Skip to main content

Advertisement

Log in

Vitamin D Deficiency in Patients with Chronic Liver Disease and Cirrhosis

  • Liver (BR Bacon, Section Editor)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Vitamin D is now widely recognized to have multiple extraskeletal health functions. The liver is one of the major organs involved in its metabolism. Recent studies have demonstrated a very high prevalence of vitamin D deficiency and insufficiency in patients with chronic liver disease and cirrhosis. There is an emerging interest to explore the relationship between vitamin D deficiency and prevalence and severity of non-alcoholic liver disease and response to antiviral therapy in hepatitis C. In this review, we discuss the current status of our understanding of vitamin D metabolism and vitamin D deficiency in patients with chronic liver disease and cirrhosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008;8(9):685–98.

    Article  PubMed  CAS  Google Scholar 

  2. Cantorna MT, Mahon BD. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med (Maywood). 2004;229(11):1136–42.

    CAS  Google Scholar 

  3. Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev. 2005;26(5):662–87.

    Article  PubMed  CAS  Google Scholar 

  4. Timms PM, Mannan N, Hitman GA, et al. Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM. 2002;95(12):787–96.

    Article  PubMed  CAS  Google Scholar 

  5. Wortsman J, Matsuoka LY, Chen TC, et al. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72(3):690–3.

    PubMed  CAS  Google Scholar 

  6. Blum M, Dallal GE, Dawson-Hughes B. Body size and serum 25 hydroxy vitamin D response to oral supplements in healthy older adults. J Am Coll Nutr. 2008;27(2):274–9.

    PubMed  CAS  Google Scholar 

  7. Weisman Y, Harell A, Edelstein S, et al. 1 alpha, 25-Dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in vitro synthesis by human decidua and placenta. Nature. 1979;281(5729):317–9.

    Article  PubMed  CAS  Google Scholar 

  8. Gray TK, Lester GE, Lorenc RS. Evidence for extra-renal 1 alpha-hydroxylation of 25-hydroxyvitamin D3 in pregnancy. Science. 1979;204(4399):1311–3.

    Article  PubMed  CAS  Google Scholar 

  9. Stoffels K, Overbergh L, Bouillon R, et al. Immune regulation of 1alpha-hydroxylase in murine peritoneal macrophages: unravelling the IFNgamma pathway. J Steroid Biochem Mol Biol. 2007;103(3–5):567–71.

    Article  PubMed  CAS  Google Scholar 

  10. Holick MF. Vitamin D: a millenium perspective. J Cell Biochem. 2003;88(2):296–307.

    Article  PubMed  CAS  Google Scholar 

  11. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87(4):1080S–6S.

    PubMed  CAS  Google Scholar 

  12. WHO. WHO scientific group on the prevention and management of osteoporosis. Prevention and management of osteoporosis: report of a WHO scientific group. Geneva: World Health Organization; 2003.

    Google Scholar 

  13. Rosen CJ: Clinical practice. Vitamin D insufficiency. N Engl J Med 2011, 364(3):248–54. A state-of the art review of the topic by an expert in the field. This details current understanding of vitamin D metabolism, its role in various extra-bone conditions and mechanisms, and replacement recommendation.

    Article  PubMed  CAS  Google Scholar 

  14. • IOM (Institute of Medicine) Dietary reference intakes for calcium and vitamin D.Washington, DC: Institute of Medicine, 2011 (http://www.iom.edu/vitaminD.). A long awaited report from the IOM. It updated the defintions of vitamin D deficiency and insufficiency impacting the prevalence and replacement recommendations.

  15. Heaney RP. The vitamin D requirement in health and disease. J Steroid Biochem Mol Biol. 2005;97(1–2):13–9.

    Article  PubMed  CAS  Google Scholar 

  16. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.

    Article  PubMed  CAS  Google Scholar 

  17. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81(3):353–73.

    Article  PubMed  CAS  Google Scholar 

  18. Steingrimsdottir L, Gunnarsson O, Indridason OS, et al. Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake. JAMA. 2005;294(18):2336–41.

    Article  PubMed  CAS  Google Scholar 

  19. •• Fisher L, Fisher A: Vitamin D and parathyroid hormone in outpatients with noncholestatic chronic liver disease. Clin Gastroenterol Hepatol 2007, 5(4):513–20. This is the most comprehensive study done to date to examine the prevalence and predictors of vitamin D insufficiency and deficiency in patients with chronic liver disease.

    Article  PubMed  CAS  Google Scholar 

  20. • Arteh J, Narra S, Nair S: Prevalence of vitamin D deficiency in chronic liver disease. Dig Dis Sci 2010, 55(9):2624–8. This prospective study examined the prevalence and predictors of vitamin D insufficiency and deficiency in US patients with chronic liver disease.

