title: Altered bile composition after liver transplantation is associated with the development of nonanastomotic biliary strictures.
abstract: OBJECTIVE
  Nonanastomotic biliary strictures are troublesome complications after liver transplantation. The pathogenesis of NAS is not completely clear, but experimental studies suggest that bile salt toxicity is involved.
  
  
  METHODS
  In one hundred and eleven adult liver transplants, bile samples were collected daily posttransplantation for determination of bile composition. Expression of bile transporters was studied perioperatively.
  
  
  RESULTS
  Nonanastomotic biliary strictures were detected in 14 patients (13%) within one year after transplantation. Patient and donor characteristics and postoperative serum liver enzymes were similar between patients who developed nonanastomotic biliary strictures and those who did not. Secretions of bile salts, phospholipids and cholesterol were significantly lower in patients who developed strictures. In parallel, biliary phospholipids/bile salt ratio was lower in patients developing strictures, suggestive for increased bile cytotoxicity. There were no differences in bile salt pool composition or in hepatobiliary transporter expression.
  
  
  CONCLUSIONS
  Although patients who develop nonanastomotic biliary strictures are initially clinically indiscernible from patients who do not develop nonanastomotic biliary strictures, the biliary bile salts and phospholipids secretion, as well as biliary phospholipids/bile salt ratio in the first week after transplantation, was significantly lower in the former group. This supports the concept that bile cytotoxicity is involved in the pathogenesis of nonanastomotic biliary strictures.
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Carlijn I
authors.initials: CI
authors.lastname: Buis
authors.forename: Erwin
authors.initials: E
authors.lastname: Geuken
authors.forename: Dorien S
authors.initials: DS
authors.lastname: Visser
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Haagsma
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Porte
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000737:chemistry* / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D001659:Biliary Tract / Q000378:metabolism / Q000473:pathology*; D002779:Cholestasis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D015331:Cohort Studies; D003251:Constriction, Pathologic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism; D011183:Postoperative Complications; D011446:Prospective Studies; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D010743:Phospholipids; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase