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

PLoS One. 2012;7(7):e40159. doi: 10.1371/journal.pone.0040159. Epub 2012 Jul 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Adult
  • Aged
  • Calcifediol / blood
  • Demography
  • Female
  • Gene Frequency / genetics
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Reproducibility of Results
  • Ribavirin / therapeutic use
  • Seasons
  • Treatment Outcome
  • Vitamin D / blood
  • Vitamin D / metabolism*
  • Young Adult


  • IFNL3 protein, human
  • Interferon-alpha
  • Interleukins
  • Vitamin D
  • Ribavirin
  • Interferons
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcifediol