Korean J Pathol.  2009 Feb;43(1):48-55. 10.4132/KoreanJPathol.2009.43.1.48.

Alteration of Bile Acid Transporter Expression in Patients with Early Cholestasis Following Living Donor Liver Transplantation

Affiliations
  • 1Department of Hospital Pathology, The Catholic University of Korea, Seoul, Korea.
  • 2Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea. jychoi@catholic.ac.kr
  • 3Department of Chemistry, Dongguk University, Seoul, Korea.
  • 4Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 5Hepatology Center, Bundang Jesaeng General Hospital, Seongnam, Korea.

Abstract

BACKGROUND
Intrahepatic cholestasis can occur early after living donor liver transplantation (LDLT). We investigated the changes in the expressions of the bile acid transporters and the liver histology in the patients who suffered with early cholestasis (EC) following LDLT.
METHODS
The histological differences between 15 graft livers with EC after LDLT and 5 graft livers with biliary stricture following LDLT were evaluated. The hepatic mRNA levels of the bile canaliculi transporters (BSEP, MRP2, MRP3, MDR1, MDR3, NTCP) in 40 (20 graft livers, 20 matched donor livers) liver biopsy tissues were analyzed by performing real-time reverse-transcription polymerase chain reaction (RT-PCR).
RESULTS
Microscopic examination revealed hepatocellular and/or bile canalicular cholestasis around acinar zone 3 in the livers of the patients with EC. In the livers with biliary stricture, the cholestasis was dominantly observed in the hepatocytic cytoplasm and in the bile ductules around the portal area rather than around acinar zone 3. The BSEP and MRP2 mRNA levels in the EC livers were significantly reduced by 44% and 23%, respectively (p=0.000), compared to the matched donor livers. The levels of MDR3 and NTCP mRNA in the EC livers increased by 738% (p=0.000) and 281% (p<0.01), respectively. The change of the expressions of the bile acid transporters in the patients with biliary stricture was less significant than that in the EC group.
CONCLUSIONS
These results suggest that the altered expressions of the bile acid transporters may play a role in the pathogenesis of EC following LDLT.

Keyword

Cholestasis; Liver transplantation; Bile acid transporter

MeSH Terms

Bile
Bile Canaliculi
Biopsy
Carrier Proteins
Cholestasis
Cholestasis, Intrahepatic
Constriction, Pathologic
Cytoplasm
Humans
Liver
Liver Transplantation
Living Donors
Membrane Glycoproteins
Polymerase Chain Reaction
RNA, Messenger
Tissue Donors
Transplants
Carrier Proteins
Membrane Glycoproteins
RNA, Messenger
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