title: The hepatic expression of vitamin D receptor is inversely associated with the severity of liver damage in genotype 1 chronic hepatitis C patients.
abstract: OBJECTIVE
  Low 25-hydroxyvitamin D serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC), and experimental evidence suggested a hepatoprotective role of vitamin D via interaction with hepatic vitamin D receptor (VDR). We assessed the hepatic expression of VDR protein and its association with liver disease severity.
  
  
  METHODS
  Ninety-one consecutive patients with biopsy-proven G1CHC and available frozen liver tissue were evaluated. Ten subjects without chronic liver diseases and nine patients with autoimmune hepatitis served as controls. The hepatic expression of VDR protein was assessed by Western blot for quantification and by immunohistochemistry for morphological distribution.
  
  
  RESULTS
  Liver VDR protein was mainly localized in hepatocytes and cholangiocytes, and its expression by a Western blot was similar in chronic hepatitis C (CHC) and controls (1.83 ± 0.97 vs 2.18 ± 0.62, P = .14) but was lower in autoimmune hepatitis (0.84 ± 0.14, P < .001). The expression was lower in CHC with severe necroinflammatory activity (1.44 ± 0.87) vs both controls and CHC with grade 1-2 inflammation (1.94 ± 0.97, P = .01 and P = .03, respectively) but higher compared with autoimmune hepatitis (P = .007). A similar difference was observed in CHC patients with F3-F4 fibrosis whose VDR expression (1.51 ± 1.07) was also lower compared with controls and CHC with F0-F2 fibrosis (1.98 ± 0.89, P = .02 and P = .04, respectively) but higher vs autoimmune hepatitis (P = .003). At multivariate logistic regression analysis, low VDR protein expression remained associated with severe necroinflammatory activity and severe fibrosis (odds ratio 0.543,95% confidence interval 0.288-0.989, P = .04; and odds ratio 0.484,95% confidence interval 0.268-0.877, P = .01, respectively) in CHC after correction for clinical, biochemical, and histological features.
  
  
  CONCLUSIONS
  In a cohort of G1CHC patients, the hepatic expression of VDR protein is associated with the severity of both liver fibrosis and inflammation.
authors.affiliation: Sezione di Gastroenterologia (S.P., S.G., A.D.C., F.S.M., M.G.M., A.C.), Dipartimento Biomedico di Medicina Interna e Specialistica, Cattedra di Anatomia Patologica (C.T., D.C., M.C., C.G.), University of Palermo, 90127 Palermo, Italy; and Dipartimento di Medicina e Gastroenterologia (G.M.), "Alma Mater Studiorum," Università di Bologna, 40126 Bologna, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.forename: Stefania
authors.initials: S
authors.lastname: Grimaudo
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Daniela
authors.initials: D
authors.lastname: Cabibi
authors.forename: Marco
authors.initials: M
authors.lastname: Calvaruso
authors.forename: Antonietta
authors.initials: A
authors.lastname: Di Cristina
authors.forename: Carla
authors.initials: C
authors.lastname: Guarnotta
authors.forename: Fabio Salvatore
authors.initials: FS
authors.lastname: Macaluso
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Minissale
authors.forename: Giulio
authors.initials: G
authors.lastname: Marchesini
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxì
mesh_terms: D000328:Adult; D005260:Female; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D018167:Receptors, Calcitriol