Vitamin D levels vary during antiviral treatment but are unable to predict treatment outcome in HCV genotype 1 infected patients

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Abstract

Background: Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed. Methods: In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-α and ribavirin for 24-72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome. Results: Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) % of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002-1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975-0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000-1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073-2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271-4.695, P = 0.007) constituted the strongest predictors of treatment response. Conclusions: While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients. © 2014 Grammatikos et al.

Figures

  • Table 1. Patient demographic, biochemical and genetic characteristics.
  • Figure 1. VitD concentrations vary dependent on the month of sample obtainment (1A), whereas fluctuations between baseline-VitD and TW24-VitD-values (DVitd) are observed as well (1B). doi:10.1371/journal.pone.0087974.g001
  • Table 2. Uni- and multivariate analysis of predictors of SVR to antiviral therapy.
  • Table 3. SNP’s within VitD regulating enzymes in association with baseline VitD values and VitD variations (DVitd) upon antiviral therapy.
  • Figure 2. High cholesterol- and low gGT- levels associate with achievement of SVR and ETR.
  • Figure 3. Variations of IP10-levels in patients with and without SVR at baseline, week 1 and 4 upon treatment initiation.
  • Figure 4. The DHCR7-TT-genotype of the rs12785878 SNP shows a significant association to stage of fibrosis. doi:10.1371/journal.pone.0087974.g004

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Grammatikos, G., Lange, C., Susser, S., Schwendy, S., Dikopoulos, N., Buggisch, P., … Sarrazin, C. (2014). Vitamin D levels vary during antiviral treatment but are unable to predict treatment outcome in HCV genotype 1 infected patients. PLoS ONE, 9(2). https://doi.org/10.1371/journal.pone.0087974

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