Background and prognostic implications of perireperfusion tissue injuries in human liver transplants - A panel histochemical study

Background. Hepatic graft reperfusion is associated with inflammatory processes of unknown relevance to the fate of graft. This study aimed to clarify this relevance by histochemical analyses of human hepatic grafts. Methods. Paired tissue samples were taken at the end of cold preservation and 2 hr after reperfusion (n=39). From six additional grafts, biopsies were performed at the end of cold preservation only. Injury or inflammatory markers of sinusoidal endothelium (von Willebrand factor-related antigen [vWF]), Kupffer cells (25F9), platelets (CD62), neutrophil leukocytes (CD11b), interleukin (IL)-1 beta, intercellular adhesion molecule (ICAM)-1, and HLA-DR were evaluated semiquantitatively by indirect immunoperoxidase staining. Steatosis was also evaluated by hematoxylin and eosin staining. Results. vWF, CD62(+) platelet aggregation, CD11b(+) leukocytes, and IL-1 beta levels increased after reperfusion, and these levels correlated with prereperfusion levels. Not only vWF, CD62(+) platelets, CD11b(+) leukocytes, IL-1 beta, ICAM-1, and steatosis after reperfusion, but also IL-1 beta, ICAM-1, and steatosis before reperfusion correlated with postoperative peak transaminase. Furthermore, vWF, CD11b(+) leukocytes, 25F9(+) macrophages, and ICAM-1 after reperfusion were associated with primary graft nonfunction and strong expressions of ICAM-1 or HLA-DR with early acute rejection. Although some markers (IL-1 beta, CD62(+) platelets, and CD11b(+) leukocytes) correlated with preharvesting parameters (donor age or length of intensive care unit stay), none showed any significant correlation with cold preservation. Conclusion. Synergistic inflammatory events in the hepatic graft at reperfusion, which have a significant impact on the later clinical course, are largely defined and precipitated by injury or activation of nonparenchymal cells preceding reperfusion or even graft harvesting.