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Posttransplant chronic renal failure, secondary to calcineurin inhibitor agents, is emerging as a major problem in liver transplantation. We report a randomized clinical trial comparing daclizumab, delayed low-dose tacrolimus (target trough level 4-8 ng/mL, starting day 4-6), Investigational Arm (n = 72), to standard tacrolimus induction/maintenance dosing, Standard Arm (n = 76), with mycophenolate mofetil and tapering corticosteroids in both study arms. The end-points were renal function indicated by the Modification of Diet in Renal Disease (MDRD). There was no significant difference in patient survival (86.6% Investigational Arm vs. 92.9% Standard Arm; P = 0.21) or acute rejection (23.2% vs. 27.7%, respectively; P = 0.68). Statistically significant differences in median glomerular filtration rate (GFR) were found in favor of the Investigational Arm. With the CG equation, the GFR at the end of the first week was 110.7 vs. 89.6 mL/min (P = 0.019) without significant differences thereafter. With the MDRD, statistically significant differences extended to the first posttransplant month (86.8 vs. 70.1 mL/min/1.73 m(2); P < 0.001) with and was seen at month 6 (75.4 vs. 69.5 mL/min/1.73 m(2); P = 0.038). In conclusion, delayed low-dose tacrolimus, in combination with daclizumab and mycophenolate mofetil, preserves early renal function post-liver transplantation without the cost of increased acute rejection.

Because of the increasing gap in the number of patients awaiting organ transplantation and the supply of organ donors, reevaluation of donor criteria is an important issue in clinical transplantation. It has become necessary to make maximal use of the currently available donor pool. We describe a case of successful orthotopic liver transplantation in a 57-year-old man with Laënnec's cirrhosis using a liver containing an 8-cm focal nodular hyperplasia (FNH) lesion involving segments II and III and the caudate lobe. The donor liver was procured from a 46-year-old woman declared brain dead after a subarachnoid hemorrhage. Definitive pathological diagnosis was made at laparotomy by obtaining a Tru-cut (Allegiance Health Care Inc, Toronto, Ontario, Canada) core biopsy specimen. The recipient operation was performed uneventfully except for bleeding from the biopsy site. The patient did well postoperatively and was discharged on tacrolimus, mofetil mycophenolate, and prednisone therapy. He continues to thrive 2(1/2) years posttransplantation with no change in the size of the lesion. In well-selected donors, FNH should not be a contraindication for use in transplantation. However, FNH must be differentiated from hepatocellular adenoma. Although FNH has a benign course with little propensity for bleeding and almost no malignant potential, hepatic adenoma is reported to have a 15% to 33% chance of bleeding and rupture with a well-documented potential for neoplastic degeneration, making the liver unsuitable for donation.

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.