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Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study

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Abstract

Vitamin D deficiency is common among patients with liver diseases. Both cholestatic and non-cholestatic liver diseases can cause vitamin D deficiency. Whether vitamin D status can also affect liver function is poorly understood. To investigate the association between vitamin D status, liver enzymes, and incident liver disease, we included a total of 2,649 individuals from the Monica10 study conducted in 1993–1994. Vitamin D status as assessed by serum 25-hydroxyvitamin, serum alanine transaminase (ALT), aspartate transaminase (AST), and gamma glutamyl transferase (GGT) were measured at baseline. Information on fatal and non-fatal liver disease was obtained from the Danish National Patient Register and The Danish Registry of Causes of Death, respectively. Median follow-up time was 16.5 years, and there were 62 incident cases of fatal and non-fatal liver disease. Multivariable Cox regression analyses with age as underlying time axis and delayed entry showed a statistically significant inverse association between vitamin D status and incident liver disease with a hazard ratio = 0.88 (95 % confidence interval 0.79–0.99) per 10 nmol/l higher vitamin D status at baseline (adjusted for gender, season, alcohol consumption, smoking, physical activity, dietary habits, education, body mass index, and ALT). The risk of having a high level of ALT, AST, or GGT tended to be higher for lower vitamin D levels, although not statistically significant. In this general population study, vitamin D status was inversely associated with incident liver disease. Further studies are needed to determine whether patients in risk of developing impaired liver function should be screened for vitamin D deficiency for preventive purposes.

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References

  1. M.F. Holick, Vitamin D deficiency. N. Engl. J. Med. 357(3), 266–281 (2007)

    Article  CAS  PubMed  Google Scholar 

  2. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, M. Fenger et al., Vitamin D status and cause-specific mortality: a general population study. PLoS ONE 7(12), e52423 (2012)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, M. Fenger et al., Vitamin D status and changes in cardiovascular risk factors: a prospective study of a general population. Cardiology 123(1), 62–70 (2012)

    Article  CAS  PubMed  Google Scholar 

  4. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, M. Fenger et al., Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study. Endocrine 43(3), 618–625 (2013)

    Article  CAS  PubMed  Google Scholar 

  5. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, K. Rasmussen et al., Vitamin D status and 5-year changes in urine albumin creatinine ratio and parathyroid hormone in a general population. Endocrine 44(2), 473–480 (2013)

    Article  CAS  PubMed  Google Scholar 

  6. T. Skaaby, L.L. Husemoen, T. Martinussen, J.P. Thyssen, M. Melgaard, B.H. Thuesen et al., Vitamin D status, filaggrin genotype, and cardiovascular risk factors: a Mendelian randomization approach. PLoS ONE 8(2), e57647 (2013)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. L.L. Husemoen, T. Skaaby, B.H. Thuesen, T. Jorgensen, R.V. Fenger, A. Linneberg, Serum 25(OH)D and incident type 2 diabetes: a cohort study. Eur. J. Clin. Nutr. 66(12), 1309–1314 (2012)

    Article  CAS  PubMed  Google Scholar 

  8. J. Arteh, S. Narra, S. Nair, Prevalence of vitamin D deficiency in chronic liver disease. Dig. Dis. Sci. 55(9), 2624–2628 (2010)

    Article  CAS  PubMed  Google Scholar 

  9. M. Malham, S.P. Jorgensen, P. Ott, J. Agnholt, H. Vilstrup, M. Borre et al., Vitamin D deficiency in cirrhosis relates to liver dysfunction rather than aetiology. World J. Gastroenterol. 17(7), 922–925 (2011)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. A. Rode, S. Fourlanos, A. Nicoll, Oral vitamin D replacement is effective in chronic liver disease. Gastroenterol. Clin. Biol. 34(11), 618–620 (2010)

    Article  CAS  PubMed  Google Scholar 

  11. S. Zuniga, D. Firrincieli, C. Housset, N. Chignard, Vitamin D and the vitamin D receptor in liver pathophysiology. Clin. Res. Hepatol. Gastroenterol. 35(4), 295–302 (2011)

    Article  CAS  PubMed  Google Scholar 

  12. H.M. Pappa, E. Bern, D. Kamin, R.J. Grand, Vitamin D status in gastrointestinal and liver disease. Curr. Opin. Gastroenterol. 24(2), 176–183 (2008)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. C. Putz-Bankuti, S. Pilz, T. Stojakovic, H. Scharnagl, T.R. Pieber, M. Trauner et al., Association of 25-hydroxyvitamin D levels with liver dysfunction and mortality in chronic liver disease. Liver Int. 32(5), 845–851 (2012)

