Complementary role of vitamin D deficiency and the interleukin-28B rs12979860 C/T polymorphism in predicting antiviral response in chronic hepatitis C

Authors

  • Davide Bitetto,

    1. Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
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  • Giovanna Fattovich,

    1. Gastroenterology Clinic, Department of Medicine, Azienda Ospedaliero-Universitaria, University of Verona, Verona, Italy
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  • Carlo Fabris,

    1. Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
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  • Elisa Ceriani,

    1. Department ofClinical and Experimental Medicine, University of Piemonte Orientale, Novara, Italy
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  • Edmondo Falleti,

    1. Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
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  • Ezio Fornasiere,

    1. Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
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  • Michela Pasino,

    1. Gastroenterology Clinic, Department of Medicine, Azienda Ospedaliero-Universitaria, University of Verona, Verona, Italy
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  • Donatella Ieluzzi,

    1. Gastroenterology Clinic, Department of Medicine, Azienda Ospedaliero-Universitaria, University of Verona, Verona, Italy
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  • Annarosa Cussigh,

    1. Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
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  • Sara Cmet,

    1. Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
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  • Mario Pirisi,

    1. Department ofClinical and Experimental Medicine, University of Piemonte Orientale, Novara, Italy
    2. Research Centre for Autoimmune Diseases, Novara, Italy
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  • Pierluigi Toniutto

    Corresponding author
    1. Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
    • Department of Medicine and Pathology Clinical and Experimental, Internal Medicine, Medical Liver Transplantation Unit, University of Udine, Udine, Italy
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    • fax: (39)-559490


  • Potential conflict of interest: Nothing to report.

  • Supported in part by grants from the Ricerca Sanitaria Finalizzata Program, Regione Piemonte, Italy (to M. P.).

Abstract

The widely accepted interleukin-28B (IL-28B) rs12979860 C/T polymorphism and the more recently proposed vitamin D serum concentration are two novel predictors of the response to antiviral treatment in chronic hepatitis C virus (HCV) infection. This study aimed to verify whether the IL-28B rs12979860 C/T polymorphism and pretreatment serum vitamin D levels have independent or complementary roles in predicting the rates of sustained viral response (SVR). The present study included 211 consecutive, treatment-naïve chronic HCV patients who had their pretreatment serum 25-OH vitamin D level and IL-28B rs12979860 C/T genotype determined. Overall, SVR was achieved by 134/211 (63.5%) patients and by 47/110 (42.7%) patients infected with difficult-to-treat HCV genotypes. On multivariate analysis, SVR was predicted by the HCV genotype, the IL-28B rs12979860 C/T polymorphism, and gamma-glutamyl transpeptidase, HCV RNA, cholesterol, and 25-OH vitamin D serum levels, with an area under the receiver operating characteristic (ROC) curve of 0.827. When difficult-to-treat HCV genotypes were analyzed separately, the SVR was predicted by the IL-28B rs12979860 C/T polymorphism, viral load, and serum vitamin D level, with an area under the ROC curve of 0.836. Moreover, by categorizing these latter patients into four groups—C/C homozygotes with vitamin D levels >20 ng/mL (group A) or ≤20 ng/mL (group B) and C/T heterozygotes or T/T homozygotes with vitamin D levels >20 ng/mL (group C) or ≤20 ng/mL (group D)—a significant linear trend was observed, with SVR rates in the following descending order: group A, 18/21 (85.7%); group B, 6/11 (54.5%); group C, 14/38 (36.8%); and group D, 9/40 (22.5%) (P < 0.0001). Conclusion: Vitamin D serum levels are complementary to the IL-28B rs12979860 C/T polymorphism in enhancing the correct prediction of the SVR in treatment-naïve chronic hepatitis C. (HEPATOLOGY 2011;)

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