Therapy response in chronic hepatitis C patients is influenced by 25-OH Vitamin D serum levels and VDR (NR1I1) gene polymorphisms

K Baur; JC Mertens; J Schmitt; R Iwata; B Stieger; P Frei; B Seifert; B Müllhaupt; A Geier

doi:10.1055/s-0030-1269708

Zeitschrift für Gastroenterologie, Inhaltsverzeichnis

Therapy response in chronic hepatitis C patients is influenced by 25-OH Vitamin D serum levels and VDR (NR1I1) gene polymorphisms

K Baur ¹, JC Mertens ¹, J Schmitt ¹, R Iwata ¹, B Stieger ², P Frei ¹, B Seifert ³, B Müllhaupt ¹, A Geier ¹

¹Klinik für Gastroenterologie und Hepatologie, UniversitätsSpital Zürich, Schweiz, Zürich, Schweiz
²Institut für Klinische Pharmakologie und Toxikologie, UniversitätsSpital Zürich, Schweiz, Zürich, Schweiz
³Institut für Sozial- und Präventivmedizin, Abteilung Biostatistik, Universität Zürich, Zürich, Schweiz

Abstract

Aims: Chronic hepatitis C virus (HCV) infection is a major cause of end stage liver disease. Non-parenchymal liver cells involved in inflammation and fibrogenesis express functional vitamin D receptor (VDR). Vitamin D is a known immunomodulator. We investigated effects of vitamin D serum levels and common polymorphisms (SNP) in the VDR (NR1I1) gene on hepatic inflammation & therapy response in chronic HCV-patients. Methods: 156 patients were included for VDR genotyping (Cdx2 rs11568820, bat genptype: Bsm rs1544410, Apa rs 7975232 and Taq rs 731236). Serum vitamin D levels were measured in patients with early fibrosis (F0–1) not affecting vitamin D homeostasis. Exclusion criteria were HBV or HIV coinfection, alcohol >40g/day and morbid obesity. Statistical associations with Metavir inflammation score (A) and sustained virological response (SVR) to PEG-interferon/ribavirin standard therapy were calculated. Results: Significant correlation with HCV-therapy failure was seen for the ApaI (CC) and TaqI (TT) genotypes (non-SVR vs. SVR; ApaI P=0.037; CC vs. CA/AA P=0.013; OR 2.66; TaqI P=0.018; CC vs. CA/AA P=0.002; OR 6.05). Also the most frequent bAt-haplotype (Bsm C_Apa C_Taq_A) was associated with non-SVR vs. SVR (P=0.045 vs. any other haplotype; P=0.028 vs. all other haplotypes combined; OR 1.69). 50.3% of bAt-haplotype patients showed non-SVR. Age (p=0.029, OR 1.80), HCV genotype (p=0.0001, OR 5.37) and the bAt haplotype (p=0.024, OR 1.78) were confirmed as significant, independent predictors of non-SVR in multivariate logistic regression analysis. Vitamin D levels were clearly association with non-SVR (18.1 vs. 27.7 ug/L for SVR; p=0.05). No significant association was observed for any VDR genotype or haplotype to Metavir inflammatory activity. Conclusions: Serum vitamin D levels and common VDR SNPs are associated with therapy response in chronic HCV-patients. Substitution of vitamin D during antiviral therapy may be an attractive approach.

Hepatitis C - NR1I1 - Polymorphisms - Therapy response - VDR - Vitamin D