Evaluation of protocol before transplantation and after reperfusion biopsies from human orthotopic liver allografts: considerations of preservation and early immunological injury

Abstract

Light microscopic, immunohistochemical and ultrastructural analysis of protocol before transplantation and after reperfusion biopsy specimens from 87 randomly selected patients was performed to assess the contribution of preservation and immunological injury to early graft failure. Most biopsy specimens were essentially normal by light microscopy before transplantation, and no particular feature could be relied on to predict function after transplantation. Ultrastructural examination of biopsy specimens before transplantation demonstrated preferential degeneration of sinusoidal lining cells, but no strict correlation was seen between ultrastructural sinusoidal integrity before transplantation and function after transplantation. The presence of zonal or severe focal necrosis and a severe neutrophilic exudate in biopsy specimens after reperfusion presaged a poor early postoperative course in most, but not all, patients. The presence of preformed lymphocytotoxic antibodies had no effect on the early clinical course, but was associated with Kupffer cell hypertrophy in needle biopsy specimens taken after transplantation. No definite evidence was seen of hyperacute rejection as a result of preformed lymphocytotoxic antibodies as detected in conventional assays. These findings suggest that preservation injury accounts for only a subset of grafts that fail to function after transplantation. Other perioperative or "recipient" factors may be of equal or greater importance in early graft dysfunction or failure.

Fig. 1

Moderate diffuse hepatocellular swelling in a biopsy specimen after reperfusion. PT = portal tract. (H & E, original magnification × 100.)

Fig. 2

(a) Zonal necrosis associated with a severe neutrophilic infiltrate in centrizonal and periportal areas is seen in this biopsy specimen after reperfusion. CV = central vein, PT = portal tract. (H & E, original magnification × 100.) (b) Higher magnification demonstrates periportal zonal hepatocellular necrosis associated with a neutrophilic infiltrate. (H & E, original magnification × 250.)

Fig. 3

Plastic-embedded section of a biopsy specimen before transplantation obtained from a graft that exhibited histological evidence of damage after reperfusion. (a) The centrizonal sinusoidal lining cells demonstrate a rounded configuration instead of the slender elongated appearance (arrows) and focal denudation. The central vein endothelium is intact. CV = central vein. (Toluidine blue 0, original magnification × 250.) (b) Periportal sinusoidal lining cells (arrows) are less severely damaged in the same patient and the portal vein endothelium is intact. PV = portal vein; BD = bile duct. (Toluidine blue 0, original magnification × 250.) (c) Higher magnification of the centrizonal sinusoids demonstrates the endothelial cell damage (arrows) and hepatocellular blebs (arrow head) (Toluidine blue 0, original magnification × 1,000.)

Fig. 4

Electron microscopic findings in biopsy specimens before transplantation. (a) Demonstrates an area of well-maintained sinusoidal endothelial cells. EC = endothelial cell, arrows = space of Disse. (Original magnification × 4,700.) (b) Partial retraction of endothelial cells (EC) from the underlying tissue. H = hepatocytes, arrow = bleb. (Original magnification × 4,700.) (c) Inflammatory cells can be seen directly adherent to the hepatocytes (H) where the sinusoidal lining cells are denuded. Hepatocytes show cytoplasmic fat droplets, the other organelles are fairly well maintained. L = lymphocytes, N = neutrophil, EC = endothelial cell. (d) Sinusoidal platelets (P), cellular debris and fibrin deposition (arrow) were more easily detected in postreperfusion biopsy specimens from patients with a positive cross match. I = Ito cell. (Original magnification × 4,700.)