Reply to “Vitamin D deficiency and HCV chronic infection: What comes first?”
Authors: Christian M. Lange, Jörg Bojunga, Klaus Badenhoop, Stefan Zeuzem, Christoph Sarrazin
Journal: Journal of Hepatology (2011)

Vitamin D deficiency and HCV chronic infection: What comes first?Journal of HepatologyVol. 55Issue 4PreviewDear Sir, we read with great interest the paper published by Lange et al. [1] reporting that serum vitamin D deficiency and the CYP27B1-1260 promoter polymorphism are more prevalent in patients with chronic hepatitis C compared to controls, and that they are associated with a lower response rate to interferon-alfa based therapy. Comparing patients with chronic hepatitis C to a large control group, the authors found a strong association between the presence of chronic hepatitis C and severe vitamin D (25-OH D3) deficiency (serum levels <10 ng/ml in 25% of the patients vs. Full-Text PDF Open Access We thank Dr. Bitetto et al. for their interest in our study recently published in the Journal of Hepatology [[1]Lange C.M. Bojunga J. Ramos-Lopez E. von Wagner M. Hassler A. Vermehren J. et al.Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy.J Hepatol. 2010; 54: 887-893Abstract Full Text Full Text PDF Scopus (213) Google Scholar]. In this study, we reported a high prevalence of severe vitamin D deficiency in patients with chronic hepatitis C, even in the absence of significant liver fibrosis. We found that vitamin D deficiency was associated with failure to achieve a sustained virologic response (SVR) to therapy of chronic hepatitis C with pegylated interferon-alfa and ribavirin. Bitetto et al. have now accentuated the important question, whether vitamin D deficiency is caused by hepatitis C virus (HCV) infection, or whether vitamin D deficiency may confer an enhanced susceptibility to chronic HCV infection. We believe that this question cannot be finally answered at the moment. In our study, we reported a slight increase of 25-hydroxyvitamin D serum levels from baseline to week 24 after completion of antiviral therapy in those patients who achieved a SVR. As highlighted by Bitetto et al. and others [2Bitetto D. Fattovich G. Fabris C. Ceriani E. Falleti E. Fornasiere E. et al.Complementary role of vitamin D deficiency and the IL-28B rs12979860 C/T polymorphism in predicting antiviral response in chronic hepatitis C.Hepatology. 2011; 53: 1118-1126Crossref PubMed Scopus (121) Google Scholar, 3Wang T.J. Zhang F. Richards J.B. Kestenbaum B. van Meurs J.B. Berry D. et al.Common genetic determinants of vitamin D insufficiency: a genome-wide association study.Lancet. 2010; 376: 180-188Abstract Full Text Full Text PDF PubMed Scopus (1309) Google Scholar], we have made an attempt to stratify the patients included in this sub-analysis according to the season in which serum samples for vitamin D measurement were taken. In detail, 50% of patients started therapy in winter/spring and SVR was ascertained in summer/autumn, which was vice versa in the remaining 50% of patients. Meanwhile, we have also re-analyzed our complete cohort according to the season when baseline serum samples for vitamin D detection were taken. Although we observed slightly lower baseline 25-hydroxyvitamin D serum levels in patients who started therapy in winter/spring compared to summer/autumn (mean 16.6 and 18.7 ng/ml, p= 0.054), severe vitamin D deficiency (<10 ng/ml) was associated with chronic HCV infection during all seasons (26% vs. 19% in winter/spring vs. summer/autumn, respectively, compared to 20% vs. 6% in winter/spring vs. summer/autumn samples in our non-HCV infected control group). In addition, season had no significant influence on SVR rates. Nevertheless, we fully agree with Bitetto et al. that our observations do not prove that HCV infection itself can cause vitamin D deficiency. In addition to a residual season influence, factors such as changes in life-style or eating habits may contribute to the increase of vitamin D serum levels after successful HCV eradication. To resolve the “what comes first” question results of basic research on a potential interplay between HCV infection and vitamin D metabolism, as well as additional clinical data from large and well defined patient cohorts are required. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.