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

• DOI: 10.1016/j.jhep.2010.08.036
• Publication Date: 2010-10-23T08:18:58Z
• Authors: Christian Markus ...; Jörg Bojunga; Elizabeth Ramos-L...; Michael von Wagner; Angela Hassler; Johannes Vermehren; Eva Herrmann; Klaus Badenhoop; Stefan Zeuzem; Christoph Sarrazin
• Keywords: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Adult; Male; 0301 basic medicine; Polymorphism, Genetic; Genotype; Interferon-alpha; Hepacivirus; Hepatitis C, Chronic; Middle Aged; Vitamin D Deficiency; Antiviral Agents; 3. Good health; Young Adult; 03 medical and health sciences; Drug Resistance, Viral; Humans; Receptors, Calcitriol; Female; Promoter Regions, Genetic; Aged; Calcifediol; Retrospective Studies

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.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.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).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.