Cold storage and ischemia-reperfusion injury during liver transplantation influences epithelial architecture of the bile duct

Introduction: Biliary complications remain a major cause of graft failure after liver transplantation. In part, these problems result from ischemia-reperfusion injury. Between biliary epithelial cells tight junction proteins play an essential role for permeability and barrier function. Our aim was to examine the influence of cold storage and ischemia-reperfusion in liver transplantation on biliary epithelial cell architecture. Material and Methods: We examined common bile ducts from liver grafts immediately after organ explantation, and following reperfusion of the transplanted liver. Healthy bile ducts served as controls. Tissue specimens were examined by H&E staining and fluorescence immunohistochemistry for Tight junction protein 1 (TJP1), Claudin 1 (Cl1) and the proliferation marker Ki67. Results: ontrol sections showed intact morphology of the epithelium with consistent localization of TJP1 and Cl1 at the apical end of the biliary epithelial cells. Further, low expression of Ki67 could be detected (13.3%+-2.8% of cells), indicating proliferation of the biliary epithelium. In addition, sections obtained immediately after organ explantation displayed regular morphology and high proliferative activity of the biliary epithelium measured by Ki67 immunohistochemistry. In contrast, the epithelial architecture of the bile duct following reperfusion was partially destroyed. TJP1 and Cl1 could not be detected with an appropriate morphologic pattern and virtually no proliferating biliary epithelial cells were present (1%+-0.58% of cells, p=0.132). Conclusion: Cold storage and ischemia-reperfusion injury during liver transplantation causes damage to the biliary epithelium and destruction of tight junction morphology leads to reduced barrier function of the epithelium. In addition, the absence of Ki67 following reperfusion suggests that the regenerative function of epithelial cells is impaired. This may represent a reason for biliary complications following liver transplantation.