    Article  PubMed  CAS  Google Scholar 

  21. Miroliaee A, Nasiri-Toosi M, Khalilzadeh O, et al. Disturbances of parathyroid hormone-vitamin D axis in non-cholestatic chronic liver disease: a cross-sectional study. Hepatol Int. 2010;4(3):634–40.

    Article  PubMed  Google Scholar 

  22. Wills MR, Savory J. Vitamin D metabolism and chronic liver disease. Ann Clin Lab Sci. 1984;14(3):189–97.

    PubMed  CAS  Google Scholar 

  23. Heaf JG. Hepatic osteodystrophy. Scand J Gastroenterol. 1985;20(9):1035–40.

    Article  PubMed  CAS  Google Scholar 

  24. American Gastroenterological Association medical position statement: osteoporosis in hepatic disorders. Gastroenterology. 2003; 125(3):937–40.

    Google Scholar 

  25. Cheng JB, Levine MA, Bell NH, et al. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A. 2004;101(20):7711–5.

    Article  PubMed  CAS  Google Scholar 

  26. Michaud J, Naud J, Ouimet D, et al. Reduced hepatic synthesis of calcidiol in uremia. J Am Soc Nephrol. 2010;21(9):1488–97.

    Article  PubMed  CAS  Google Scholar 

  27. Hepner GW, Roginsky M, Moo HF. Abnormal vitamin D metabolism in patients with cirrhosis. Am J Dig Dis. 1976;21(7):527–32.

    Article  PubMed  CAS  Google Scholar 

  28. Wagonfeld JB, Nemchausky BA, Bolt M, et al. Comparison of vitamin D and 25-hydroxy-vitamin-D in the therapy of primary biliary cirrhosis. Lancet. 1976;2(7982):391–4.

    Article  PubMed  CAS  Google Scholar 

  29. Jung RT, Davie M, Hunter JO, et al. Abnormal vitamin D metabolism in cirrhosis. Gut. 1978;19(4):290–3.

    Article  PubMed  CAS  Google Scholar 

  30. Danielsson A, Lorentzon R, Larsson SE. Intestinal absorption and 25-hydroxylation of vitamin D in patients with primary biliary cirrhosis. Scand J Gastroenterol. 1982;17(3):349–55.

    Article  PubMed  CAS  Google Scholar 

  31. Chiu KC, Chu A, Go VL, et al. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. 2004;79(5):820–5.

    PubMed  CAS  Google Scholar 

  32. Ford ES, Ajani UA, McGuire LC, et al. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care. 2005;28(5):1228–30.

    Article  PubMed  CAS  Google Scholar 

  33. Pittas AG, Lau J, Hu FB, et al. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92(6):2017–29.

    Article  PubMed  CAS  Google Scholar 

  34. Ybarra J, Sanchez-Hernandez J, Perez A. Hypovitaminosis D and morbid obesity. Nurs Clin North Am. 2007;42(1):19–27.

    Article  PubMed  Google Scholar 

  35. • Liangpunsakul S, Chalasani N: Serum Vitamin D Concentrations and Unexplained Elevation in ALT Among US Adults. Dig Dis Sci 2011, 56(7):2124–9. This study examined the relationship between vitamin D levels and unexplained elevation in ALT in the general population.

    Article  PubMed  CAS  Google Scholar 

  36. Temitope F, Chalasani N, Liangpunsakul S, et al.: The association of serum vitamin D concentrations and Non Alcoholic Fatty Liver Disease (NAFLD): the multi ethnic study of atherosclerosis. american association for the study of liver diseases, The Liver Meeting 2011 San Francisco, Abstract 1625. 2011.

  37. Blum M, Dolnikowski G, Seyoum E, et al. Vitamin D(3) in fat tissue. Endocrine. 2008;33(1):90–4.

    Article  PubMed  CAS  Google Scholar 

  38. DiGiorgi M, Daud A, Inabnet WB, et al. Markers of bone and calcium metabolism following gastric bypass and laparoscopic adjustable gastric banding. Obes Surg. 2008;18(9):1144–8.

    Article  PubMed  Google Scholar 

  39. Bruno C, Fulford AD, Potts JR, et al. Serum markers of bone turnover are increased at six and 18 months after Roux-en-Y bariatric surgery: correlation with the reduction in leptin. J Clin Endocrinol Metab. 2010;95(1):159–66.

    Article  PubMed  CAS  Google Scholar 

  40. Pramyothin P, Biancuzzo RM, Lu Z, et al.: Vitamin D in adipose tissue and serum 25-hydroxyvitamin D after Roux-en-Y gastric bypass. Obesity (Silver Spring). 2011.

  41. Takiishi T, Gysemans C, Bouillon R, et al. Vitamin D and diabetes. Endocrinol Metab Clin North Am. 2010;39(2):419–46. table of contents.

