Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy

J Hepatol. 2011 May;54(5):887-93. doi: 10.1016/j.jhep.2010.08.036. Epub 2011 Jan 20.


Background & aims: Vitamin D is an important immune modulator and preliminary data indicated an association between vitamin D deficiency and sustained virologic response (SVR) rates in hepatitis C virus (HCV) genotype 1 patients. We, therefore, performed a comprehensive analysis on the impact of vitamin D serum levels and of genetic polymorphisms with functional relevance within the vitamin D cascade on chronic hepatitis C and its treatment.

Methods: Vitamin D serum levels, genetic polymorphisms within the vitamin D receptor and 1α-hydroxylase were determined in a cohort of 468 HCV genotype 1, 2, and 3 infected patients who were treated with interferon-alfa based regimens.

Results: Chronic hepatitis C was associated with a high incidence of severe vitamin D deficiency compared to controls (25(OH)D(3)<10 ng/ml in 25% versus 12%, p<0.00001). 25(OH)D(3) deficiency correlated with SVR in HCV genotype 2 and 3 patients (50% and 81% SVR for patients with and without severe vitamin D deficiency, respectively, p<0.0001). In addition, the CYP27B1-1260 promoter polymorphism rs10877012 had substantial impact on 1,25-dihydroxyvitamin D serum levels (72, 61, and 60 pmol/ml for rs10877012 AA, AC, and CC, respectively, p=0.04) and on SVR rates in HCV genotype 1, 2, and 3 infected patients (77% and 65% versus 42% for rs10877012 AA, AC, and CC, respectively, p=0.02).

Conclusions: Chronic hepatitis C virus infection is associated with vitamin D deficiency. Reduced 25-hydroxyvitamin D levels and CYP27B1-1260 promoter polymorphism leading to reduced 1,25-dihydroxyvitamin D levels are associated with failure to achieve SVR in HCV genotype 1, 2, and 3 infected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics*
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / immunology
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Calcifediol / blood
  • Drug Resistance, Viral / immunology
  • Female
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / immunology
  • Hepatitis C, Chronic* / drug therapy
  • Hepatitis C, Chronic* / genetics
  • Hepatitis C, Chronic* / immunology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Polymorphism, Genetic / immunology
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / immunology
  • Receptors, Calcitriol / genetics
  • Retrospective Studies
  • Vitamin D Deficiency / genetics*
  • Vitamin D Deficiency / immunology
  • Young Adult


  • Antiviral Agents
  • Interferon-alpha
  • Receptors, Calcitriol
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcifediol