Vitamin D deficiency in chronic liver disease

World Journal of Hepatology

Volumn 6, Issue 12, 2014, Pages 901-915

  Iruzubieta, Paula ^a   Terán, Álvaro ^a   Crespo, Javier ^a   Fábrega, Emilio ^a  

^a HOSPITAL UNIVERSITARIO MARQUÉS DE VALDECILLA   (Spain)

Author keywords

Cholecalciferol; Hepatitis C; Interferon; Liver disease; Liver fibrosis; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Sustained virological response; Vitamin D

Indexed keywords

EID: 84920055682     PISSN: None     EISSN: 19485182     Source Type: Journal    
DOI: 10.4254/wjh.v6.i12.901     Document Type: Review

References (196)

1. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266-281 [PMID: 17634462].
2. Holick MF. Vitamin D: evolutionary, physiological and health perspectives. Curr Drug Targets 2011; 12: 4-18 [PMID: 20795941].
3. Looker AC, Dawson-Hughes B, Calvo MS, Gunter EW, Sahyoun NR. Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone 2002; 30: 771-777 [PMID: 11996918].
4. Fisher L, Fisher A. Vitamin D and parathyroid hormone in outpatients with noncholestatic chronic liver disease. Clin Gastroenterol Hepatol 2007; 5: 513-520 [PMID: 17222588].
5. Arteh J, Narra S, Nair S. Prevalence of vitamin D deficiency in chronic liver disease. Dig Dis Sci 2010; 55: 2624-2628 [PMID: 19960254 DOI: 10.1007/s10620-009-1069-9].
6. Pérez-López FR. Vitamin D and its implications for musculoskeletal health in women: an update. Maturitas 2007; 58: 117-137 [PMID: 17604580].
7. Looker AC, Mussolino ME. Serum 25-hydroxyvitamin D and hip fracture risk in older U.S. white adults. J Bone Miner Res 2008; 23: 143-150 [PMID: 17907920].
8. Peterlik M, Cross HS. Vitamin D and calcium deficits predispose for multiple chronic diseases. Eur J Clin Invest 2005; 35 290-304 [PMID: 15860041].
9. Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 2005; 26: 662-687 [PMID: 15798098].
10. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004; 80: 1689S-1696S [PMID: 15585789].
11. Heaney RP. The Vitamin D requirement in health and disease. J Steroid Biochem Mol Biol 2005; 97: 13-19 [PMID: 16026981].
12. Yamamoto N, Homma S. Vitamin D3 binding protein (group-specific component) is a precursor for the macrophage-activating signal factor from lysophosphatidylcholine-treated lymphocytes. Proc Natl Acad Sci USA 1991; 88: 8539-8543 [PMID: 1924312].
13. Metcalf JP, Thompson AB, Gossman GL, Nelson KJ, Koyama S, Rennard SI, Robbins RA. Gcglobulin functions as a cochemotaxin in the lower respiratory tract. A potential mechanism for lung neutrophil recruitment in cigarette smokers. Am Rev Respir Dis 1991; 143: 844-849 [PMID: 2008995].
14. Townsend K, Evans KN, Campbell MJ, Colston KW, Adams JS, Hewison M. Biological actions of extra-renal 25-hydroxyvitamin D-1alpha-hydroxylase and implications for chemoprevention and treatment. J Steroid Biochem Mol Biol 2005; 97: 103-109 [PMID: 16081283].
15. Akeno N, Saikatsu S, Kawane T, Horiuchi N. Mouse vitamin D-24-hydroxylase: molecular cloning, tissue distribution, and transcriptional regulation by 1alpha,25-dihydroxyvitamin D3. Endocrinology 1997; 138: 2233-2240 [PMID: 9165006].
16. Messa P, Alfieri C, Rastaldi MP. Recent insights into vitamin D and its receptor. J Nephrol 2011; 24 Suppl 18: S30-S37 [PMID: 21623580].
17. Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, Handunnetthi L, Handel AE, Disanto G, Orton SM, Watson CT, Morahan JM, Giovannoni G, Ponting CP, Ebers GC, Knight JC. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res 2010; 20: 1352-1360 [PMID: 20736230 DOI: 10.1101/gr.107920.110].
18. Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 2006; 126: 789-799 [PMID: 16923397].
19. Van Belle TL, Gysemans C, Mathieu C. Vitamin D in autoimmune, infectious and allergic diseases: a vital player? Best Pract Res Clin Endocrinol Metab 2011; 25: 617-632 [PMID: 21872803].
20. 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: 685-698 [PMID: 19172691].
21. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. The role of vitamin D in cancer prevention. Am J Public Health 2006; 96: 252-261 [PMID: 16380576].
22. Vacek JL, Vanga SR, Good M, Lai SM, Lakkireddy D, Howard PA. Vitamin D deficiency and supplementation and relation to cardiovascular health. Am J Cardiol 2012; 109: 359-363 [PMID: 22071212 DOI: 10.1016/j.amjcard.2011.09.020].
23. Mathieu C, Badenhoop K. Vitamin D and type 1 diabetes mellitus: state of the art. Trends Endocrinol Metab 2005; 16: 261-266 [PMID: 15996876].
24. Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, Hu FB. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care 2013; 36: 1422-1428 [PMID: 23613602 DOI: 102337/dc12-0962].
25. Bellan M, Guzzaloni G, Rinaldi M, Merlotti E, Ferrari C, Tagliaferri A, Pirisi M, Aimaretti G, Scacchi M, Marzullo P. Altered glucose metabolism rather than naive type 2 diabetes mellitus (T2DM) is related to vitamin D status in severe obesity. Cardiovasc Diabetol 2014; 13: 57 [PMID: 24618074 DOI: 10.1186/1475-2840-13-57].
26. Afzal S, Brøndum-Jacobsen P, Bojesen SE, Nordestgaard BG. Vitamin D concentration, obesity, and risk of diabetes: a mendelian randomisation study. Lancet Diabetes Endocrinol 2014; 2: 298-306 [PMID: 24703048 DOI: 10.1016/S2213-8587(13)70200-6].
27. Boland RL. VDR activation of intracellular signaling pathways in skeletal muscle. Mol Cell Endocrinol 2011; 347: 11-16 [PMID: 21664245 DOI: 10.1016/j.mce.2011.05.021].
28. Huhtakangas JA, Olivera CJ, Bishop JE, Zanello LP, Norman AW. The vitamin D receptor is present in caveolae-enriched plasma membranes and binds 1 alpha,25(OH)2-vitamin D3 in vivo and in vitro. Mol Endocrinol 2004; 18: 2660-2671 [PMID: 15272054].