    Article  PubMed  CAS  Google Scholar 

  42. Vaidya A, Williams JS, Forman JP: The independent association between 25-hydroxyvitamin D and adiponectin and its relation with BMI in two large cohorts: the NHS and the HPFS. Obesity (Silver Spring). 2011.

  43. Geier A. Shedding new light on vitamin D and fatty liver disease. J Hepatol. 2011;55(2):273–5.

    Article  PubMed  Google Scholar 

  44. • Targher G, Bertolini L, Scala L, et al.: Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 2007, 17(7):517–24. Important study that suggests that low vitamin D levels are associated with fibrosis in patients with NAFLD.

    Article  PubMed  CAS  Google Scholar 

  45. Nakano T, Cheng YF, Lai CY, et al.: Impact of artificial sunlight therapy on the progress of non-alcoholic fatty liver disease in rats. J Hepatol 2010.

  46. Beilfuss BA, Gieseler R, Zahn A: Intriguing relationship between vitamin D and liver fibrosis. 46th Annual Meeting of the European Association for the Study of the Liver Abstract #802April 17th 2010.

  47. Selmi C, Mayo MJ, Bach N, et al. Primary biliary cirrhosis in monozygotic and dizygotic twins: genetics, epigenetics, and environment. Gastroenterology. 2004;127(2):485–92.

    Article  PubMed  Google Scholar 

  48. •• D’Aldebert E, Biyeyeme Bi Mve MJ, Mergey M, et al.: Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium. Gastroenterology 2009, 136(4):1435–43. Intriguing study of potential role for vitamin D in the treatment of cholestatic liver disease.

    Article  PubMed  Google Scholar 

  49. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol. 2004;75(1):39–48.

    Article  PubMed  Google Scholar 

  50. Wang TT, Nestel FP, Bourdeau V, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173(5):2909–12.

    PubMed  CAS  Google Scholar 

  51. Collier JD, Ninkovic M, Compston JE. Guidelines on the management of osteoporosis associated with chronic liver disease. Gut. 2002;50 Suppl 1:i1–9.

    Article  PubMed  Google Scholar 

  52. Lindor KD, Gershwin ME, Poupon R, et al. Primary biliary cirrhosis. Hepatology. 2009;50(1):291–308.

    Article  PubMed  Google Scholar 

  53. Chapman R, Fevery J, Kalloo A, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010;51(2):660–78.

    Article  PubMed  CAS  Google Scholar 

  54. Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci U S A. 1996;93(15):7861–4.

    Article  PubMed  CAS  Google Scholar 

  55. Cantorna MT, Zhu Y, Froicu M, et al. Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr. 2004;80(6 Suppl):1717S–20S.

    PubMed  CAS  Google Scholar 

  56. Hypponen E, Laara E, Reunanen A, et al. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001;358(9292):1500–3.

    Article  PubMed  CAS  Google Scholar 

  57. Bikle DD. Vitamin D and immune function: understanding common pathways. Curr Osteoporos Rep. 2009;7(2):58–63.

    Article  PubMed  Google Scholar 

  58. • Hu XD, Jiang SL, Liu CH, et al.: Preventive effects of 1,25-(OH)2VD3 against ConA-induced mouse hepatitis through promoting vitamin D receptor gene expression. Acta Pharmacol Sin 2010, 31(6):703–8. Intriguing study of vitamin D as an immune-modulating agent in autoimmune hepatitis.

    Article  PubMed  CAS  Google Scholar 

  59. van der Poorten D, George J. Disease-specific mechanisms of fibrosis: hepatitis C virus and nonalcoholic steatohepatitis. Clin Liver Dis. 2008;12(4):805–24. ix.

    Article  PubMed  Google Scholar 

  60. Shen L. Vitamin D controls T cell activation: implication for causal association between vitamin D deficiency and fibrosis in chronic hepatitis C. Hepatology. 2010;52(5):1864.

    Article  PubMed  Google Scholar 

  61. Lange CM, Bojunga J, Ramos-Lopez E, 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(5):887–93.

    Article  PubMed  CAS  Google Scholar 

  62. Redaelli CA, Wagner M, Tien YH, et al. 1 alpha,25-Dihydroxycholecalciferol reduces rejection and improves survival in rat liver allografts. Hepatology. 2001;34(5):926–34.

    Article  PubMed  CAS  Google Scholar 

  63. •• Holick MF, Binkley NC, Bischoff-Ferrari HA, et al.: Evaluation, treatment, and prevention of vitamin d deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011, 96(7):1911–30. An excellent practice guideline for the management of vitamin D deficiency.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by K24 DK069290A to N.C.

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Naga Chalasani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lim, L.Y., Chalasani, N. Vitamin D Deficiency in Patients with Chronic Liver Disease and Cirrhosis. Curr Gastroenterol Rep 14, 67–73 (2012). https://doi.org/10.1007/s11894-011-0231-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-011-0231-7

Keywords

Navigation