PLoS ONE (Jan 2012)

A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C.

  • 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

DOI
https://doi.org/10.1371/journal.pone.0040159
Journal volume & issue
Vol. 7, no. 7
p. e40159

Abstract

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BACKGROUND:To 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 FINDINGS:Associations 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 D(3) (25[OH]D(3)) 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 (25[OH]D(3)<20 ng/mL) during all seasons, but 25(OH)D(3) serum levels were not associated with treatment outcome. CONCLUSIONS/SIGNIFICANCE:Our study suggests a role of bioactive vitamin D (1,25[OH](2)D(3), calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D(3) is not a suitable predictor of treatment outcome.