29. Holick MF, Garabedian M. Vitamin D: photobiology, metabolism, mechanism of action, and clinical applications. In: Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. Washington, DC: American Society for Bone and Mineral Research, 2006: 129-137.
30. Bland R, Walker EA, Hughes SV, Stewart PM, Hewison M. Constitutive expression of 25-hydroxyvitamin D3-1alphahydroxylase in a transformed human proximal tubule cell line: evidence for direct regulation of vitamin D metabolism by calcium. Endocrinology 1999; 140: 2027-2034 [PMID: 10218951].
31. Bai XY, Miao D, Goltzman D, Karaplis AC. The autosomal dominant hypophosphatemic rickets R176Q mutation in fibroblast growth factor 23 resists proteolytic cleavage and enhances in vivo biological potency. J Biol Chem 2003; 278: 9843-9849 [PMID: 12519781].
32. Stoffels K, Overbergh L, Giulietti A, Verlinden L, Bouillon R, Mathieu C. Immune regulation of 25-hydroxyvitamin-D3-1alpha-hydroxylase in human monocytes. J Bone Miner Res 2006; 21: 37-47 [PMID: 16355272].
33. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006; 311: 1770-1773 [PMID: 16497887].
34. Chen KS, DeLuca HF. Cloning of the human 1 alpha,25-dihydroxyvitamin D-3 24-hydroxylase gene promoter and identification of two vitamin D-responsive elements. Biochim Biophys Acta 1995; 1263: 1-9 [PMID: 7632726].
35. Wu S, Finch J, Zhong M, Slatopolsky E, Grieff M, Brown AJ. Expression of the renal 25-hydroxyvitamin D-24-hydroxylase gene: regulation by dietary phosphate. Am J Physiol 1996; 271: F203-F208 [PMID: 8760262].
36. Bouillon R, Van Assche FA, Van Baelen H, Heyns W, De Moor P. Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration. J Clin Invest 1981; 67: 589-596 [PMID: 6894152].
37. Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr 2012; 95: 91-100 [PMID: 22170374 DOI: 103945/ajcn.111.014779].
38. Pilz S, Tomaschitz A, März W, Drechsler C, Ritz E, Zittermann A, Cavalier E, Pieber TR, Lappe JM, Grant WB, Holick MF, Dekker JM. Vitamin D, cardiovascular disease and mortality. Clin Endocrinol (Oxf) 2011; 75: 575-584 [PMID: 21682758 DOI: 10.1111/j.1365-2265.2011].
39. Trépo E, Ouziel R, Pradat P, Momozawa Y, Quertinmont E, Gervy C, Gustot T, Degré D, Vercruysse V, Deltenre P, Verset L, Gulbis B, Franchimont D, Devière J, Lemmers A, Moreno C. Marked 25-hydroxyvitamin D deficiency is associated with poor prognosis in patients with alcoholic liver disease. J Hepatol 2013; 59: 344-350 [PMID: 23557869 DOI: 101016/j.jhep.2013.03.024].
40. Putz-Bankuti C, Pilz S, Stojakovic T, Scharnagl H, Pieber TR, Trauner M, Obermayer-Pietsch B, Stauber RE. Association of 25-hydroxyvitamin D levels with liver dysfunction and mortality in chronic liver disease. Liver Int 2012; 32: 845-851 [PMID: 22222013 DOI: 10.1111/j.1478-3231.2011.02735.x].
41. Malham M, Jørgensen SP, Ott P, Agnholt J, Vilstrup H, Borre M, Dahlerup JF. Vitamin D deficiency in cirrhosis relates to liver dysfunction rather than aetiology. World J Gastroenterol 2011; 17: 922-925 [PMID: 21412501 DOI: 10.3748/wjg.v17.i7.922].
42. Anty R, Tonohouan M, Ferrari-Panaia P, Piche T, Pariente A, Anstee QM, Gual P, Tran A. Low Levels of 25-Hydroxy Vitamin D are Independently Associated with the Risk of Bacterial Infection in Cirrhotic Patients. Clin Transl Gastroenterol 2014; 5: e56 [PMID: 24871371 DOI: 10.1038/ctg.2014.6].
43. Targher G, Bertolini L, Scala L, Cigolini M, Zenari L, Falezza G, Arcaro G. Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 2007; 17: 517-524 [PMID: 16928437].
44. Barchetta I, Carotti S, Labbadia G, Gentilucci UV, Muda AO, Angelico F, Silecchia G, Leonetti F, Fraioli A, Picardi A, Morini S, Cavallo MG. Liver vitamin D receptor, CYP2R1, and CYP27A1 expression: relationship with liver histology and vitamin D3 levels in patients with nonalcoholic steatohepatitis or hepatitis C virus. Hepatology 2012; 56: 2180-2187 [PMID: 22753133 DOI: 10.1002/hep.25930].
45. Skinner RK, Sherlock S, Long RG, Wilis MR. 25-Hydroxylation of vitamin D in primary biliary cirrhosis. Lancet 1977; 1: 720-721 [PMID: 66518].
46. Compston JE. Hepatic osteodystrophy: vitamin D metabolism in patients with liver disease. Gut 1986; 27: 1073-1090 [PMID: 3530896].
47. Masuda S, Okano T, Osawa K, Shinjo M, Suematsu T, Kobayashi T. Concentrations of vitamin D-binding protein and vitamin D metabolites in plasma of patients with liver cirrhosis. J Nutr Sci Vitaminol (Tokyo) 1989; 35: 225-234 [PMID: 2585144].
48. White P, Cooke N. The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab 2000; 11: 320-327 [PMID: 10996527].
49. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2014; 2: 76-89 [PMID: 24622671 DOI: 10.1016/S2213-8587(13)70165-7].
50. Petta S, Cammà C, Scazzone C, Tripodo C, Di Marco V, Bono A, Cabibi D, Licata G, Porcasi R, Marchesini G, Craxí A. 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; 51: 1158-1167 [PMID: 20162613 DOI: 10.1002/hep.23489].
51. Adams JS, Hewison M. Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat Clin Pract Endocrinol Metab 2008; 4: 80-90 [PMID: 18212810 DOI: 10.1038/ncpendmet0716].
52. Sadeghi K, Wessner B, Laggner U, Ploder M, Tamandl D, Friedl J, Zügel U, Steinmeyer A, Pollak A, Roth E, Boltz-Nitulescu G, Spittler A. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol 2006; 36 361-370 [PMID: 16402404].
53. Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liver disease. Liver Int 2006; 26: 1175-1186 [PMID: 17105582].
