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

Authors

  • Marián Kukan,

    1. Laboratory of Perfused Organs, Slovak Centre for Organ Transplantation, Institute of Preventive and Clinical Medicine, Bratislava, Slovakia
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  • PhD Pierre S. Haddad

    Corresponding author
    1. Groupe de Recherche en Transport Membranaire et Département de Pharmacologie, Université de Montréal, Montréal, Quebec, Canada
    • Département de Pharmacologie, Université de Montréal, CP 6128, Succursalle Centreville, Montréal, QC H3C 3J7, Canada. Telephone: 514-343-6590; FAX: 514-343-2291
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Abstract

In liver transplantation, it is currently hypothesized that nonparenchymal cell damage and/or activation is the major cause of preservation-related graft injury. Because parenchymal cells (hepatocytes) appear morphologically well preserved even after extended cold preservation, their injury after warm reperfusion is ascribed to the consequences of nonparenchymal cell damage and/or activation. However, accumulating evidence over the past decade indicated that the current hypothesis cannot fully explain preservation-related liver graft injury. We review data obtained in animal and human liver transplantation and isolated perfused animal livers, as well as isolated cell models to highlight growing evidence of the importance of hepatocyte disturbances in the pathogenesis of normal and fatty graft injury. Particular attention is given to preservation time-dependent decreases in high-energy adenine nucleotide levels in liver cells, a circumstance that (1) sensitizes hepatocytes to various stimuli and insults, (2) correlates well with graft function after liver transplantation, and (3) may also underlie the preservation time-dependent increase in endothelial cell damage. We also review damage to bile duct cells, which is increasingly being recognized as important in the long-lasting phase of reperfusion injury. The role of hydrophobic bile salts in that context is particularly assessed. Finally, a number of avenues aimed at preserving hepatocyte and bile duct cell integrity are discussed in the context of liver transplantation therapy as a complement to reducing nonparenchymal cell damage and/or activation.

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