title: Marked 25-hydroxyvitamin D deficiency is associated with poor prognosis in patients with alcoholic liver disease.
abstract: OBJECTIVE
  Vitamin D deficiency has been frequently reported in advanced liver disease. However, its influence on alcoholic liver disease (ALD) has been poorly elucidated. We investigated the association of vitamin D with clinical, biological, and histological parameters and survival in ALD patients. Furthermore, we explored the effect of vitamin D treatment on ALD patient peripheral blood mononuclear cells (PBMCs), and in a murine experimental model of ALD.
  
  
  METHODS
  Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined in 324 Caucasian ALD patients and 201 healthy controls. In vitro experiments on vitamin D pre-treated PBMCs evaluated TNFα production by ELISA in culture supernatants. Mice were submitted to an ethanol-fed diet and some of them were orally supplemented three times per week with 1,25(OH)2D.
  
  
  RESULTS
  Severe deficiency in 25(OH)D (<10 ng/ml) was significantly associated with higher aspartate aminotransferase levels (p=1.00 × 10(-3)), increased hepatic venous pressure gradient (p=5.80 × 10(-6)), MELD (p=2.50 × 10(-4)), and Child-Pugh scores (p=8.50 × 10(-7)). Furthermore, in multivariable analysis, a low 25(OH)D concentration was associated with cirrhosis (OR=2.13, 95% CI=1.18-3.84, p=0.013) and mortality (HR=4.33, 95% CI=1.47-12.78, p=7.94 × 10(-3)) at one year. In addition, in vitro, 1,25(OH)2D pretreatment decreased TNFα production by stimulated PBMCs of ALD patients (p=3.00 × 10(-3)), while in vivo, it decreased hepatic TNFα expression in ethanol-fed mice (p=0.04).
  
  
  CONCLUSIONS
  Low 25(OH)D levels are associated with increased liver damage and mortality in ALD. Our results suggest that vitamin D might be both a biomarker of severity and a potential therapeutic target in ALD.
authors.affiliation: Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Trépo
authors.forename: Romy
authors.initials: R
authors.lastname: Ouziel
authors.forename: Pierre
authors.initials: P
authors.lastname: Pradat
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Momozawa
authors.forename: Eric
authors.initials: E
authors.lastname: Quertinmont
authors.forename: Christine
authors.initials: C
authors.lastname: Gervy
authors.forename: Thierry
authors.initials: T
authors.lastname: Gustot
authors.forename: Delphine
authors.initials: D
authors.lastname: Degré
authors.forename: Vincent
authors.initials: V
authors.lastname: Vercruysse
authors.forename: Pierre
authors.initials: P
authors.lastname: Deltenre
authors.forename: Laurine
authors.initials: L
authors.lastname: Verset
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gulbis
authors.forename: Denis
authors.initials: D
authors.lastname: Franchimont
authors.forename: Jacques
authors.initials: J
authors.lastname: Devière
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lemmers
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D008108:Liver Diseases, Alcoholic / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications*
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C104450:25-hydroxyvitamin D
keywords: 1,25(OH)(2)D; 1,25-dihydroxyvitamin D; 25(OH)D; 25-hydroxyvitamin D; AC; AH; ALD; ALT; AST; Alcoholic liver disease; BMI; CHC; CI; ConA; Ctrl; ELISA; EtOH; GGT; GWAS; Genetic factors; HCC; HPRT; HR; HRS; HS; HVPG; Inflammation; MELD; NAFLD; OR; PBMCs; RT-PCR; SBP; SNP; TNFα; Vitamin D; alanine aminotransferase; alcoholic cirrhosis; alcoholic hepatitis; alcoholic liver disease; aspartate aminotransferase; body mass index; chronic hepatitis C; concanavalin A; confidence interval; control; enzyme-linked immunosorbent assay; ethanol; gamma-glutamyl transferase; genome-wide association studies; hazards ratio; healthy subjects; hepatic venous pressure gradient; hepatocellular carcinoma; hepatorenal syndrome; hypoxanthine-guanine phosphoribosyltransferase; model for end-stage liver disease; non-alcoholic fatty liver disease; odds ratio; peripheral blood mononuclear cells; reverse transcriptase polymerase chain reaction; single nucleotide polymorphism; spontaneous bacterial peritonitis; tumor necrosis factor-α