54. Gascon-Barré M, Demers C, Mirshahi A, Néron S, Zalzal S, Nanci A. The normal liver harbors the vitamin D nuclear receptor in nonparenchymal and biliary epithelial cells. Hepatology 2003; 37: 1034-1042 [PMID: 12717384].
55. D'Aldebert E, Biyeyeme Bi Mve MJ, Mergey M, Wendum D, Firrincieli D, Coilly A, Fouassier L, Corpechot C, Poupon R, Housset C, Chignard N. Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium. Gastroenterology 2009; 136: 1435-1443 [PMID: 19245866 DOI: 10.1053/j.gastro.2008.12.040].
56. Han S, Li T, Ellis E, Strom S, Chiang JY. A novel bile acid-activated vitamin D receptor signaling in human hepatocytes. Mol Endocrinol 2010; 24: 1151-1164 [PMID: 20371703 DOI: 101210/me.2009-0482].
57. Schmidt DR, Holmstrom SR, Fon Tacer K, Bookout AL, Kliewer SA, Mangelsdorf DJ. Regulation of bile acid synthesis by fat-soluble vitamins A and D. J Biol Chem 2010; 285: 14486-14494 [PMID: 20233723 DOI: 10.1074/jbc.M110.116004].
58. Khan AA, Chow EC, van Loenen-Weemaes AM, Porte RJ, Pang KS, Groothuis GM. Comparison of effects of VDR versus PXR, FXR and GR ligands on the regulation of CYP3A isozymes in rat and human intestine and liver. Eur J Pharm Sci 2009; 37: 115-125 [PMID: 19429418 DOI: 10.1016/j.ejps.2009.01.006].
59. Shea MK, Benjamin EJ, Dupuis J, Massaro JM, Jacques PF, D' Agostino RB, Ordovas JM, O'Donnell CJ, Dawson-Hughes B, Vasan RS, Booth SL. Genetic and non-genetic correlates of vitamins K and D. Eur J Clin Nutr 2009; 63: 458-464 [PMID: 18030310].
60. Hunter D, De Lange M, Snieder H, MacGregor AJ, Swaminathan R, Thakker RV, Spector TD. Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. J Bone Miner Res 2001; 16: 371-378 [PMID: 11204437].
61. Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, Kiel DP, Streeten EA, Ohlsson C, Koller DL, Peltonen L, Cooper JD, O'Reilly PF, Houston DK, Glazer NL, Vandenput L, Peacock M, Shi J, Rivadeneira F, McCarthy MI, Anneli P, de Boer IH, Mangino M, Kato B, Smyth DJ, Booth SL, Jacques PF, Burke GL, Goodarzi M, Cheung CL, Wolf M, Rice K, Goltzman D, Hidiroglou N, Ladouceur M, Wareham NJ, Hocking LJ, Hart D, Arden NK, Cooper C, Malik S, Fraser WD, Hartikainen AL, Zhai G, Macdonald HM, Forouhi NG, Loos RJ, Reid DM, Hakim A, Dennison E, Liu Y, Power C, Stevens HE, Jaana L, Vasan RS, Soranzo N, Bojunga J, Psaty BM, Lorentzon M, Foroud T, Harris TB, Hofman A, Jansson JO, Cauley JA, Uitterlinden AG, Gibson Q, Järvelin MR, Karasik D, Siscovick DS, Econs MJ, Kritchevsky SB, Florez JC, Todd JA, Dupuis J, Hyppönen E, Spector TD. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 2010; 376: 180-188 [PMID: 20541252 DOI: 10.1016/S0140-6736(10)60588-0].
62. Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, Mc-Cullough ML, Gallicchio L, Jacobs EJ, Ascherio A, Helzlsouer K, Jacobs KB, Li Q, Weinstein SJ, Purdue M, Virtamo J, Horst R, Wheeler W, Chanock S, Hunter DJ, Hayes RB, Kraft P, Albanes D. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 2010; 19: 2739-2745 [PMID: 20418485 DOI: 10.1093/hmg/ddq155].
63. Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med 2013; 369: 1991-2000 [PMID: 24256378 DOI: 10.1056/NEJMoa1306357].
64. Tanaka A, Nezu S, Uegaki S, Kikuchi K, Shibuya A, Miyakawa H, Takahashi S, Bianchi I, Zermiani P, Podda M, Ohira H, Invernizzi P, Takikawa H. Vitamin D receptor polymorphisms are associated with increased susceptibility to primary biliary cirrhosis in Japanese and Italian populations. J Hepatol 2009; 50: 1202-1209 [PMID: 19376604 DOI: 101016/j.jhep.2009.01.015].
65. Fan L, Tu X, Zhu Y, Zhou L, Pfeiffer T, Feltens R, Stoecker W, Zhong R. Genetic association of vitamin D receptor polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese. J Gastroenterol Hepatol 2005; 20: 249-255 [PMID: 15683428].
66. Vogel A, Strassburg CP, Manns MP. Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis. Hepatology 2002; 35: 126-131 [PMID: 11786968].
67. Halmos B, Szalay F, Cserniczky T, Nemesanszky E, Lakatos P, Barlage S, Schmitz G, Romics L, Csaszar A. Association of primary biliary cirrhosis with vitamin D receptor BsmI genotype polymorphism in a Hungarian population. Dig Dis Sci 2000; 45: 1091-1095 [PMID: 10877221].
68. Baur K, Mertens JC, Schmitt J, Iwata R, Stieger B, Eloranta JJ, Frei P, Stickel F, Dill MT, Seifert B, Ferrari HA, von Eckardstein A, Bochud PY, Müllhaupt B, Geier A. 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; 32: 635-643 [PMID: 22151003 DOI: 101111/j.1478-3231.2011.02674].
69. Falleti E, Bitetto D, Fabris C, Cussigh A, Fontanini E, Fornasiere E, Fumolo E, Bignulin S, Cmet S, Minisini R, Pirisi M, Toniutto P. Vitamin D receptor gene polymorphisms and hepatocellular carcinoma in alcoholic cirrhosis. World J Gastroenterol 2010; 16: 3016-3024 [PMID: 20572305].
70. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 2007; 167: 1730-1737 [PMID: 17846391].
71. Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol 2014; 810: 500-525 [PMID: 25207384].
72. Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC, Khan H, Baena CP, Prabhakaran D, Hoshen MB, Feldman BS, Pan A, Johnson L, Crowe F, Hu FB, Franco OH. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ 2014; 348: g1903 [PMID: 24690623 DOI: 10.1136/bmj.g1903].
73. The National Academies Collection: Reports funded by National Institutes of Health; Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. The National Academies Collection: Reports funded by National Institutes of Health. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US), 2011 [PMID: 21796828].
74. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 1911-1930 [PMID: 21646368].
75. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol 2009; 51: 237-267 [PMID: 19501929 DOI: 101016/j.jhep.2009.04.009].
76. Corey RL, Whitaker MD, Crowell MD, Keddis MT, Aqel B, Balan V, Byrne T, Carey E, Douglas DD, Harrison ME, Vargas HE, Rakela J. Vitamin D deficiency, parathyroid hormone levels, and bone disease among patients with endstage liver disease and normal serum creatinine awaiting liver transplantation. Clin Transplant 2014; 28: 579-584 [PMID: 24628047 DOI: 10.1111/ctr.12351].
77. Chen CC, Wang SS, Jeng FS, Lee SD. Metabolic bone disease of liver cirrhosis: is it parallel to the clinical severity of cirrhosis? J Gastroenterol Hepatol 1996; 11: 417-421 [PMID: 8743912].
78. Terán A, Fábrega E, Moraleja I, Iruzubieta P, García-Inzueta MT, Crespo J, Amado JA, Pons-Romero F. Eje calcio-vitamina D-PTH en la cirrosis hepática. Existe un hipoparatiroidismo relativo en el paciente cirrótico? Gatroenterol Hepatol 2013; 36 (Congres 1): 83-84.
79. Bikle DD, Halloran BP, Gee E, Ryzen E, Haddad JG. Free 25-hydroxyvitamin D levels are normal in subjects with liver disease and reduced total 25-hydroxyvitamin D levels. J Clin Invest 1986; 78: 748-752 [PMID: 3745436].
80. Nakchbandi IA, van der Merwe SW. Current understanding of osteoporosis associated with liver disease. Nat Rev Gastroenterol Hepatol 2009; 6: 660-670 [PMID: 19881518 DOI: 101038/nrgastro.2009.166].
81. Axmann R, Böhm C, Krönke G, Zwerina J, Smolen J, Schett G. Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo. Arthritis Rheum 2009; 60: 2747-2756 [PMID: 19714627 DOI: 10.1002/art.24781].
82. Fábrega E, Orive A, García-Suarez C, García-Unzueta M, Antonio Amado J, Pons-Romero F. Osteoprotegerin and RANKL in alcoholic liver cirrhosis. Liver Int 2005; 25: 305-310 [PMID: 15780054].
83. Karan MA, Erten N, Tascioglu C, Karan A, Sindel D, Dilsen G. Osteodystrophy in posthepatitic cirrhosis. Yonsei Med J 2001; 42: 547-552 [PMID: 11675684].
84. Janes CH, Dickson ER, Okazaki R, Bonde S, McDonagh AF, Riggs BL. Role of hyperbilirubinemia in the impairment of osteoblast proliferation associated with cholestatic jaundice. J Clin Invest 1995; 95: 2581-2586 [PMID: 7769100].
85. Mitra R. Adverse effects of corticosteroids on bone metabolism: a review. PM R 2011; 3: 466-471; quiz 471 [PMID: 21570035].
86. Liu L, Chen M, Hankins SR, Nùñez AE, Watson RA, Weinstock PJ, Newschaffer CJ, Eisen HJ. Serum 25-hydroxyvitamin D concentration and mortality from heart failure and cardiovascular disease, and premature mortality from allcause in United States adults. Am J Cardiol 2012; 110: 834-839 [PMID: 22658246 DOI: 10.1016/j.amjcard.2012.05.013].
87. Li YC, Qiao G, Uskokovic M, Xiang W, Zheng W, Kong J. Vitamin D: a negative endocrine regulator of the reninangiotensin system and blood pressure. J Steroid Biochem Mol Biol 2004; 89-90: 387-392 [PMID: 15225806].
88. Cai Q, Tapper DN, Gilmour RF, deTalamoni N, Aloia RC, Wasserman RH. Modulation of the excitability of avian peripheral nerves by vitamin D: relation to calbindin-D28k, calcium status and lipid composition. Cell Calcium 1994; 15: 401-410 [PMID: 8033198].
89. 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 USA 1996; 93: 7861-7864 [PMID: 8755567].
90. Elias J, Marian B, Edling C, Lachmann B, Noe CR, Rolf SH, Schuster I. Induction of apoptosis by vitamin D metabolites and analogs in a glioma cell line. Recent Results Cancer Res 2003; 164: 319-332 [PMID: 12899531].
91. Valrance ME, Welsh J. Breast cancer cell regulation by highdose Vitamin D compounds in the absence of nuclear vitamin D receptor. J Steroid Biochem Mol Biol 2004; 89-90: 221-225 [PMID: 15225775].
92. Abramovitch S, Dahan-Bachar L, Sharvit E, Weisman Y, Ben Tov A, Brazowski E, Reif S. Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats. Gut 2011; 60: 1728-1737 [PMID: 21816960 DOI: 10.1136/gut.2010.234666].
93. Neeman R, Abramovitch S, Sharvit E, Elad-Sfadia G, Haklai R, Kloog Y, Reif S. Vitamin D and S-farnesylthiosalicylic acid have a synergistic effect on hepatic stellate cells proliferation. Dig Dis Sci 2014; 59: 2462-2469 [PMID: 24942325].
94. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune system. Curr Opin Pharmacol 2010; 10: 482-496 [PMID: 20427238].
95. Gombart AF. The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol 2009; 4: 1151-1165 [PMID: 19895218 DOI: 10.2217/fmb.09.87].
96. Murillo G, Nagpal V, Tiwari N, Benya RV, Mehta RG. Actions of vitamin D are mediated by the TLR4 pathway in inflammation-induced colon cancer. J Steroid Biochem Mol Biol 2010; 121: 403-407 [PMID: 20214986 DOI: 10.1016/j.jsbmb.2010.03.009].
97. Dickie LJ, Church LD, Coulthard LR, Mathews RJ, Emery P, McDermott MF. Vitamin D3 down-regulates intracellular Toll-like receptor 9 expression and Toll-like receptor 9-induced IL-6 production in human monocytes. Rheumatology (Oxford) 2010; 49: 1466-1471 [PMID: 20435648].
98. Mencin A, Kluwe J, Schwabe RF. Toll-like receptors as targets in chronic liver diseases. Gut 2009; 58: 704-720 [PMID: 19359436].
99. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007; 56: 1761-1772 [PMID: 17456850].
100. Parlesak A, Schäfer C, Schütz T, Bode JC, Bode C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. J Hepatol 2000; 32: 742-747 [PMID: 10845660].
101. Guo J, Friedman SL. Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis. Fibrogenesis Tissue Repair 2010;3: 21 [PMID: 20964825 DOI: 10.1186/1755-1536-3-21].
