A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C |
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Authors: | Christian M Lange Stephanie Bibert Zoltan Kutalik Philippe Burgisser Andreas Cerny Jean-Francois Dufour Andreas Geier Tilman J Gerlach Markus H Heim Raffaele Malinverni Francesco Negro Stephan Regenass Klaus Badenhoop Jörg Bojunga Christoph Sarrazin Stefan Zeuzem Tobias Müller Thomas Berg Pierre-Yves Bochud Darius Moradpour;Swiss Hepatitis C Cohort Study Group |
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Institution: | Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. Christian.Lange@chuv.ch |
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Abstract: | BackgroundTo perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C.Methodology/Principal FindingsAssociations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p?=?0.02, OR?=?1.52, 95% CI?=?1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome.Conclusions/SignificanceOur study suggests a role of bioactive vitamin D (1,25OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome. |
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