Vitamin D Levels Are Associated with Liver Disease Severityin Patients with Cirrhosis
Main Article Content
Keywords
cirrhosis, liver disease, serum calcium, vitamin D, vitamin D deficiency
Abstract
Vitamin D deficiency is common in advanced liver disease but its clinical significance remains controversial. The aim of this study was to examine the correlation of 25-hydryoxy vitamin D levels with liver disease severity and calcium levels in adults with cirrhosis. This cross-sectional study included 180 adults with cirrhosis enrolled in a clinical cohort study at a single university hospital. The mean age was 58.8 (±9.2) years, and cirrhosis was attributed to alcohol use in 27.2%, hepatitis C in 35.0%, non-alcoholic steatohepatitis in 27.2%, and both alcohol and hepatitis C in 10.6%. The median model for end-stage liver disease-sodium(MELD-Na) score was 12.0 (interquartile range 9.0–16.0), and mean serum albumin levels were 3.4 (±0.7) gm/dl. Median serum 25-hydroxyvitamin D levels were 28.0 (interquartile range 20–38) ng/mL, with 16 patients (8.9%) having levels <12 ng/ml and 43 (23.9%) with 25(OH)D levels <20 ng/ml. No correlation was noted between levels of 25-hydroxyvitamin D and albumin-corrected calcium in the total group and in groups stratified by vitamin D supplementation.In contrast, both serum albumin(r = 0.32; P < 0.001) and MELD-Na scores were significantly correlated with 25-hydroxyvitamin D levels (r =–0.29; P < 0.001).Correlations between 25-hydroxyvitamin D levels and serum albumin (r =−0.39; P < 0.001) and MELD-Na scores did not change substantially after excluding 67 patients receiving vitamin D supplementation (r =−0.33; P = 0.009). In conclusion, total25-hydroxyvitamin D levels correlate inversely with liver disease severity in adults with cirrhosis.
References
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22. Marroni CP, de Mello Brandao AB, Hennigen AW, Marroni C, Zanotelli ML, Cantisani G, et al. MELD scores with incorporation of serum sodium and death prediction in cirrhotic patients on the waiting list for liver transplantation: A single center experience in southern Brazil. Clin Transplant. 2012 Jul–Aug;26(4): E395–401. http://dx.doi.org/10.1111/j.1399-0012.2012.01688.x
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24. Elwir S, Lake J. Current status of liver allocation in the United States. Gastroenterol Hepatol (NY). 2016 Mar;12(3):166–70.
25. Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: National Academies Press; 2011.
26. Putz-Bankuti C, Pilz S, Stojakovic T, Scharnagl H, Pieber TR, Trauner M, et al. Association of 25-hydroxyvitamin D levels with liver dysfunction and mortality in chronic liver disease. Liver Int. 2012 May;32(5):845–51. http://dx.doi.org/10.1111/j.1478-3231.2011.02735.x
27. Monegal A, Navasa M, Guanabens N, Peris P, Pons F, Martinez de Osaba MJ, et al. Osteoporosis and bone mineral metabolism disorders in cirrhotic patients referred for orthotopic liver transplantation. Calcif Tissue Int. 1997 Feb;60(2):148–54. http://dx.doi.org/10.1007/s002239900205
28. Malham M, Jorgensen SP, Ott P, Agnholt J, Vilstrup H, Borre M, et al. Vitamin D deficiency in cirrhosis relates to liver dysfunction rather than aetiology. World J Gastroenterol. 2011 Feb 21;17(7):922–5. http://dx.doi.org/10.3748/wjg.v17.i7.922
29. Ho AS, Cheng CC, Lee SC, Liu ML, Lee JY, Wang WM, et al. Novel biomarkers predict liver fibrosis in hepatitis C patients: Alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI. J Biomed Sci. 2010 Jul 15;17:58. http://dx.doi.org/10.1186/1423-0127-17-58
30. Meier U, Gressner O, Lammert F, Gressner AM. Gc-globulIn: Roles in response to injury. Clin Chem. 2006 Jul;52(7):1247–53. http://dx.doi.org/10.1373/clinchem.2005.065680
31. Finkelmeier F, Kronenberger B, Zeuzem S, Piiper A, Waidmann O. Low 25-Hydroxyvitamin D levels are associated with infections and mortality in patients with cirrhosis. PLoS One. 2015 Jun 29;10(6):e0132119. http://dx.doi.org/10.1371/journal.pone.0132119
32. Corey RL, Whitaker MD, Crowell MD, Keddis MT, Aqel B, Balan V, et al. Vitamin D deficiency, parathyroid hormone levels, and bone disease among patients with end-stage liver disease and normal serum creatinine awaiting liver transplantation. Clin Transplant. 2014 May;28(5):579–84. http://dx.doi.org/10.1111/ctr.12351
33. Schwartz JB, Lai J, Lizaola B, Kane L, Markova S, Weyland P, et al. A comparison of measured and calculated free 25(OH) vitamin D levels in clinical populations. J Clin Endocrinol Metab. 2014 May;99(5):1631–7. http://dx.doi.org/10.1210/jc.2013-3874
34. Petta S, Camma 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 Apr;51(4):1158–67. http://dx.doi.org/10.1002/hep.23489
2. Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266–81. http://dx.doi.org/10.1056/NEJMra070553
3. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1689S–96S.