102. Holt PR, Arber N, Halmos B, Forde K, Kissileff H, McGlynn KA, Moss SF, Kurihara N, Fan K, Yang K, Lipkin M. Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D. Cancer Epidemiol Biomarkers Prev 2002; 11: 113-119 [PMID: 11815408].
103. Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, Bissonnette M, Li YC. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol 2008; 294: G208-G216 [PMID: 17962355].
104. Kitson MT, Roberts SK. D-livering the message: the importance of vitamin D status in chronic liver disease. J Hepatol 2012; 57 897-909 [PMID: 22634121 DOI: 10.1016/j.jhep.2012.04.033].
105. von Essen MR, 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: 344-349 [PMID: 20208539 DOI: 10.1038/ni.1851].
106. Lemire JM, Archer DC, Beck L, Spiegelberg HL. Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. J Nutr 1995; 125: 1704S-1708S [PMID: 7782931].
107. Penna G, Adorini L. 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 2000; 164: 2405-2411 [PMID: 10679076].
108. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O' Garra A. 1alpha, 25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 2001; 167: 4974-4980 [PMID: 11673504].
109. Daniel C, Sartory NA, Zahn N, Radeke HH, Stein JM. Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther 2008; 324: 23-33 [PMID: 17911375].
110. Penna G, Roncari A, Amuchastegui S, Daniel KC, Berti E, Colonna M, Adorini L. Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1,25-dihydroxyvitamin D3. Blood 2005; 106: 3490-3497 [PMID: 16030186].
111. Ding N, Yu RT, Subramaniam N, Sherman MH, Wilson C, Rao R, Leblanc M, Coulter S, He M, Scott C, Lau SL, Atkins AR, Barish GD, Gunton JE, Liddle C, Downes M, Evans RM. A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response. Cell 2013; 153: 601-613 [PMID: 23622244 DOI: 10.1016/j.cell.2013.03.028].
112. Abramovitch S, Sharvit E, Weisman Y, Bentov A, Brazowski E, Cohen G, Volovelsky O, Reif S. Vitamin D inhibits development of liver fibrosis in animal model but cannot ameliorate established cirrhosis. Am J Physiol Gastrointest Liver Physiol 2014; Epub ahead of print [PMID: 25214398].
113. Beard JA, Bearden A, Striker R. Vitamin D and the anti-viral state. J Clin Virol 2011; 50: 194-200 [PMID: 21242105 DOI: 101016/j.jcv.2010.12.006].
114. World Health Organization. Fact sheet No 164. [updated 2014 April]. Available from: URL: http://www.who.int/mediacentre/factsheets/fs164/en/.
115. Lange CM, Bojunga J, Ramos-Lopez E, von Wagner M, Hassler A, Vermehren J, Herrmann E, Badenhoop K, Zeuzem S, Sarrazin C. 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: 887-893 [PMID: 21145801 DOI: 10.1016/j.jhep.2010.08.036].
116. Lange CM, Bibert S, Kutalik Z, Burgisser P, Cerny A, Dufour JF, Geier A, Gerlach TJ, Heim MH, Malinverni R, Negro F, Regenass S, Badenhoop K, Bojunga J, Sarrazin C, Zeuzem S, Müller T, Berg T, Bochud PY, Moradpour D. A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C. PLoS One 2012; 7: e40159 [PMID: 22808108].
117. Choudhary NS, Tomar M, Chawla YK, Bhadada SK, Khandelwal N, Dhiman RK, Duseja A, Bhansali A. Hepatic osteodystrophy is common in patients with noncholestatic liver disease. Dig Dis Sci 2011; 56: 3323-3327 [PMID: 21573732 DOI: 10.1007/s10620-011-1722-y].
118. Ramos-Lopez E, Kahles H, Weber S, Kukic A, Penna-Martinez M, Badenhoop K, Louwen F. Gestational diabetes mellitus and vitamin D deficiency: genetic contribution of CYP27B1 and CYP2R1 polymorphisms. Diabetes Obes Metab 2008; 10: 683-685 [PMID: 18476984 DOI: 10.1111/j.1463-1326.2008.00879.x].
119. Bellecave P, Sarasin-Filipowicz M, Donzé O, Kennel A, Gouttenoire J, Meylan E, Terracciano L, Tschopp J, Sarrazin C, Berg T, Moradpour D, Heim MH. Cleavage of mitochondrial antiviral signaling protein in the liver of patients with chronic hepatitis C correlates with a reduced activation of the endogenous interferon system. Hepatology 2010; 51: 1127-1136 [PMID: 20044805 DOI: 10.1002/hep.23426].
120. Clark PJ, Thompson AJ, Vock DM, Kratz LE, Tolun AA, Muir AJ, McHutchison JG, Subramanian M, Millington DM, Kelley RI, Patel K. Hepatitis C virus selectively perturbs the distal cholesterol synthesis pathway in a genotype-specific manner. Hepatology 2012; 56: 49-56 [PMID: 22318926 DOI: 101002/hep.25631].
121. Bitetto D, Fabris C, Fornasiere E, Pipan C, Fumolo E, Cussigh A, Bignulin S, Cmet S, Fontanini E, Falleti E, Martinella R, Pirisi M, Toniutto P. Vitamin D supplementation improves response to antiviral treatment for recurrent hepatitis C. Transpl Int 2011; 24: 43-50 [PMID: 20649944 DOI: 10.1111/j.1432-2277.2010.01141.x].
122. Nimer A, Mouch A. Vitamin D improves viral response in hepatitis C genotype 2-3 naïve patients. World J Gastroenterol 2012; 18: 800-805 [PMID: 22371640 DOI: 10.3748/wjg.v18.i8.800].
123. Abu-Mouch S, Fireman Z, Jarchovsky J, Zeina AR, Assy N. Vitamin D supplementation improves sustained virologic response in chronic hepatitis C (genotype 1)-naïve patients. World J Gastroenterol 2011; 17: 5184-5190 [PMID: 22215943 DOI: 10.3748/wjg.v17.i47.5184].
124. Ng TI, Mo H, Pilot-Matias T, He Y, Koev G, Krishnan P, Mondal R, Pithawalla R, He W, Dekhtyar T, Packer J, Schurdak M, Molla A. Identification of host genes involved in hepatitis C virus replication by small interfering RNA technology. Hepatology 2007; 45: 1413-1421 [PMID: 17518369].
125. Shirakawa H, Matsumoto A, Joshita S, Komatsu M, Tanaka N, Umemura T, Ichijo T, Yoshizawa K, Kiyosawa K, Tanaka E. Pretreatment prediction of virological response to peginterferon plus ribavirin therapy in chronic hepatitis C patients using viral and host factors. Hepatology 2008; 48: 1753-1760 [PMID: 18925643 DOI: 10.1002/hep.22543].
