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

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 1-alpha-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)D3<10ng/mL in 25% versus 12%, p<0.00001), which was in part reversible after HCV eradication. 25(OH)D3 deficiency correlated with SVR in HCV genotype 2 and 3 patients (63% and 83% SVR for patients with and without severe vitamin D deficiency, respectively, p<0.001). In addition, the CYPB27–1260 promoter polymorphism rs10877012 had substantial impact on 1–25-dihydroxyvitamin D serum levels and SVR rates in HCV genotype 1, 2 and 3 infected patients.

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.