title: 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.
abstract: Evidence suggests an association between low serum 25-hydroxy-vitamin D(3) [25(OH)D(3) ] levels and the presence and prognosis of liver disease. Vitamin D receptor (VDR) has been widely detected in the liver, but its expression in the course of liver disease has never been investigated. We evaluated the hepatic expression of VDR along with that of vitamin D 25-hydroxylases in patients with nonalcoholic steatohepatitis (NASH) or chronic hepatitis C (CHC) and its relationship with hepatic histological features and serum 25(OH)D(3) levels. We evaluated 61 patients (25 NASH and 36 CHC) who had undergone liver biopsy for clinical purposes and 20 subjects without liver disease. Serum 25(OH)D(3) was measured via colorimetric assay. Expression of VDR, CYP2R1, and CYP27A1 was evaluated via immunohistochemistry in hepatocytes, cholangiocytes, and liver inflammatory cells. Parenchymal and inflammatory cells from liver biopsies of patients with NASH and CHC expressed VDR, CYP2R1, and CYP27A1. In NASH patients, VDR expression on cholangiocytes was inversely correlated with steatosis severity (P < 0.02), lobular inflammation (P < 0.01), and nonalcoholic fatty liver disease score (P < 0.03). Moreover, expression of CYP2R1 in hepatocytes correlated strongly with VDR positivity on liver inflammatory cells. In CHC subjects, fibrosis stage was associated with low hepatic CYP27A1 expression, whereas portal inflammation was significantly higher in patients with VDR-negative inflammatory cells (P < 0.009) and low VDR expression in hepatocytes (P < 0.03).
  
  
  CONCLUSIONS
  VDR is widely expressed in the liver and inflammatory cells of chronic liver disease patients and its expression is negatively associated with the severity of liver histology in both NASH and CHC patients. These data suggest that vitamin D/VDR system may play a role in the progression of metabolic and viral chronic liver damage. (HEPATOLOGY 2012;56:2180-2187).
authors: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors: Ilaria
authors: I
authors: Barchetta
authors: Simone
authors: S
authors: Carotti
authors: Giancarlo
authors: G
authors: Labbadia
authors: Umberto Vespasiani
authors: UV
authors: Gentilucci
authors: Andrea Onetti
authors: AO
authors: Muda
authors: Francesco
authors: F
authors: Angelico
authors: Gianfranco
authors: G
authors: Silecchia
authors: Frida
authors: F
authors: Leonetti
authors: Antonio
authors: A
authors: Fraioli
authors: Antonio
authors: A
authors: Picardi
authors: Sergio
authors: S
authors: Morini
authors: Maria Gisella
authors: MG
authors: Cavallo
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002112:Calcifediol / Q000097:blood; D053493:Cholestanetriol 26-Monooxygenase / Q000378:metabolism*; D003430:Cross-Sectional Studies; D000072467:Cytochrome P450 Family 2; D005234:Fatty Liver / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D018167:Receptors, Calcitriol / Q000378:metabolism*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D018167:Receptors, Calcitriol; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D002112:Calcifediol