    Article  CAS  PubMed  Google Scholar 

  14. A. Vogel, C.P. Strassburg, M.P. Manns, Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis. Hepatology 35(1), 126–131 (2002)

    Article  CAS  PubMed  Google Scholar 

  15. L. Fan, X. Tu, Y. Zhu, L. Zhou, T. Pfeiffer, R. Feltens et al., Genetic association of vitamin D receptor polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese. J. Gastroenterol. Hepatol. 20(2), 249–255 (2005)

    Article  CAS  PubMed  Google Scholar 

  16. J.J. Potter, X. Liu, A. Koteish, E. Mezey, 1,25-Dihydroxyvitamin D3 and its nuclear receptor repress human alpha(1) (I) collagen expression and type I collagen formation. Liver Int. 33(5), 677–686 (2013)

    Article  CAS  PubMed  Google Scholar 

  17. G.D. Carter, R. Carter, J. Jones, J. Berry, How accurate are assays for 25-hydroxyvitamin D? Data from the international vitamin D external quality assessment scheme. Clin. Chem. 50(11), 2195–2197 (2004)

    Article  CAS  PubMed  Google Scholar 

  18. T.F. Andersen, M. Madsen, J. Jorgensen, L. Mellemkjoer, J.H. Olsen, The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan. Med. Bull. 46(3), 263–268 (1999)

    CAS  PubMed  Google Scholar 

  19. K. Juel, K. Helweg-Larsen, The Danish registers of causes of death. Dan. Med. Bull. 46(4), 354–357 (1999)

    CAS  PubMed  Google Scholar 

  20. M. Osler, B.L. Heitmann, S. Hoidrup, L.M. Jorgensen, M. Schroll, Food intake patterns, self rated health and mortality in Danish men and women. A prospective observational study. J. Epidemiol. Commun. Health 55(6), 399–403 (2001)

    Article  CAS  Google Scholar 

  21. Liver disease in Europe. Lancet. 381(9866), 508 (2013)

    Google Scholar 

  22. M. Heron, Deaths: leading causes for 2004. Natl. Vital. Stat. Rep. 56(5), 1–95 (2007)

    PubMed  Google Scholar 

  23. F.A. Rochling, Evaluation of abnormal liver tests. Clin. Cornerstone 3(6), 1–12 (2001)

    Article  CAS  PubMed  Google Scholar 

  24. C.E. Ruhl, J.E. Everhart, Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology 136(2), 477–485 (2009)

    Article  CAS  PubMed  Google Scholar 

  25. L. Wang, J. Zhang, B. Wang, Y. Zhang, J. Hong, Y. Zhang, et al. New evidence for an association between liver enzymes and pancreatic islet β-cell dysfunction in young obese patients. Endocrine. (2013). doi:10.1007/s12020-013-9937-7

  26. Y.N. Flores, H.F. Yee Jr, M. Leng, J.J. Escarce, R. Bastani, J. Salmeron et al., Risk factors for chronic liver disease in Blacks, Mexican Americans, and Whites in the United States: results from NHANES IV, 1999–2004. Am. J. Gastroenterol. 103(9), 2231–2238 (2008)

    Article  PubMed  Google Scholar 

  27. J. Arteh, S. Narra, S. Nair, Prevalence of vitamin D deficiency in chronic liver disease. Dig. Dis. Sci. 55(9), 2624–2628 (2010)

    Article  CAS  PubMed  Google Scholar 

  28. L. Fisher, A. Fisher, Vitamin D and parathyroid hormone in outpatients with noncholestatic chronic liver disease. Clin. Gastroenterol. Hepatol. 5(4), 513–520 (2007)

    Article  CAS  PubMed  Google Scholar 

  29. R. Bouillon, G. Carmeliet, L. Verlinden, E.E. van, E.E. Verstuyf, H.F. Luderer et al., Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr. Rev. 29(6), 726–776 (2008)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. D.D. Bikle, Vitamin D insufficiency/deficiency in gastrointestinal disorders. J. Bone Miner. Res. 22(Suppl 2), V50–V54 (2007)

