Vitamin D Levels Vary during Antiviral Treatment but Are Unable to Predict Treatment Outcome in HCV Genotype 1 Infected Patients

Abstract

BackgroundDifferent 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.MethodsIn 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.ResultsFluctuations 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.ConclusionsWhile 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.

Vitamin D level and sustained virologic response to interferon-based antiviral therapy in chronic hepatitis C: A systematic review and meta-analysis

“…Therefore, 11 studies, comprised of 7 published articles [5][6][7][8][9][10][11] and 4 conference abstracts [20][21][22][23], involving 2605 patients with chronic HCV infection, were included in the meta-analysis (Fig. 1).…”

“…While some studies found an independent association between a higher baseline 25(OH)D level and SVR in HCV genotype 1/4/5 infection [5][6][7] and genotype 2/3 infection [8], others failed to find any relationship between baseline vitamin D level and treatment response [9][10][11]. These discordant results have led to uncertainty whether the baseline vitamin D level has any influence on SVR to PEG-IFN plus RBV antiviral therapy in chronic HCV infection.…”

Vitamin D‐related gene polymorphisms do not influence the outcome and serum vitamin D level in pegylated interferon/ribavirin therapy combined with protease inhibitor for patients with genotype 1b chronic hepatitis C

“…Thus, in the present study, rs7944926 was analyzed. Previous studies have shown that genotypes with the G allele for DHCR7 (rs7944926), G allele for CYP2R1 (rs10741657), G allele for GC (rs2282679), and T allele for CYP27B1 (rs10877012) are risk factors for low serum 25(OH) D 3 levels [Lange et al, 2011[Lange et al, , 2012[Lange et al, , 2013Grammatikos et al, 2014]. A non-carrier of the T allele for VDR gene (rs2228570) is also considered a risk factor for low serum 25(OH) D 3 levels [Garcia-Martin et al, 2013].…”

“…Several vitamin D-related gene polymorphisms were reported to contribute to SVR [Lange et al, 2011[Lange et al, , 2012Baur et al, 2012;Falleti et al, 2012;Garcia-Martin et al, 2013;Grammatikos et al, 2014]. We analyzed whether these polymorphisms could influence serum 25(OH) D 3 levels.…”

“…In recent years, it has been reported that serum vitamin D level and several vitamin D-related gene polymorphisms also contribute to the achieving of SVR [Petta et al, 2010;Bitetto et al, 2011]. Specifically, polymorphisms in vitamin D binding protein (GC) [Falleti et al, 2012], 7-Dehydrocholesterol reductase (DHCR7) [Grammatikos et al, 2014], cytochrome p450 27B1 (CYP27B1) [Lange et al, 2011[Lange et al, , 2012, and vitamin D receptor (VDR) gene [Baur et al, 2012;Garcia-Martin et al, 2013] are known to have an important association with SVR in PR therapy.…”