A Genetic Validation Study Reveals a Role of Vitamin D Metabolism in the Response to Interferon-alfa-based Therapy of Chronic Hepatitis C

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Jul 19

PMID 22808108

Citations 26

Authors

Christian M Lange

Stephanie Bibert

Zoltan Kutalik

Philippe Burgisser

Andreas Cerny

Jean-Francois Dufour

Andreas Geier

Tilman J Gerlach

Markus H Heim

Raffaele Malinverni

Francesco Negro

Stephan Regenass

Klaus Badenhoop

Jorg Bojunga

Christoph Sarrazin

Stefan Zeuzem

Tobias Muller

Thomas Berg

Pierre-Yves Bochud

Darius Moradpour

Affiliations

Soon will be listed here.

Abstract

Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C.

Methodology/principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D(3) (25[OH]D(3)) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061-2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D(3)<20 ng/mL) during all seasons, but 25(OH)D(3) serum levels were not associated with treatment outcome.

Conclusions/significance: Our study suggests a role of bioactive vitamin D (1,25[OH](2)D(3), calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D(3) is not a suitable predictor of treatment outcome.

Citing Articles

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A Network-Based Analysis Reveals the Mechanism Underlying Vitamin D in Suppressing Cytokine Storm and Virus in SARS-CoV-2 Infection.

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References

von Essen M, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C . Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat Immunol. 2010; 11(4):344-9. DOI: 10.1038/ni.1851. View

Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S . Telaprevir for retreatment of HCV infection. N Engl J Med. 2011; 364(25):2417-28. DOI: 10.1056/NEJMoa1013086. View

Poordad F, McCone Jr J, Bacon B, Bruno S, Manns M, Sulkowski M . Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011; 364(13):1195-206. PMC: 3766849. DOI: 10.1056/NEJMoa1010494. View

Prasad L, Masserey Spicher V, Zwahlen M, Rickenbach M, Helbling B, Negro F . Cohort Profile: the Swiss Hepatitis C Cohort Study (SCCS). Int J Epidemiol. 2007; 36(4):731-7. DOI: 10.1093/ije/dym096. View

Martineau A, Timms P, Bothamley G, Hanifa Y, Islam K, Claxton A . High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 2011; 377(9761):242-50. PMC: 4176755. DOI: 10.1016/S0140-6736(10)61889-2. View

Lange C, Zeuzem S . IL28B single nucleotide polymorphisms in the treatment of hepatitis C. J Hepatol. 2011; 55(3):692-701. DOI: 10.1016/j.jhep.2011.03.006. View

Thompson A, Muir A, Sulkowski M, Ge D, Fellay J, Shianna K . Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology. 2010; 139(1):120-9.e18. DOI: 10.1053/j.gastro.2010.04.013. View

Rosen C . Clinical practice. Vitamin D insufficiency. N Engl J Med. 2011; 364(3):248-54. DOI: 10.1056/NEJMcp1009570. View

Lange C, Kutalik Z, Morikawa K, Bibert S, Cerny A, Dollenmaier G . Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy. Hepatology. 2011; 55(4):1038-47. DOI: 10.1002/hep.24787. View

10.

Clifton-Bligh R, Nguyen T, Au A, Bullock M, Cameron I, Cumming R . Contribution of a common variant in the promoter of the 1-α-hydroxylase gene (CYP27B1) to fracture risk in the elderly. Calcif Tissue Int. 2010; 88(2):109-16. PMC: 3030947. DOI: 10.1007/s00223-010-9434-4. View

11.

Bailey R, Cooper J, Zeitels L, Smyth D, Yang J, Walker N . Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes. 2007; 56(10):2616-21. PMC: 2493063. DOI: 10.2337/db07-0652. View

12.

Hofer H, Bankl H, Wrba F, Steindl-Munda P, Peck-Radosavljevic M, Osterreicher C . Hepatocellular fat accumulation and low serum cholesterol in patients infected with HCV-3a. Am J Gastroenterol. 2002; 97(11):2880-5. DOI: 10.1111/j.1572-0241.2002.07056.x. View

13.

Bitetto D, Fattovich G, Fabris C, Ceriani E, Falleti E, Fornasiere E . Complementary role of vitamin D deficiency and the interleukin-28B rs12979860 C/T polymorphism in predicting antiviral response in chronic hepatitis C. Hepatology. 2011; 53(4):1118-26. DOI: 10.1002/hep.24201. View

14.

Zeuzem S, Berg T, Moeller B, Hinrichsen H, Mauss S, Wedemeyer H . Expert opinion on the treatment of patients with chronic hepatitis C. J Viral Hepat. 2008; 16(2):75-90. PMC: 2759987. DOI: 10.1111/j.1365-2893.2008.01012.x. View

15.

Lange C, von Wagner M, Bojunga J, Berg T, Farnik H, Hassler A . Serum lipids in European chronic HCV genotype 1 patients during and after treatment with pegylated interferon-α-2a and ribavirin. Eur J Gastroenterol Hepatol. 2010; 22(11):1303-7. DOI: 10.1097/MEG.0b013e32833de92c. View

16.

Ge D, Fellay J, Thompson A, Simon J, Shianna K, Urban T . Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009; 461(7262):399-401. DOI: 10.1038/nature08309. View

17.

Jacobson I, McHutchison J, Dusheiko G, Di Bisceglie A, Reddy K, Bzowej N . Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011; 364(25):2405-16. DOI: 10.1056/NEJMoa1012912. View

18.

Milazzo L, Mazzali C, Bestetti G, Longhi E, Foschi A, Viola A . Liver-related factors associated with low vitamin D levels in HIV and HIV/HCV coinfected patients and comparison to general population. Curr HIV Res. 2011; 9(3):186-93. DOI: 10.2174/157016211795945269. View

19.

Lange C, Bojunga J, Ramos-Lopez E, von Wagner M, Hassler A, Vermehren J . 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(5):887-93. DOI: 10.1016/j.jhep.2010.08.036. View

20.

Lange C, Moradpour D, Doehring A, Lehr H, Mullhaupt B, Bibert S . Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection. J Hepatol. 2010; 55(2):322-7. DOI: 10.1016/j.jhep.2010.10.037. View