126. Yano M, Ikeda M, Abe K, Dansako H, Ohkoshi S, Aoyagi Y, Kato N. Comprehensive analysis of the effects of ordinary nutrients on hepatitis C virus RNA replication in cell culture. Antimicrob Agents Chemother 2007; 51: 2016-2027 [PMID: 17420205].
127. Gal-Tanamy M, Bachmetov L, Ravid A, Koren R, Erman A, Tur-Kaspa R, Zemel R. Vitamin D: an innate antiviral agent suppressing hepatitis C virus in human hepatocytes. Hepatology 2011; 54: 1570-1579 [PMID: 21793032 DOI: 10.1002/hep.24575].
128. Matsumura T, Kato T, Sugiyama N, Tasaka-Fujita M, Murayama A, Masaki T, Wakita T, Imawari M. 25-Hydroxyvitamin D3 suppresses hepatitis C virus production. Hepatology 2012; 56: 1231-1239 [PMID: 22487892 DOI: 10.1002/hep.25763].
129. Falleti E, Cmet S, Fabris C, Fattovich G, Cussigh A, Bitetto D, Ceriani E, Lenisa I, Dissegna D, Ieluzzi D, Rostello A, Pirisi M, Toniutto P. Genetic polymorphisms of vitamin D pathway predict antiviral treatment outcome in slow responder naïve patients with chronic hepatitis C. PLoS One 2013; 8: e80764 [PMID: 24244713 DOI: 10.1371/journal.pone.0080764].
130. García-álvarez M, Pineda-Tenor D, Jiménez-Sousa MA, Fernández-Rodríguez A, Guzmán-Fulgencio M, Resino S. Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: A meta-analysis. Hepatology 2014; 60: 1541-1550 [PMID: 24975775 DOI: 10.1002/hep.27281].
131. Terrier B, Carrat F, Geri G, Pol S, Piroth L, Halfon P, Poynard T, Souberbielle JC, Cacoub P. Low 25-OH vitamin D serum levels correlate with severe fibrosis in HIV-HCV coinfected patients with chronic hepatitis. J Hepatol 2011; 55: 756-761 [PMID: 21334402 DOI: 10.1016/j.jhep.2011.01.041].
132. Petta S, Grimaudo S, Marco VD, Scazzone C, Macaluso FS, Cammà C, Cabibi D, Pipitone R, Craxì A. Association of vitamin D serum levels and its common genetic determinants, with severity of liver fibrosis in genotype 1 chronic hepatitis C patients. J Viral Hepat 2013; 20: 486-493 [PMID: 23730842 DOI: 10.1111/jvh.12072].
133. Nseir W, Gali M, Mouch SA, Djibre A, Nassar F, Assy N. Baseline serum HDL and vitamin D levels are strongly associated with SVR in chronic hepatitis C naïve genotype 1 patients. J Hepatol 2011; 54 Suppl 1: S450 [DOI: 10.1016/S0168-8278(11)61140-9].
134. Jazwinski A, Clark PJ, Tillmann HL, Muir AJ. Vitamin D and treatment response in African American patients with HCV genotype 1. Hepatology 2011; 54 Suppl S1: 853.
135. Weintraub SJ, Fleckenstein JF, Marion TN, Madey MA, Mahmoudi TM, Schechtman KB. Vitamin D and the racial difference in the genotype 1 chronic hepatitis C treatment response. Am J Clin Nutr 2012; 96: 1025-1031 [PMID: 23015322 DOI: 10.3945/ajcn.112.039974].
136. Bitetto D, Fattovich G, Fabris C, Ceriani E, Falleti E, Fornasiere E, Pasino M, Ieluzzi D, Cussigh A, Cmet S, Pirisi M, Toniutto P. 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: 1118-1126 [PMID: 21480318 DOI: 10.1002/hep.24201].
137. Kitson MT, Dore GJ, George J, Button P, McCaughan GW, Crawford DH, Sievert W, Weltman MD, Cheng WS, Roberts SK. Vitamin D status does not predict sustained virologic response or fibrosis stage in chronic hepatitis C genotype 1 infection. J Hepatol 2013; 58: 467-472 [PMID: 23183524 DOI: 101016/j.jhep.2012.11.017].
138. Grammatikos G, Lange C, Susser S, Schwendy S, Dikopoulos N, Buggisch P, Encke J, Teuber G, Goeser T, Thimme R, Klinker H, Boecher WO, Schulte-Frohlinde E, Penna-Martinez M, Badenhoop K, Zeuzem S, Berg T, Sarrazin C. Vitamin D levels vary during antiviral treatment but are unable to predict treatment outcome in HCV genotype 1 infected patients. PLoS One 2014; 9: e87974 [PMID: 24516573 DOI: 10.1371/journal.pone.0087974].
139. Corey KE, Zheng H, Mendez-Navarro J, Delgado-Borrego A, Dienstag JL, Chung RT. Serum vitamin D levels are not predictive of the progression of chronic liver disease in hepatitis C patients with advanced fibrosis. PLoS One 2012; 7: e27144 [PMID: 22359532 DOI: 10.1371/journal.pone.0027144].
140. Esmat G, El Raziky M, Elsharkawy A, Sabry D, Hassany M, Ahmed A, Assem N, El Kassas M, Doss W. Impact of Vitamin D Supplementation on Sustained Virological Response in Chronic Hepatitis C Genotype 4 Patients Treated by Pegylated Interferon/Ribavirin. J Interferon Cytokine Res 2014; Epub ahead of print [PMID: 25061714].
141. Kitson MT, Sarrazin C, Toniutto P, Eslick GD, Roberts SK. Vitamin D level and sustained virologic response to interferon-based antiviral therapy in chronic hepatitis C: A systematic review and meta-analysis. J Hepatol 2014; 61: 1247-1252 [PMID: 25135863 DOI: 10.1016/j.jhep.2014.08.004].
142. Yokoyama S, Takahashi S, Kawakami Y, Hayes CN, Kohno H, Kohno H, Tsuji K, Aisaka Y, Kira S, Yamashina K, Nonaka M, Moriya T, Kitamoto M, Aimitsu S, Nakanishi T, Kawakami H, Chayama K. Effect of vitamin D supplementation on pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b: a randomized controlled trial. J Viral Hepat 2014; 21: 348-356 [PMID: 24716637 DOI: 10.1111/jvh.12146].
143. Bailey R, Cooper JD, Zeitels L, Smyth DJ, Yang JH, Walker NM, Hyppönen E, Dunger DB, Ramos-Lopez E, Badenhoop K, Nejentsev S, Todd JA. Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes 2007; 56 2616-2621 [PMID: 17606874].