4. Hollander D, Muralidhara KS, Zimmerman A. Vitamin D-3 intestinal absorption in vivo: Influence of fatty acids, bile salts, and perfusate pH on absorption. Gut. 1978 Apr;19(4):267–72. http://dx.doi.org/10.1136/gut.19.4.267
5. Bikle DD. Vitamin D insufficiency/deficiency in gastrointestinal disorders. J Bone Miner Res. 2007 Dec;22 Suppl 2:V50–4. http://dx.doi.org/10.1359/jbmr.07s208
6. Stokes CS, Volmer DA, Grunhage F, Lammert F. Vitamin D in chronic liver disease. Liver Int. 2013 Mar;33(3):338–52. http://dx.doi.org/10.1111/liv.12106
7. Arteh J, Narra S, Nair S. Prevalence of vitamin D deficiency in chronic liver disease. Dig Dis Sci. 2010 Sep;55(9):2624–8. http://dx.doi.org/10.1007/s10620-009-1069-9
8. Fisher L, Fisher A. Vitamin D and parathyroid hormone in outpatients with noncholestatic chronic liver disease. Clin Gastroenterol Hepatol. 2007 Apr;5(4):513–20. http://dx.doi.org/10.1016/j.cgh.2006.10.015
9. Reese PP, Bloom RD, Feldman HI, Huverserian A, Thomasson A, Shults J, et al. Changes in vitamin D binding protein and vitamin D concentrations associated with liver transplantation. Liver Int. 2012 Feb;32(2):287–96. http://dx.doi.org/10.1111/j.1478-3231.2011.02638.x
10. Targher G, Byrne CD. Lower 25-hydroxyvitamin D3 levels and increased risk of liver diseases: Is there a causal link? Endocrine. 2014 Sep;47(1):3–4. http://dx.doi.org/10.1007/s12020-014-0220-3
11. Targher G, Bertolini L, Scala L, Cigolini M, Zenari L, Falezza G, 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 Sep;17(7):517–24. http://dx.doi.org/10.1016/j.numecd.2006.04.002
12. Baur K, Mertens JC, Schmitt J, Iwata R, Stieger B, Eloranta JJ, et al. Combined effect of 25-OH vitamin D plasma levels and genetic vitamin D receptor (NR 1I1) variants on fibrosis progression rate in HCV patients. Liver Int. 2012 Apr;32(4):635–43. http://dx.doi.org/10.1111/j.1478-3231.2011.02674.x
13. Kitson MT, Roberts SK. D-livering the message: The importance of vitamin D status in chronic liver disease. J Hepatol. 2012 Oct;57(4):897–909. http://dx.doi.org/10.1016/j.jhep.2012.04.033
14. Abramovitch S, Dahan-Bachar L, Sharvit E, Weisman Y, Ben Tov A, Brazowski E, et al. Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats. Gut. 2011 Dec;60(12):1728–37. http://dx.doi.org/10.1136/gut.2010.234666
15. Berg JP. Vitamin D-binding protein prevents vitamin D deficiency and presents vitamin D for its renal activation. Eur J Endocrinol. 1999 Oct;141(4):321–2. http://dx.doi.org/10.1530/eje.0.1410321
16. Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med. 2013 Nov 21;369(21):1991–2000. http://dx.doi.org/10.1056/NEJMoa1306357
17. Lai JC, Bikle DD, Lizaola B, Hayssen H, Terrault NA, Schwartz JB. Total 25(OH) vitamin D, free 25(OH) vitamin D and markers of bone turnover in cirrhotics with and without synthetic dysfunction. Liver Int. 2015 Oct;35(10):2294–300. http://dx.doi.org/10.1111/liv.12819
18. Ripoll C, Bari K, Garcia-Tsao G. Serum albumin can identify patients with compensated cirrhosis with a good prognosis. J Clin Gastroenterol. 2015 Aug;49(7):613–19. http://dx.doi.org/10.1097/MCG.0000000000000207
19. Biggins SW, Kim WR, Terrault NA, Saab S, Balan V, Schiano T, et al. Evidence-based incorporation of serum sodium concentration into MELD. Gastroenterology. 2006 May;130(6):1652–60. http://dx.doi.org/10.1053/j.gastro.2006.02.010
20. Ruf AE, Kremers WK, Chavez LL, Descalzi VI, Podesta LG, Villamil FG. Addition of serum sodium into the MELD score predicts waiting list mortality better than MELD alone. Liver Transpl. 2005 Mar;11(3):336–43. http://dx.doi.org/10.1002/lt.20329
