title: Glucocorticoid receptor alpha expression in the intrahepatic biliary epithelium and adjuvant steroid therapy in infants with biliary atresia.
abstract: OBJECTIVE
  In patients with cirrhosis, proinflammatory cytokines increase progressively in relation to the severity of liver dysfunction. Proinflammatory cytokines regulate the expression of glucocorticoid receptors (GcRs). On the other hand, GcRs mediate the effects of glucocorticoid steroids on bile excretion in the biliary epithelium. Glucocorticoid receptors have 2 isoforms: a cytoplasmic glucocorticoid receptor alpha (GcRalpha) mediates their physiological effects, whereas a nuclear localized glucocorticoid receptor beta (GcRbeta) acts as a dominant negative inhibitor of GcRalpha activity. We examined the histology features of liver biopsy and the expression of GcRalpha in the intrahepatic biliary epithelium in infants with biliary atresia.
  
  
  METHODS
  The patients were divided into 2 groups: patients in group 1 (n = 17) had a total bilirubin level below 1.0 mg/dL at least once after surgery, whereas patients in group 2 (n = 14) has never had bilirubin level below 1.0 mg/dL postoperatively. Liver biopsies taken from 31 infants with biliary atresia at the time of hepatic portoenterostomy between 1988 and 2002 were examined for immunohistochemistry and histology with H&E staining. The degree of GcRalpha expression in the biliary epithelium was semiquantitatively analyzed using staining scores. The histology features of the liver biopsy were also semiquantitatively analyzed by using the same scores to evaluate the liver injury. Intravenous prednisolone dosage was started with 4 mg/kg per day and tapered by a half dose every 2 days. The protocol was orally repeated during admission until the stool became constantly cholic. Statistical analysis was performed using Mann-Whitney U test and Spearman correlation coefficient by rank. Significance is set at a 95% confidence interval (P < .05).
  
  
  RESULTS
  There was a significant positive correlation between the liver histology and the GcRalpha scores in all patients with biliary atresia (P = .0128; r = 0.429). In group 1, there was a significant positive correlation between the GcRalpha expression scores and the total dose of prednisolone administered (P = .0063; r = 0.767).
  
  
  CONCLUSIONS
  The increase and degree of GcRalpha expression were associated with the severity of liver injury and may correlate with the dose of prednisolone required to sustain bile flow after successful hepatic portoenterostomy.
authors.affiliation: Division of Pediatric Surgery, Kobe Children's Hospital, Kobe 654-0081, Japan. tatekawa3966@s5.dion.ne.jp
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Tatekawa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Muraji
authors.forename: Chikara
authors.initials: C
authors.lastname: Tsugawa
mesh_terms: D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000378:metabolism*; D001656:Biliary Atresia / Q000188:drug therapy / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology; D011239:Prednisolone / Q000627:therapeutic use; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis* / Q000187:drug effects; D012720:Severity of Illness Index
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D011239:Prednisolone