Altered bile composition after liver transplantation is associated with the development of nonanastomotic biliary strictures.
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.
Buis
Carlijn I
CI
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.
Geuken
Erwin
E
Visser
Dorien S
DS
Kuipers
Folkert
F
Haagsma
Elizabeth B
EB
Verkade
Henkjan J
HJ
Porte
Robert J
RJ
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
D001647:Bile Acids and Salts; D010743:Phospholipids; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase