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. 2010 Dec 8. [Epub ahead of print]

Lange CM, Bojunga J, Ramos-Lopez E, Wagner MV, Hassler A, Vermehren J, Herrmann E, Badenhoop K, Zeuzem S, Sarrazin C.

Klinikum der J. W. Goethe-Universität Frankfurt am Main, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.

Abstract

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 CYPB27-1260 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 CYPB27-1260 promotor polymorphism leading to reduced 1,25-dihydroxyvitamin D levels are associated with failure to achieve SVR in HCV genotype 1, 2, 3 infected patients.

Copyright © 2010. Published by Elsevier B.V.

PMID: 21145801 [PubMed - as supplied by publisher]

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