Twenty-six adult patients with preformed IgG donor lymphocytotoxic antibodies received primary liver allografts under FK 506 immunosuppression. The effect of the crossmatch-positive state on early graft function and on the immunopathological and histo-pathological findings was compared with that of 52 crossmatch-negative control recipients. The presensitized (Crossmatch-positive) patients had prolongation of early graft dysfunction, underwent more clinically indicated biopsies and had a higher incidence of cellular rejection, both overall (p < 0.05) and within 10 days of transplantation (p < 0.01). They also had a higher incidence of graft failure in the first 180 days (p < 0.01). Hyperacute rejection with necrotizing or neutrophilic arteritis was not seen in the crossmatchpositive grafts. However, histological findings associated with presensitization included platelet margination in central veins and sinusoids in biopsy specimens 60 to 90 min after graft revascularization. Later biopsy specimens had neutrophilic portal venulitis followed by cholangiolar proliferation, acute cholangiolitis and centrilobular hepatocyte swelling that mimicked preservation injury, endothelial activation of arteries with medial changes and relapsing episodes of acute cellular rejection. These clinicopathological observations suggest that lymphocytotoxic antibodies can have a deleterious effect on liver allograft function and survival, even if they do not precipitate immediate or hyperacute rejection. (Hepatology 1992;16:671-681.) Although the liver is known to be more resistant than other solid organs to injury from preformed graft antibodies in the recipient (1-3), this privileged state is not absolute (4,5). Identification of the consequences of humoral antibody states on the liver has been hampered by the lack of distinctive pathological findings in many cases in which humoral rejection was suspected but was not proved. Consequently, in this study of liver recipients with preformed donor lymphocytotoxic antibodies, we have attempted to determine whether a unique, pathologically identifiable form of graft injury could be recognized and whether pathophysiological mechanisms of liver allograft injury could be deduced. A similar study on the pathological nature of ABO-mismatched livers in which the graft antibodies were isoagglutinins was published recently (6).
MATERIALS AND METHODS
Patient SelectionDuring the 11-mo period between November 31, 1989, and September 9, 1990, 243 adult patients ( > 16 yr) were given primary liver allografts under FK 506 and low-dose steroid therapy. The sera of 26 (11%) contained donor lymphocytotoxic antibodies. The crossmatchnegative control patients (n = 52) were those treated just before and after the crossmatchpositive cases. Most of these same cases were part of a recent clinical report (5). There were no statistically significant differences between the two cohorts with respect to age, United Network of Organ Sharing urgency of need status, original disease, donor demographic data or...