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Rejection of pig liver xenografts in patients with liver failure: Implications for xenotransplantation
Author(s) -
Tector A. Joseph,
Berho Mariana,
Fridell Jonathan A.,
DiCarlo Antonio,
Liu S.,
Soderland Carl,
Barkun Jeffrey S.,
Metrakos Peter,
Tchervenkov Jean I.
Publication year - 2001
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1053/jlts.2001.21281
Subject(s) - xenotransplantation , medicine , liver transplantation , miniature pig , bioartificial liver device , liver injury , pig liver , transplantation , complement system , pathology , antibody , immunology , hepatocyte , biology , in vitro , surgery , biochemistry , enzyme
The pathophysiological state of rejection in liver xenotransplantation is poorly understood. Data from clinical pig liver perfusion suggest that pig livers might be rejected less vigorously than pig hearts or kidneys. Pig livers used in clinical xenoperfusions were exposed to blood from patients with liver failure. We have shown in an animal model that transplant recipients with liver failure are less capable of initiating hyperacute rejection of a xenografted liver than a healthy transplant recipient. The goal of this report is to examine the pathological characteristics of pig livers used in 2 clinical pig liver perfusions and combine this information with in vitro studies of pig‐to‐human liver xenotransplantation to determine whether the findings in the perfused pig livers could be explained in part by the diminished capacity of the patient with liver failure to respond to xenogeneic tissue. Pathological analysis of the perfused pig livers showed immunoglobulin M deposition in the sinusoids with little evidence of complement activation. Our in vitro studies showed that serum from patients with liver failure caused less injury to pig liver endothelium than serum from healthy subjects. Serum from patients with liver failure had similar levels of xenoreactive antibodies as serum from healthy humans. Incubation of serum from patients with liver failure with pig hepatic endothelial cells generated less iC3b, Bb fragment, and C5b‐9 than serum from healthy subjects. We conclude that the altered injury in the perfused pig livers can be attributed to the relative complement deficiency that accompanies liver failure.