21. Londono MC, Cardenas A, Guevara M, Quinto L, de Las Heras D, Navasa M, et al. MELD score and serum sodium in the prediction of survival of patients with cirrhosis awaiting liver transplantation. Gut. 2007 Sep;56(9):1283–90. http://dx.doi.org/10.1136/gut.2006.102764
22. Marroni CP, de Mello Brandao AB, Hennigen AW, Marroni C, Zanotelli ML, Cantisani G, et al. MELD scores with incorporation of serum sodium and death prediction in cirrhotic patients on the waiting list for liver transplantation: A single center experience in southern Brazil. Clin Transplant. 2012 Jul–Aug;26(4): E395–401. http://dx.doi.org/10.1111/j.1399-0012.2012.01688.x
23. Umemura T, Shibata S, Sekiguchi T, Kitabatake H, Nozawa Y, Okuhara S, et al. Serum sodium concentration is associated with increased risk of mortality in patients with compensated liver cirrhosis. Hepatol Res. 2015 Jul;45(7):739–44. http://dx.doi.org/10.1111/hepr.12412
24. Elwir S, Lake J. Current status of liver allocation in the United States. Gastroenterol Hepatol (NY). 2016 Mar;12(3):166–70.
25. Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: National Academies Press; 2011.
26. Putz-Bankuti C, Pilz S, Stojakovic T, Scharnagl H, Pieber TR, Trauner M, et al. Association of 25-hydroxyvitamin D levels with liver dysfunction and mortality in chronic liver disease. Liver Int. 2012 May;32(5):845–51. http://dx.doi.org/10.1111/j.1478-3231.2011.02735.x
27. Monegal A, Navasa M, Guanabens N, Peris P, Pons F, Martinez de Osaba MJ, et al. Osteoporosis and bone mineral metabolism disorders in cirrhotic patients referred for orthotopic liver transplantation. Calcif Tissue Int. 1997 Feb;60(2):148–54. http://dx.doi.org/10.1007/s002239900205
28. Malham M, Jorgensen SP, Ott P, Agnholt J, Vilstrup H, Borre M, et al. Vitamin D deficiency in cirrhosis relates to liver dysfunction rather than aetiology. World J Gastroenterol. 2011 Feb 21;17(7):922–5. http://dx.doi.org/10.3748/wjg.v17.i7.922
29. Ho AS, Cheng CC, Lee SC, Liu ML, Lee JY, Wang WM, et al. Novel biomarkers predict liver fibrosis in hepatitis C patients: Alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI. J Biomed Sci. 2010 Jul 15;17:58. http://dx.doi.org/10.1186/1423-0127-17-58
30. Meier U, Gressner O, Lammert F, Gressner AM. Gc-globulIn: Roles in response to injury. Clin Chem. 2006 Jul;52(7):1247–53. http://dx.doi.org/10.1373/clinchem.2005.065680
31. Finkelmeier F, Kronenberger B, Zeuzem S, Piiper A, Waidmann O. Low 25-Hydroxyvitamin D levels are associated with infections and mortality in patients with cirrhosis. PLoS One. 2015 Jun 29;10(6):e0132119. http://dx.doi.org/10.1371/journal.pone.0132119
32. Corey RL, Whitaker MD, Crowell MD, Keddis MT, Aqel B, Balan V, et al. Vitamin D deficiency, parathyroid hormone levels, and bone disease among patients with end-stage liver disease and normal serum creatinine awaiting liver transplantation. Clin Transplant. 2014 May;28(5):579–84. http://dx.doi.org/10.1111/ctr.12351
33. Schwartz JB, Lai J, Lizaola B, Kane L, Markova S, Weyland P, et al. A comparison of measured and calculated free 25(OH) vitamin D levels in clinical populations. J Clin Endocrinol Metab. 2014 May;99(5):1631–7. http://dx.doi.org/10.1210/jc.2013-3874
34. Petta S, Camma 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 Apr;51(4):1158–67. http://dx.doi.org/10.1002/hep.23489
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May 26, 2017
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Vitamin D Levels Are Associated with Liver Disease Severityin Patients with Cirrhosis. (2017). Journal of Renal and Hepatic Disorders, 1(2), 1-9. https://doi.org/10.15586/jrenhep.2017.15
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Original Articles Hepatology
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