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

Abstract

Background Biliary bile salts have been shown to contribute to bile duct injury after orthotopic liver transplantation (OLT). While 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), there is no formation on the expression of cholangiocyte transporters after OLT. We, therefore, examined the expression of cholangiocyte transporters in liver grafts and correlated this with the development of bile duct injury. Methods In 37 adult liver transplant recipients, biopsies were taken from the grafted liver: at the end of cold storage, 3hr after graft reperfusion and at one week after transplantation. Changes in the apical sodium-dependent bile salt transporter (ASBT), the organic solute transporters (OST-alpha and beta), and CFTR were assessed using real time RT-PCR and immunofluorescence staining. Gene expressions were correlated with biliary bile salt secretion as well as with the development of bile duct injury, as assessed by histology. Results Compared to normal controls, OST-alpha expression was significantly downregulated before transplantation and 3hr after graft reperfusion, but levels normalized at one week after OLT. OST-beta expression was more than 8-fold up-regulated at the time of transplantation and levels increased further during the first postoperative week. There were no major changes in the expression of CFTR. Expression of OST-alpha/ beta correlated with changes in biliary bile salt secretion. However, OST-alpha/beta and CFTR expression were not correlated with the development of microscopic bile duct injury after OLT. Conclusions Liver transplantation is associated with marked differential changes in the expression of the bile salt transporters OST-alpha and OST-beta, while CFTR expression remains stable. Although changes in OST-alpha/beta correlate with biliary bile salt secretion, OST-alpha/beta and CFTR do not correlate with the histological 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.nrpages: 20status: publishe