144. Alvarez JA, Ashraf A. Role of vitamin d in insulin secretion and insulin sensitivity for glucose homeostasis. Int J Endocrinol 2010; 2010: 351385 [PMID: 20011094 DOI: 10.1155/2010/351385].
145. Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract 2003; 57: 258-261 [PMID: 12800453].
146. Grasso A, Malfatti F, De Leo P, Martines H, Fabris P, Toscanini F, Anselmo M, Menardo G. Insulin resistance predicts rapid virological response in non-diabetic, non-cirrhotic genotype 1 HCV patients treated with peginterferon alpha-2b plus ribavirin. J Hepatol 2009; 51: 984-990 [PMID: 19695729 DOI: 10.1016/j.jhep.2009.07.008].
147. Resnick LM. Calcium metabolism in hypertension and allied metabolic disorders. Diabetes Care 1991; 14: 505-520 [PMID: 1864222].
148. Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006; 43: S99-S112 [PMID: 16447287].
149. Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 2007; 11: 1-16, vii [PMID: 17544968].
150. Argo CK, Caldwell SH. Epidemiology and natural history of non-alcoholic steatohepatitis. Clin Liver Dis 2009; 13: 511-531 [PMID: 19818302 DOI: 10.1016/j.cld.2009.07.005].
151. Lim JS, Mietus-Snyder M, Valente A, Schwarz JM, Lustig RH. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat Rev Gastroenterol Hepatol 2010; 7: 251-264 [PMID: 20368739 DOI: 10.1038/nrgastro.2010.41].
152. Kraegen EW, Cooney GJ. Free fatty acids and skeletal muscle insulin resistance. Curr Opin Lipidol 2008; 19: 235-241 [PMID: 18460913 DOI: 10.1097/01.mol.0000319118.44995.9a].
153. Ford ES, Ajani UA, McGuire LC, Liu S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care 2005; 28: 1228-1230 [PMID: 15855599].
154. Stein EM, Strain G, Sinha N, Ortiz D, Pomp A, Dakin G, McMahon DJ, Bockman R, Silverberg SJ. Vitamin D insufficiency prior to bariatric surgery: risk factors and a pilot treatment study. Clin Endocrinol (Oxf) 2009; 71: 176-183 [PMID: 19018785 DOI: 10.1111/j.1365-2265.2008.03470.x].
155. Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL, Jacques PF. Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. J Nutr 2009; 139: 329-334 [PMID: 19106328 DOI: 10.3945/jn.108.093831].
156. McCarty MF. Secondary hyperparathyroidism promotes the acute phase response-a rationale for supplemental vitamin D in prevention of vascular events in the elderly. Med Hypotheses 2005; 64: 1022-1026 [PMID: 15780504].
157. Nagpal J, Pande JN, Bhartia A. A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. Diabet Med 2009; 26: 19-27 [PMID: 19125756 DOI: 10.1111/j.1464-5491.2008.02636.x].
158. von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient-a randomised, placebo-controlled trial. Br J Nutr 2010; 103: 549-555 [PMID: 19781131 DOI: 10.1017/S0007114509992017].
159. Inomata S, Kadowaki S, Yamatani T, Fukase M, Fujita T. Effect of 1 alpha (OH)-vitamin D3 on insulin secretion in diabetes mellitus. Bone Miner 1986; 1: 187-192 [PMID: 3334207].
160. Palomer X, González-Clemente JM, Blanco-Vaca F, Mauricio D. Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab 2008; 10: 185-197 [PMID: 18269634 DOI: 10.1111/j.1463-1326.2007.00710.x].
161. Mak RH, Wong JH. The vitamin D/parathyroid hormone axis in the pathogenesis of hypertension and insulin resistance in uremia. Miner Electrolyte Metab 1992; 18: 156-159 [PMID: 1465050].
162. Hitman GA, Mannan N, McDermott MF, Aganna E, Ogunkolade BW, Hales CN, Boucher BJ. Vitamin D receptor gene polymorphisms influence insulin secretion in Bangladeshi Asians. Diabetes 1998; 47: 688-690 [PMID: 9568705].
163. Zuñiga S, Firrincieli D, Lasnier E, Miquel JF, Housset C, Chignard N. Invalidation of the vitamin D nuclear receptor promotes liver steatosis. Hepatology 2010; 52 Suppl 1: 1058A.
164. Li T, Owsley E, Matozel M, Hsu P, Novak CM, Chiang JY. Transgenic expression of cholesterol 7alpha-hydroxylase in the liver prevents high-fat diet-induced obesity and insulin resistance in mice. Hepatology 2010; 52: 678-690 [PMID: 20623580 DOI: 10.1002/hep.23721].
165. Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 2004; 79: 820-825 [PMID: 15113720].
166. Bourlon PM, Faure-Dussert A, Billaudel B. The de novo synthesis of numerous proteins is decreased during vitamin D3 deficiency and is gradually restored by 1, 25-dihydroxyvitamin D3 repletion in the islets of langerhans of rats. J Endocrinol 1999; 162: 101-109 [PMID: 10396026].
167. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 2007; 92: 2017-2029 [PMID: 17389701].
168. Barchetta I, Angelico F, Del Ben M, Baroni MG, Pozzilli P, Morini S, Cavallo MG. 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 2011; 9: 85 [PMID: 21749681 DOI: 101186/1741-7015-9-85].
169. Jablonski KL, Jovanovich A, Holmen J, Targher G, McFann K, Kendrick J, Chonchol M. Low 25-hydroxyvitamin D level is independently associated with non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 2013; 23: 792-798 [PMID: 23415456 DOI: 10.1016/j.numecd.2012.12.006].
170. Black LJ, Jacoby P, She Ping-Delfos WC, Mori TA, Beilin LJ, Olynyk JK, Ayonrinde OT, Huang RC, Holt PG, Hart PH, Oddy WH, Adams LA. Low serum 25-hydroxyvitamin D concentrations associate with non-alcoholic fatty liver disease in adolescents independent of adiposity. J Gastroenterol Hepatol 2014; 29: 1215-1222 [PMID: 24611991 DOI: 10.1111/jgh.12541].
171. Kasapoglu B, Turkay C, Yalcin KS, Carlioglu A, Sozen M, Koktener A. Low vitamin D levels are associated with increased risk for fatty liver disease among non-obese adults. Clin Med 2013; 13: 576-579 [PMID: 24298105 DOI: 10.7861/clinmedicine.13-6-576].
