Preservation of human liver grafts in UW solution. Ultrastructural evidence for endothelial and Kupffer cell activation during cold ischemia and after ischemia-reperfusion.

Biopsies taken from 13 human liver grafts at different stages of the transplantation process were used for study of the morphology of sinusoidal cells prior to harvesting (5 biopsies), after preservation in UW solution (10 biopsies), and after complete revascularization (13 biopsies). The mean cold ischemic period was 12 h 30. Immediate follow up was uneventful and the mean peak of post-operative transaminases below 1300 IU/l. Biopsies were perfusion-fixed by the transparenchymal route to ensure satisfactory ultrastructural results. There were no loose sinusoidal endothelial cells in the lumen and no signs of cellular death. Some endothelial cells presented signs of activation at the end of the preservation period, and even more after revascularization, with numerous lucent vacuoles resembling endosomes in the cytoplasm. Kupffer cells also presented signs of activation, particularly after reperfusion. The retraction of endothelial cell processes which formed large gaps during cold ischemia proved to be partly reversible after reperfusion. Signs of endothelial cell damage with gaps and partial rupture of the plasmic membrane were also observed, particularly after revascularization, in areas which contained numerous inflammatory cells adhering to the wall. The Disse space was not generally enlarged and contained no inflammatory cells. The sinusoidal pole of hepatocytes was occasionally damaged with the formation of blebs. These results strongly suggest that any drug or preservation solution that will inhibit endothelial and Kupffer cell activation could be beneficial in the prevention of preservation and reperfusion injury.

Ultrastructure of human liver grafts preserved with UW solution. Comparison between patients with low and high postoperative transaminases levels.

We studied the morphology of sinusoidal cells on 21 human liver grafts prior to harvesting, at the end of the preservation period in UW solution, and after complete revascularization. The mean cold ischemic period was 11 h 34 min. Immediate follow-up was uneventful in 20 of these cases; 13 showed a mean peak of postoperative transaminases below 1,300 IU/L (group A), and 7 above 1,500 IU/L (group B). In the case of one patient (group C) steatosis was severe (50%) and there was serious postoperative dysfunction (transaminases 18,000 IU/L). Biopsies were perfusion-fixed by the transparenchymal route to ensure satisfactory ultrastructural results. In group A, some sinusoidal endothelial cells presented signs of activation at the end of the preservation period, and even more after revascularization. Kupffer cells also presented signs of activation particularly after reperfusion. Signs of endothelial cell damage with gaps and partial rupture of the plasmic membrane were also observed, particularly after revascularization in areas which contained numerous inflammatory cells adhering to the wall. The sinusoidal pole of hepatocytes was occasionally damaged, with the formation of blebs. In group B, adhesion of inflammatory cells to the sinusoidal wall was increased. Furthermore, in some areas with endothelial cell damage, neutrophils and platelets infiltrated the Disse space, and hepatocytes were increasingly damaged. In the case of patient C, the most obvious signs after reperfusion were hepatocyte drop out and death but there was no evidence of any concomitant sinusoidal cell damage. It would appear that even in cases where immediate follow-up is eventful, endothelial and Kupffer cells show signs of activation. This can be associated with signs of microcirculatory disturbances as was seen in 4 cases in group B. In the only case of severe steatosis that we studied, the essential sign was death of hepatocytes.