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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
Author(s) -
Barchetta Ilaria,
Carotti Simone,
Labbadia Giancarlo,
Gentilucci Umberto Vespasiani,
Muda Andrea Onetti,
Angelico Francesco,
Silecchia Gianfranco,
Leonetti Frida,
Fraioli Antonio,
Picardi Antonio,
Morini Sergio,
Cavallo Maria Gisella
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.25930
Subject(s) - calcitriol receptor , medicine , vitamin d and neurology , steatosis , steatohepatitis , nonalcoholic fatty liver disease , endocrinology , liver biopsy , liver disease , fatty liver , chronic liver disease , cyp27a1 , biology , biopsy , cirrhosis , bile acid , disease
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). Conclusion: 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. (H EPATOLOGY 2012;56:2180–2187)