1. Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation.
- Author
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Geuken E, Visser D, Kuipers F, Blokzijl H, Leuvenink HG, de Jong KP, Peeters PM, Jansen PL, Slooff MJ, Gouw AS, and Porte RJ
- Subjects
- ATP Binding Cassette Transporter, Subfamily B genetics, ATP Binding Cassette Transporter, Subfamily B metabolism, ATP-Binding Cassette Transporters genetics, ATP-Binding Cassette Transporters metabolism, Bile metabolism, Fluorescent Antibody Technique, Humans, Membrane Transport Proteins genetics, Membrane Transport Proteins metabolism, Organic Anion Transporters, Sodium-Dependent genetics, Organic Anion Transporters, Sodium-Dependent metabolism, Phospholipids metabolism, Postoperative Period, RNA, Messenger metabolism, Symporters genetics, Symporters metabolism, Time Factors, Bile Acids and Salts metabolism, Bile Duct Diseases etiology, Liver metabolism, Liver Transplantation adverse effects
- Abstract
Background/aims: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation., Methods: In 28 liver transplant recipients, bile samples were collected daily posttransplantation for determination of bile composition. Hepatic expression of bile transporters was studied before and after transplantation. Histopathological criteria as well as biliary concentrations of alkaline phosphatase (ALP) and gamma-glutamyltransferase (gamma-GT) were used to quantify bile duct injury., Results: Early after transplantation, bile salt secretion increased more rapidly than phospholipid secretion, resulting in high biliary bile salt/phospholipid ratio (BA/PL). In parallel with this, mRNA levels of the bile salt transporters NTCP and BSEP increased significantly after transplantation, whereas phospholipid translocator MDR3 mRNA levels remained unchanged. Bile duct injury correlated significantly with bile salt secretion and was associated with a high biliary BA/PL ratio., Conclusions: Bile salt secretion after human liver transplantation recovers more rapidly than phospholipid secretion. This results in cytotoxic bile formation and correlates with bile duct injury. These findings suggest that endogenous bile salts have a role in the pathogenesis of bile duct injury after liver transplantation.
- Published
- 2004
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