Changes in cholangiocyte bile salt transporter expression and bile duct injury after orthotopic liver transplantation

H. Hoekstra, S. Op Den Dries, C.I. Buis, A.A. Khan, A.S.H. Gouw, G.M.M. Groothuis, T. Lisman, R.J. Porte

OnderzoeksoutputAcademic

Samenvatting

Background: Bile salts have been shown to contribute to bile duct injury after orthotopic liver transplantation (OLT). Cholangiocytes modify bile composition by reabsorption of bile salts (cholehepatic shunt) and contribute to bile flow by active secretion of sodium and water via cystic fibrosis transmembrane conductance regulator (CFTR). We hypothesized that changes in these transporters may be associated with the development of bile duct injury after OLT. Aim: To examine the expression of cholangiocyte transporters in liver grafts and to correlate this with the development of bile duct injury. Methods: In 37 adult liver transplant recipients, liver biopsies were taken during and after OLT. Changes in the apical sodium-dependent bile salt transporter (ASBT), the organic solute transporters (OSTalpha and beta), and CFTR were assessed using real-time RT-PCR and immunofluorescence staining. Gene expressions were correlated with bile salt concentration as well as with the histological degree of bile duct injury. Results: Compared to normal controls, OSTalpha expression was significantly down-regulated at the end of cold storage and 3 hours after graft reperfusion, but levels normalized at one week after OLT. OSTbeta expression was more than 8-fold up-regulated at the time of transplantation and levels increased further during the first week. There were no major changes in the expression of CFTR. Expression of these transporters did not correlate with changes in bile salt concentration or with the development of bile duct injury after OLT. Conclusion: Liver transplantation is associated with changes in the expression of the bile salt transporters OST alpha and OST beta, while CFTR expression remains stable. Changes in OST alpha/beta do not correlate with bile salt concentration or the degree of bile duct injury, suggesting that the cholehepatic shunt does not play a major role in the development of bile salt induced bile duct injury after OLT.
Originele taal-2English
Pagina's (van-tot)173
Aantal pagina's1
TijdschriftHpb
Volume12
Nummer van het tijdschriftSupplement s1
DOI's
StatusPublished - 1-apr-2010

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