The Role of Bile Salt Toxicity in the Pathogenesis of Bile Duct

Tag : from porcine

Abstract:
Background. Intrahepatic bile duct strictures are a seriouscomplication after non-heart-beating (NHB) liver transplantation.Bile salt toxicity has been identified as an important factor inthe pathogenesis of bile duct injury and cholangiopathies. The roleof bile salt toxicity in the development of biliary stricturesafter NHB liver transplantation is unclear.
Methods. In a porcine model of NHB liver transplantation, westudied the effect of different periods of warm ischemia in thedonor on bile composition and subsequent bile duct injury aftertransplantation. After induction of cardiac arrest in the donor,liver procurement was delayed for 0 min (group A), 15 min (groupB), or more or equal to 30 min (group C). Livers were subsequentlytransplanted after 4 hr of cold preservation. In the recipients,bile flow was measured, and bile samples were collected daily todetermine the bile salt-to-phospholipid ratio. Severity of bileduct injury was semiquantified by using a histologic grading scale.
Results. Posttransplantation survival was directly related to theduration of warm ischemia in the donor. The bilesalt-to-phospholipid ratio in bile produced early aftertransplantation was significantly higher in group C, compared withgroup A and B. Histopathologic condition showed the highest degreeof bile duct injury in group C.
Conclusion. Prolonged warm ischemia in NHB donors is associatedwith the formation of toxic bile after transplantation, with a highbiliary bile salt-to-phospholipid ratio. These data suggest thatbile salt toxicity contributes to the pathogenesis of bile ductinjury after NHB liver transplantation.
(C) 2008 Lippincott Williams & Wilkins, Inc.