Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

E Geuken; D Visser; F Kuipers; H Blokzijl; HGD Leuvenink; KP de Jong; PMJG Peeters; PLM Jansen; MJH Slooff; ASH Gouw; RJ Porte

doi:10.1016/j.jhep.2004.08.023

Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

E Geuken, D Visser, F Kuipers, H Blokzijl, HGD Leuvenink, KP de Jong, PMJG Peeters, PLM Jansen, MJH Slooff, ASH Gouw, RJ Porte^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

96 Citations (Scopus)

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. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Original language	English
Pages (from-to)	1017-1025
Number of pages	9
Journal	Journal of Hepatology
Volume	41
Issue number	6
DOIs	https://doi.org/10.1016/j.jhep.2004.08.023
Publication status	Published - Dec-2004

Keywords

liver transplantation
hepatobiliary function
hepatoxicity
cholestasis
biliary complications
bile salt
ISCHEMIA-REPERFUSION INJURY
P-GLYCOPROTEIN GENE
BILIARY STRICTURES
COLD PRESERVATION
RAT-LIVER
CHOLESTASIS
DISEASE
CELLS
TIME
URSODEOXYCHOLATE

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@article{9ad0ebbee64c49019582e7191549aaac,

title = "Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation",

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. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",

keywords = "liver transplantation, hepatobiliary function, hepatoxicity, cholestasis, biliary complications, bile salt, ISCHEMIA-REPERFUSION INJURY, P-GLYCOPROTEIN GENE, BILIARY STRICTURES, COLD PRESERVATION, RAT-LIVER, CHOLESTASIS, DISEASE, CELLS, TIME, URSODEOXYCHOLATE",

author = "E Geuken and D Visser and F Kuipers and H Blokzijl and HGD Leuvenink and {de Jong}, KP and PMJG Peeters and PLM Jansen and MJH Slooff and ASH Gouw and RJ Porte",

year = "2004",

month = dec,

doi = "10.1016/j.jhep.2004.08.023",

language = "English",

volume = "41",

pages = "1017--1025",

journal = "Journal of Hepatology",

issn = "0168-8278",

publisher = "ELSEVIER SCIENCE BV",

number = "6",

}

TY - JOUR

T1 - Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

AU - Geuken, E

AU - Visser, D

AU - Kuipers, F

AU - Blokzijl, H

AU - Leuvenink, HGD

AU - de Jong, KP

AU - Peeters, PMJG

AU - Jansen, PLM

AU - Slooff, MJH

AU - Gouw, ASH

AU - Porte, RJ

PY - 2004/12

Y1 - 2004/12

N2 - 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. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

AB - 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. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

KW - liver transplantation

KW - hepatobiliary function

KW - hepatoxicity

KW - cholestasis

KW - biliary complications

KW - bile salt

KW - ISCHEMIA-REPERFUSION INJURY

KW - P-GLYCOPROTEIN GENE

KW - BILIARY STRICTURES

KW - COLD PRESERVATION

KW - RAT-LIVER

KW - CHOLESTASIS

KW - DISEASE

KW - CELLS

KW - TIME

KW - URSODEOXYCHOLATE

U2 - 10.1016/j.jhep.2004.08.023

DO - 10.1016/j.jhep.2004.08.023

M3 - Article

SN - 0168-8278

VL - 41

SP - 1017

EP - 1025

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 6

ER -