Role of hepatocytes and bile duct cells in preservation-reperfusion injuryof liver grafts

In liver transplantation, it is currently hypothesized that nonparenchymal cell damage and/or activation is the major cause of preservation-related gr aft injury, Because parenchymal cells (hepatocytes) appear morphologically well preserved even after extended cold preservation, their injury after wa rm reperfusion is ascribed to the consequences of nonparenchymal cell damag e and/or activation, However, accumulating evidence over the past decade in dicated that the current hypothesis cannot fully explain preservation-relat ed liver graft injury. We review data obtained in anima and human liver tra nsplantation and isolated perfused animal livers, as well as isolated cell models to highlight growing evidence of the importance of hepatocyte distur bances in the pathogenesis of normal and fatty graft injury. Particular att ention is given to preservation time-dependent decreases in high-energy ade nine nucleotide levels in liver cells, a circumstance that (1) sensitizes h epatocytes to various stimuli and insults, (2) correlates well with graft f unction after liver transplantation, and (3) may also underlie the preserva tion timedependent increase in endothelial cell damage. We also review dama ge to bile duct cells, which is increasingly being recognized as important in the long-lasting phase of reperfusion injury. The role of hydrophobic bi le salts in that context is particularly assessed, Finally, a number of ave nues aimed at preserving hepatocyte and bile duct cell integrity are discus sed in the context of Liver transplantation therapy as a complement to redu cing nonparenchymal cell damage and/or activation.