172. Seo JA, Eun CR, Cho H, Lee SK, Yoo HJ, Kim SG, Choi KM, Baik SH, Choi DS, Yim HJ, Shin C, Kim NH. Low vitamin D status is associated with nonalcoholic Fatty liver disease independent of visceral obesity in Korean adults. PLoS One 2013; 8: e75197 [PMID: 24130687 DOI: 10.1371/journal.pone.0075197].
173. Küçükazman M, Ata N, Dal KA, Yeniova AÖ, Kefeli AE, Basyigit S, Aktas B, Akin KO, A Ladio Lu K, Ure OS, Topal F, Nazligül YA, Beyan E, Ertugrul DT. The association of vitamin D deficiency with non-alcoholic fatty liver disease. Clinics (Sao Paulo) 2014; 69: 542-546 [PMID: 25141113].
174. Yildiz I, Erol OB, Toprak S, Cantez MS, Omer B, Kilic A, Oguz F, Uysalol M, Yekeler E, Unuvar E. Role of vitamin D in children with hepatosteatosis. J Pediatr Gastroenterol Nutr 2014; 59: 106-111 [PMID: 24647335].
175. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000; 72: 690-693 [PMID: 10966885].
176. Yanoff LB, Parikh SJ, Spitalnik A, Denkinger B, Sebring NG, Slaughter P, McHugh T, Remaley AT, Yanovski JA. The prevalence of hypovitaminosis D and secondary hyperparathyroidism in obese Black Americans. Clin Endocrinol (Oxf) 2006; 64: 523-529 [PMID: 16649971].
177. Goldner WS, Stoner JA, Thompson J, Taylor K, Larson L, Erickson J, McBride C. Prevalence of vitamin D insufficiency and deficiency in morbidly obese patients: a comparison with non-obese controls. Obes Surg 2008; 18: 145-150 [PMID: 18175194 DOI: 10.1007/s11695-007-9315-8].
178. Dasarathy J, Periyalwar P, Allampati S, Bhinder V, Hawkins C, Brandt P, Khiyami A, McCullough AJ, Dasarathy S. Hypovitaminosis D is associated with increased whole body fat mass and greater severity of non-alcoholic fatty liver disease. Liver Int 2014; 34: e118-e127 [PMID: 24118743 DOI: 10.1111/liv.12312].
179. Manco M, Ciampalini P, Nobili V. Low levels of 25-hydroxyvitamin D(3) in children with biopsy-proven nonalcoholic fatty liver disease. Hepatology 2010; 51: 2229; author reply 2230 [PMID: 20513013 DOI: 10.1002/hep.23724].
180. Nobili V, Giorgio V, Liccardo D, Bedogni G, Morino G, Alisi A, Cianfarani S. Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease. Eur J Endocrinol 2014; 170: 547-553 [PMID: 24412930 DOI: 101530/EJE-13-0609].
181. Rhee EJ, Kim MK, Park SE, Park CY, Baek KH, Lee WY, Kang MI, Park SW, Kim SW, Oh KW. High serum vitamin D levels reduce the risk for nonalcoholic fatty liver disease in healthy men independent of metabolic syndrome. Endocr J 2013; 60: 743-752 [PMID: 23411507].
182. Yin Y, Yu Z, Xia M, Luo X, Lu X, Ling W. Vitamin D attenuates high fat diet-induced hepatic steatosis in rats by modulating lipid metabolism. Eur J Clin Invest 2012; 42: 1189-1196 [PMID: 22958216 DOI: 10.1111/j.1365-2362.2012.02706.x].
183. Ngo DT, Sverdlov AL, McNeil JJ, Horowitz JD. Does vitamin D modulate asymmetric dimethylarginine and C-reactive protein concentrations? Am J Med 2010; 123: 335-341 [PMID: 20362753].
184. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med 2008; 168: 1340-1349 [PMID: 18574092 DOI: 10.1001/archinte.168.12.134].
185. Day CP. Non-alcoholic fatty liver disease: current concepts and management strategies. Clin Med 2006; 6: 19-25 [PMID: 16521351].
186. Targher G. Non-alcoholic fatty liver disease and cardiovascular disease risk. Curr Cardiovasc Risk Rep 2010; 4: 32-39.
187. Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 2010; 52: 1836-1846 [PMID: 21038418 DOI: 101002/hep.24001].
188. Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med 2000; 343: 1467-1476 [PMID: 11078773].
189. Donato MT, Lahoz A, Jiménez N, Pérez G, Serralta A, Mir J, Castell JV, Gómez-Lechón MJ. Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts. Drug Metab Dispos 2006; 34: 1556-1562 [PMID: 16763015].
190. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2006; 83: 754-759 [PMID: 16600924].
191. Alborzi P, Patel NA, Peterson C, Bills JE, Bekele DM, Bunaye Z, Light RP, Agarwal R. Paricalcitol reduces albuminuria and inflammation in chronic kidney disease: a randomized double-blind pilot trial. Hypertension 2008; 52: 249-255 [PMID: 18606901 DOI: 10.1161/HYPERTENSIONAHA.108.113159].
192. Bucharles S, Barberato SH, Stinghen AE, Gruber B, Piekala L, Dambiski AC, Custodio MR, Pecoits-Filho R. Impact of cholecalciferol treatment on biomarkers of inflammation and myocardial structure in hemodialysis patients without hyperparathyroidism. J Ren Nutr 2012; 22: 284-291 [PMID: 21908203 DOI: 10.1053/j.jrn.2011.07.001].
193. Sharifi N, Amani R, Hajiani E, Cheraghian B. Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial. Endocrine 2014; 47: 70-80 [PMID: 24968737].
194. Timms PM, Mannan N, Hitman GA, Noonan K, Mills PG, Syndercombe-Court D, Aganna E, Price CP, Boucher BJ. Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM 2002; 95: 787-796 [PMID: 12454321].
195. Roth CL, Elfers CT, Figlewicz DP, Melhorn SJ, Morton GJ, Hoofnagle A, Yeh MM, Nelson JE, Kowdley KV. Vitamin D deficiency in obese rats exacerbates nonalcoholic fatty liver disease and increases hepatic resistin and Toll-like receptor activation. Hepatology 2012; 55: 1103-1111 [PMID: 21994008 DOI: 10.1002/hep.24737].
196. Nakano T, Cheng YF, Lai CY, Hsu LW, Chang YC, Deng JY, Huang YZ, Honda H, Chen KD, Wang CC, Chiu KW, Jawan B, Eng HL, Goto S, Chen CL. Impact of artificial sunlight therapy on the progress of non-alcoholic fatty liver disease in rats. J Hepatol 2011; 55: 415-425 [PMID: 21184788 DOI: 101016/j.jhep.2010.11.028].