Endocrine

, Volume 47, Issue 1, pp 213–220 | Cite as

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

  • Tea Skaaby
  • Lise Lotte Nystrup Husemoen
  • Anders Borglykke
  • Torben Jørgensen
  • Betina Heinsbæk Thuesen
  • Charlotta Pisinger
  • Lars Ebbe Schmidt
  • Allan Linneberg
Original Article

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.

Keywords

Vitamin D Liver disease Liver enzymes Alanine transaminase (ALT) Aspartate transaminase (AST) Gamma glutamyl transferase (GGT) 

References

  1. 1.
    M.F. Holick, Vitamin D deficiency. N. Engl. J. Med. 357(3), 266–281 (2007)PubMedCrossRefGoogle Scholar
  2. 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)PubMedCentralPubMedCrossRefGoogle Scholar
  3. 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)PubMedCrossRefGoogle Scholar
  4. 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)PubMedCrossRefGoogle Scholar
  5. 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)PubMedCrossRefGoogle Scholar
  6. 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)PubMedCentralPubMedCrossRefGoogle Scholar
  7. 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)PubMedCrossRefGoogle Scholar
  8. 8.
    J. Arteh, S. Narra, S. Nair, Prevalence of vitamin D deficiency in chronic liver disease. Dig. Dis. Sci. 55(9), 2624–2628 (2010)PubMedCrossRefGoogle Scholar
  9. 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)PubMedCentralPubMedCrossRefGoogle Scholar
  10. 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)PubMedCrossRefGoogle Scholar
  11. 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)PubMedCrossRefGoogle Scholar
  12. 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)PubMedCentralPubMedCrossRefGoogle Scholar
  13. 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)PubMedCrossRefGoogle Scholar
  14. 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)PubMedCrossRefGoogle Scholar
  15. 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)PubMedCrossRefGoogle Scholar
  16. 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)PubMedCrossRefGoogle Scholar
  17. 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)PubMedCrossRefGoogle Scholar
  18. 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)PubMedGoogle Scholar
  19. 19.
    K. Juel, K. Helweg-Larsen, The Danish registers of causes of death. Dan. Med. Bull. 46(4), 354–357 (1999)PubMedGoogle Scholar
  20. 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)CrossRefGoogle Scholar
  21. 21.
    Liver disease in Europe. Lancet. 381(9866), 508 (2013)Google Scholar
  22. 22.
    M. Heron, Deaths: leading causes for 2004. Natl. Vital. Stat. Rep. 56(5), 1–95 (2007)PubMedGoogle Scholar
  23. 23.
    F.A. Rochling, Evaluation of abnormal liver tests. Clin. Cornerstone 3(6), 1–12 (2001)PubMedCrossRefGoogle Scholar
  24. 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)PubMedCrossRefGoogle Scholar
  25. 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. 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)PubMedCrossRefGoogle Scholar
  27. 27.
    J. Arteh, S. Narra, S. Nair, Prevalence of vitamin D deficiency in chronic liver disease. Dig. Dis. Sci. 55(9), 2624–2628 (2010)PubMedCrossRefGoogle Scholar
  28. 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)PubMedCrossRefGoogle Scholar
  29. 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)PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    D.D. Bikle, Vitamin D insufficiency/deficiency in gastrointestinal disorders. J. Bone Miner. Res. 22(Suppl 2), V50–V54 (2007)PubMedCrossRefGoogle Scholar
  31. 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)PubMedCrossRefGoogle Scholar
  32. 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)PubMedCrossRefGoogle Scholar
  33. 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)PubMedCrossRefGoogle Scholar
  34. 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)PubMedCrossRefGoogle Scholar
  35. 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)PubMedCentralPubMedCrossRefGoogle Scholar
  36. 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)PubMedCrossRefGoogle Scholar
  37. 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)Google Scholar
  38. 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)CrossRefGoogle Scholar
  39. 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)PubMedCrossRefGoogle Scholar
  40. 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)PubMedCentralPubMedCrossRefGoogle Scholar
  41. 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)PubMedCentralPubMedCrossRefGoogle Scholar
  42. 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)PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Tea Skaaby
    • 1
  • Lise Lotte Nystrup Husemoen
    • 1
  • Anders Borglykke
    • 1
  • Torben Jørgensen
    • 1
    • 2
    • 3
  • Betina Heinsbæk Thuesen
    • 1
  • Charlotta Pisinger
    • 1
  • Lars Ebbe Schmidt
    • 4
  • Allan Linneberg
    • 1
  1. 1.Research Centre for Prevention and HealthGlostrup HospitalGlostrupDenmark
  2. 2.Faculty of Health ScienceUniversity of CopenhagenCopenhagenDenmark
  3. 3.Faculty of MedicineÅlborg UniversityÅlborgDenmark
  4. 4.Department of Internal MedicineGlostrup University HospitalGlostrupDenmark

Personalised recommendations