Z Gastroenterol 2010; 48 - P461
DOI: 10.1055/s-0030-1263901

Therapy response in chronic hepatitis C patients is affected by common Vitamin D Receptor (NR 1I1) polymorphisms

K Baur 1, JC Mertens 1, J Schmitt 1, R Iwata 1, B Stieger 2, 3, P Frei 1, J Braun 4, B Müllhaupt 1, 3 A Geier 1, 3, 5, Swiss Hepatitis C Cohort Study Group (SCCS)
  • 1University Hospital Zürich, Clinic for Gastroenterology & Hepatology, Zürich, Switzerland
  • 2University Hospital Zürich, Department of Clinical Pharmacology, Zürich, Switzerland
  • 3University Hospital Zürich, Swiss HPB-Center, Zürich, Switzerland
  • 4University of Zürich, Institute for Biostatistics, Zürich, Switzerland
  • 5University of Zürich, Center for Integrative Human Physiology (ZIHP), Zürich, Switzerland

Background and aims: Chronic hepatitis C virus (HCV) infection represents a leading cause of end stage liver disease worldwide. Non-parenchymal hepatic cells as mediators of inflammation and fibrogenesis such as sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells do express VDR mRNA and functionally active VDR protein. Given the established role of vitamin D as an immunomodulator it is straightforward to investigate a potential effect of common polymorphisms in the VDR (NR1I1) gene on hepatic inflammation and therapy response.

Methods: Overall, 166 patients with available blood samples and liver biopsies were included for TaqMan VDR genotyping (Cdx2 rs11568820, bat haplotype consisting of Bsm rs1544410, Apa rs 7975232 and Taq rs 731236). 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: The ApaI (CC) and TaqI (TT) genotypes showed a significant correlation with HCV-therapy failure (non-SVR vs. SVR; ApaI P=0.037; CC vs. CA/AA P=0.012; OR 2.66; TaqI P=0.018; CC vs. CA/AA P=0.002; OR 6.05). Likewise, the most frequent bAt-haplotype (Bsm CC_Apa CC_Taq TT) was associated with non-SVR vs. SVR (P=0.005 vs. any particular other haplotype; P=0.009 vs. all other haplotypes combined; OR 2.66). Of note, 62.2% of bAt-haplotype patients are non-responders. In addition, also Cdx2 TT is also associated with non-SVR (P=0.016 for TT vs. CT/CC) but the small number of TT-nonresponders (n=5) limits definite conclusions. Logistic regression analysis between the observed haplotypes confirmed ApaI CC and TaqI TT as two significant (for ApaI CC P=0.043; for TaqI TT 0.019) and frequently coexisting polymorphisms with respect to all occurring haplotype combinations. No significant association was observed for any VDR genotype or haplotype to Metavir inflammatory activity.

Conclusions: VDR polymorphisms are significantly associated with the therapeutic response to interferon/ribavirin in chronic HCV-patients. Whether substitution of vitamin D during antiviral therapy may be an attractive approach remains subject of future clinical studies.