Reply to: “Evidence supporting a beneficial role of vitamin D in chronic hepatitis C”
Authors: Matthew T. Kitson, Christoph Sarrazin, Pierluigi Toniutto, Stuart Keith Roberts
Journal: Journal of Hepatology (2015)

Vitamin D level and sustained virologic response to interferon-based antiviral therapy in chronic hepatitis C: A systematic review and meta-analysisJournal of HepatologyVol. 61Issue 6PreviewThe baseline 25-hydroxyvitamin D (25[OH]D) level has recently been reported to be an independent predictor of sustained virologic response (SVR) to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV) for chronic hepatitis C virus (HCV) infection. However, studies have yielded inconsistent results. Thus, we conducted a systematic review and meta-analysis to clarify any association between baseline 25(OH)D level and SVR in HCV therapy. Full-Text PDF Evidence supporting a beneficial role of vitamin D in chronic hepatitis CJournal of HepatologyVol. 63Issue 2PreviewWe read with interest the recent meta-analysis by Kitson et al. [1]. The authors show that baseline vitamin D level is not associated with sustained virologic response (SVR) to pegylated interferon (PegIFN) plus ribavirin therapy in patients with chronic hepatitis C (CHC). Based on this finding, they question [1] the non-skeletal benefits of vitamin D supplements, an essential determinant in regulating bone metabolism in chronic liver disease [2], on CHC. However, as vitamin D deficiency has been identified as a main risk factor for CHC development, we believe that the non-skeletal benefits of this kind of vitamin on patients with CHC cannot be negligible and the conclusions of this meta-analysis [1] needs to be further discussed and researched. Full-Text PDF Open Access We thank Pang et al. for their interest in our recently published systematic review and meta-analysis involving 2605 patients which found no association between baseline 25-hydroxyvitamin D level and sustained virologic response (SVR) to interferon-based antiviral therapy in chronic hepatitis C infection [[1]Kitson M.T. Sarrazin C. Toniutto P. Eslick G.D. Roberts S.K. Vitamin D level and sustained virologic response to interferon-based antiviral therapy in chronic hepatitis C: a systematic review and meta-analysis.J Hepatol. 2014; 61: 1247-1252Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar]. They are correct to highlight the influence of ethnicity on both vitamin D status and genetic polymorphisms in key proteins involved in vitamin D synthesis. The studies included in our meta-analysis contained only a small number of participants of Asian [[2]Kitson M.T. Dore G.J. George J. Button P. McCaughan G.W. Crawford D.H. et al.Vitamin D status does not predict sustained virologic response or fibrosis stage in chronic hepatitis C genotype 1 infection.J Hepatol. 2013; 58: 467-472Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar] or African-American [[3]Weintraub S.J. Fleckenstein J.F. Marion T.N. Madey M.A. Mahmoudi T.M. Schechtman K.B. Vitamin D and the racial difference in the genotype 1 chronic hepatitis C treatment response.Am J Clin Nutr. 2012; 96: 1025-1031Crossref PubMed Scopus (21) Google Scholar] ethnicity, leading us to highlight the study's inability to adjust for ethnicity as one of its limitations. With regards to the recently published meta-analysis by García-Álvarez et al. [[4]García-Álvarez M. Pineda-Tenor D. Jiménez-Sousa M.A. Fernández-Rodríguez A. Guzmán-Fulgencio M. Resino S. Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: a meta-analysis.Hepatology. 2014; 60: 1541-1550Crossref PubMed Scopus (67) Google Scholar] evaluating vitamin D status and response to hepatitis C therapy, this study differs from ours in that it includes those with HCV-HIV co-infection. Furthermore, we believe this study has significant methodological issues such as the inclusion of three studies involving the same Italian cohort of approximately 200 patients, and the exclusion of five large studies [2Kitson M.T. Dore G.J. George J. Button P. McCaughan G.W. Crawford D.H. et al.Vitamin D status does not predict sustained virologic response or fibrosis stage in chronic hepatitis C genotype 1 infection.J Hepatol. 2013; 58: 467-472Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 5Petta S. Cammà C. Scazzone C. Tripodo C. Di Marco V. Bono A. et al.Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C.Hepatology. 2010; 51: 1158-1167Crossref PubMed Scopus (358) Google Scholar, 6Lange 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. 2011; 54: 887-893Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar, 7Lange C.M. Bibert S. Kutalik Z. Burgisser P. Cerny A. Dufour J.F. et al.A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C.PLoS One. 2012; 7: e40159Crossref PubMed Scopus (49) Google Scholar, 8Grammatikos G. Lange C. Susser S. Schwendy S. Dikopoulos N. Buggisch P. et al.Vitamin D levels vary during antiviral treatment but are unable to predict treatment outcome in HCV genotype 1 infected patients.PLoS One. 2014; 9: e87974Crossref PubMed Scopus (14) Google Scholar] from Europe and Australia involving 1569 patients that were readily identifiable using the stated search strategy. Our concerns about this study have recently been published [[9]Kitson M.T. Sarrazin C. Toniutto P. Roberts S.K. Relationship between vitamin D status and response to HCV therapy.Hepatology. 2015; https://doi.org/10.1002/hep.27797Crossref PubMed Scopus (2) Google Scholar] and the validity of the study's findings should be viewed with caution. Our meta-analysis only evaluates the relationship between baseline vitamin D status and SVR. The impact of vitamin D supplementation on outcomes to interferon-based antiviral therapy, although interesting, is a different clinical question that has not been definitively assessed in prospective, randomized controlled trials. We agree that vitamin D has potential anti-viral, anti-inflammatory, anti-fibrotic and immunomodulatory actions relevant to liver disease, which have been highlighted in a number of pre-clinical studies [[10]Kitson M.T. Roberts S.K. D-livering the message: the importance of vitamin D status in chronic liver disease.J Hepatol. 2012; 57: 897-909Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar]. However high quality prospective clinical research studies are needed to support the hypothesis that vitamin D deficiency may be responsible for the worse outcomes in HCV related liver disease. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.