A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies

Abstract

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 histopathological 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 less than 0.05) and within 10 days of transplantation (p less than 0.01). They also had a higher incidence of graft failure in the first 180 days (p less than 0.01). Hyperacute rejection with necrotizing or neutrophilic arteritis was not seen in the crossmatch-positive 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.

Fig. 1

Postoperative platelet counts (PLT) and liver function test values for total bilirubin (TB), AST, alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (GGTP). n = 18 for each point in the crossmatch-positive group and n = 46 for the crossmatch-negative patients.

Fig. 2

Postreperfusion needle biopsy specimen from orthotopic liver transplantation no. 2284 demonstrating platelet margination along the central vein endothelium and in the lumen. This finding was most common in the crossmatch-positive patients immediately after reperfusion and was identical to that observed in sensitized rodents (Nakamura K, et al, Manuscript submitted, 1992). (H & E; original magnification × 768.)

Fig. 3

Needle biopsy specimen of liver allograft from orthotopic liver transplantation no. 2309, 17 days after transplantation. This biopsy specimen was obtained 9 days after treatment of acute cellular rejection. Note the marked cholangiolar proliferation. Centrilobular hepatocyte swelling was also present. These two findings are often attributed to preservation or ischemic injury but were much more common in the crossmatch-positive patients despite similar preservation times. (H & E; original magnification × 192.)

Fig. 4

Needle biopsy specimen of liver allograft from orthotopic liver transplantation no. 2284, 9 days after transplantation. Although portal localization of mononuclear cells has been emphasized as a component of cellular rejection, neutrophils, as a component of the population, were more common in the crossmatch-positive patients. (H & E; original magnification × 480.)

Fig. 5

Relationship between the cold ischemic time and the severity of preservation injury present in allograft biopsy specimens.

Fig. 6

Primary graft and patient survival curves for the crossmatch-positive patients vs. controls.

Fig. 7

Section of hilum of failed liver allograft from orthotopic liver transplantation no. 2474. Note the bile duct necrosis with bile leakage and intraluminal biliary sludge. An artery with the characteristic changes described above is present in the lower left corner. (H & E; orginal magnification × 77.)

Fig. 8

Section of failed liver allograft from orthotopic liver transplantation no. 2309, 54 days after transplantation. Note the marked medial thickening, luminal narrowing and medial myocyte vacuolization (indirect evidence of spasm). This finding was present in many, but not all, arteries in sections from the deep hilum of the liver. (H & E; original magnification × 480.)

Fig. 9

Ratio of arterial wall thickness to vessel diameter in failed grafts from crossmatch-positive patients vs. controls.