    Article  CAS  PubMed  Google Scholar 

  31. S. Petta, C. Camma, C. Scazzone, C. Tripodo, M.V. Di, A. Bono 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 51(4), 1158–1167 (2010)

    Article  CAS  PubMed  Google Scholar 

  32. E. Scorletti, P.C. Calder, C.D. Byrne, Non-alcoholic fatty liver disease and cardiovascular risk: metabolic aspects and novel treatments. Endocrine 40(3), 332–343 (2011)

    Article  CAS  PubMed  Google Scholar 

  33. Y. Colak, E. Senates, A. Yesil, Y. Yilmaz, O. Ozturk, L. Doganay et al., Assessment of endothelial function in patients with nonalcoholic fatty liver disease. Endocrine 43(1), 100–107 (2013)

    Article  CAS  PubMed  Google Scholar 

  34. G. Targher, L. Bertolini, L. Scala, M. Cigolini, L. Zenari, G. Falezza et al., Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr. Metab. Cardiovasc. Dis. 17(7), 517–524 (2007)

    Article  CAS  PubMed  Google Scholar 

  35. I. Barchetta, F. Angelico, B.M. Del, M.G. Baroni, P. Pozzilli, S. Morini et al., Strong association between non-alcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes. BMC Med. 9, 85 (2011)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. B. Thuesen, L. Husemoen, M. Fenger, J. Jakobsen, P. Schwarz, U. Toft et al., Determinants of vitamin D status in a general population of Danish adults. Bone 50(3), 605–610 (2012)

    Article  CAS  PubMed  Google Scholar 

  37. W.B. Grant, Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level: implications for meta-analyses and setting vitamin D guidelines. Dermatoendocrinology 3(3), 199–204 (2011)

    CAS  Google Scholar 

  38. W.B. Grant, Effect of follow-up time on the relation between prediagnostic serum 25-hydroxyvitamin D and all-cause mortality rate. Dermatoendocrinology 4(2), 198–202 (2012)

    Article  CAS  Google Scholar 

  39. R. Jorde, M. Sneve, M. Hutchinson, N. Emaus, Y. Figenschau, G. Grimnes, Tracking of serum 25-hydroxyvitamin D levels during 14 years in a population-based study and during 12 months in an intervention study. Am. J. Epidemiol. 171(8), 903–908 (2010)

    Article  PubMed  Google Scholar 

  40. K.E. Corey, H. Zheng, J. Mendez-Navarro, A. Delgado-Borrego, J.L. Dienstag, R.T. Chung, Serum vitamin D levels are not predictive of the progression of chronic liver disease in hepatitis C patients with advanced fibrosis. PLoS ONE 7(2), e27144 (2012)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. S.J. Weintraub, J.F. Fleckenstein, T.N. Marion, M.A. Madey, T.M. Mahmoudi, K.B. Schechtman, Vitamin D and the racial difference in the genotype 1 chronic hepatitis C treatment response. Am. J. Clin. Nutr. 96(5), 1025–1031 (2012)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. D.L. White, S. Tavakoli-Tabasi, F. Kanwal, D.J. Ramsey, A. Hashmi, J. Kuzniarek et al., The association between serological and dietary vitamin D levels and hepatitis C-related liver disease risk differs in African American and white males. Aliment. Pharmacol. Ther. 38(1), 28–37 (2013)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Research Centre for Prevention and Health, Glostrup Hospital, Nordre Ringvej 57, 2600, Glostrup, Denmark

    Tea Skaaby, Lise Lotte Nystrup Husemoen, Anders Borglykke, Torben Jørgensen, Betina Heinsbæk Thuesen, Charlotta Pisinger & Allan Linneberg

  2. Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark

    Torben Jørgensen

  3. Faculty of Medicine, Ålborg University, Ålborg, Denmark

    Torben Jørgensen

  4. Department of Internal Medicine, Glostrup University Hospital, Glostrup, Denmark

    Lars Ebbe Schmidt

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  1. Tea Skaaby
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  2. Lise Lotte Nystrup Husemoen
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  8. Allan Linneberg
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Correspondence to Tea Skaaby.

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Skaaby, T., Husemoen, L.L.N., Borglykke, A. et al. Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study. Endocrine 47, 213–220 (2014). https://doi.org/10.1007/s12020-013-0107-8

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  • DOI: https://doi.org/10.1007/s12020-013-0107-8

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