D level for prediction of SVR at a cutoff value of 29.75 ng/ml were 100 and 96 %, respectively, with area under the curve (AUC) of 0.995 (p < 0.001). A significant difference was detected between baseline vitamin D level for early versus advanced fibrosis stage (p = 0.01) in group 1.Conclusion: Pretreatment vitamin D serum level (at a cutoff value of 29.75 ng/ml), IL28B gene polymorphism and quantitative HCV RNA are independent trait predictors of SVR.Keywords: Vitamin D, Interleukin 28B, Chronic hepatitis C, Sustained virological response (SVR), Antiviral, Genotyping
Highlights
The combination of pegylated interferon alpha-2a or alpha-2b plus ribavirin for 48 weeks is the recommended treatment for patients with hepatitis C virus (HCV) genotype 4, but many patients will not respond satisfactorily to this therapy [1]
Biological models for the prediction of sustained virological response (SVR) should include a variety of parameters besides IL28B genotyping, as this would offer better accuracy compared with IL28B typing alone [5]
This study aims to evaluate the role of Pretreatment vitamin D serum level and IL-28B polymorphism among other predictors of SVR and to study the relation between vitamin D serum level and hepatic fibrosis/activity scoring
Summary
The combination of pegylated interferon alpha-2a or alpha-2b plus ribavirin for 48 weeks is the recommended treatment for patients with HCV genotype 4, but many patients will not respond satisfactorily to this therapy [1]. It has side effects that prevent some patients from completing therapy [2]. For these reasons, identification of the determinants of responsiveness to treatment is a matter of high priority. Genome-wide association studies have recently revealed that single nucleotide polymorphisms (SNPs) within or adjacent to IL28B (19q13) that codes for interferon-λ3, predict spontaneous resolution of HCV. It was found that IL28B rs12979860 is strongly associated with the chance to clear HCV spontaneously in populations of African or European ancestry, with an approximately three times higher clearance rate in individuals with the rs12979860 genotype C/C versus C/T and T/T [3]. Biological models for the prediction of SVR should include a variety of parameters besides IL28B genotyping, as this would offer better accuracy compared with IL28B typing alone [5]
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