Development of AKI within the first 72 h after transplant impacted short-term and long-term graft survival.

The greatest part of liver allograft injury occurs during reperfusion, not during the cold ischemia phase. The aim of this study, therefore, was to investigate how the severity of postreperfusion syndrome (PRS) influences short-term outcome for the patient and for the liver allograft. Over a 2-year period, 338 consecutive patients who presented for orthotopic liver transplantation (OLT) were included in this retrospective study. They were divided into 2 groups according to the severity of the PRS they experienced. The first group comprised 152 patients with mild or no PRS; the second group comprised 186 patients with significant PRS. Perioperative hemodynamic parameters, coagulation profiles, blood product requirements, incidence of infection, incidence of rejection and outcome data for both groups were collected and analyzed. There was no demographic difference between the groups except for age; group 2 had older patients than group 1 (54.94 Ϯ 9.07 versus 51.52 Ϯ 9.91, P ϭ 0.001). Compared to group 1, group 2 patients required more red blood cell transfusions (11.31 Ϯ 10.90 versus 8.08 Ϯ 7.89 units, P ϭ 0.002), more fresh frozen plasma transfusions (10.25 Ϯ 10.96 versus 7.03 Ϯ 7.64 units, P ϭ 0.002), more cryoprecipitate (1.88 Ϯ 4.72 units versus 0.61 Ϯ 1.80 units, P ϭ 0.001), and were more likely to suffer from fibrinolysis (52.7% versus 41.4%, P ϭ 0.041). Interestingly, group 2 had a shorter average warm ischemia time than group 1 (33.19 Ϯ 8.55 versus 36.21 Ϯ 11.83 minutes, P ϭ 0.01). Group 2 also required longer, on average, mechanical ventilation (14.95 Ϯ 29.79 versus 8.55 Ϯ 17.79 days, P ϭ 0.015), remained in the intensive care unit longer (17.65 Ϯ 31.00 versus 11.49 Ϯ 18.67 days, P ϭ 0.025), and had a longer hospital stay (27.29 Ϯ 32.35 versus 20.85 Ϯ 21.08 days, P ϭ 0.029). Group 2 was more likely to require retransplantation (8.6% versus 3.3%, P ϭ 0.044). In conclusion, the severity of PRS during OLT appears to be related to the outcome of patient and liver allograft.

Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this doubleblind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 g/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required. (Liver Transpl 2005;11:895-900.)

Objective To minimize maintenance immunosuppression in upper-extremity transplantation to favor the risk-benefit balance of this procedure. Background Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the risks and side effects of multidrug immunosuppression. We present our experience with upper-extremity transplantation under a novel, donor bone marrow (BM) cell-based treatment protocol (“Pittsburgh protocol”). Methods Between March 2009 and September 2010, 5 patients received a bilateral hand (n = 2), a bilateral hand/forearm (n = 1), or a unilateral (n = 2) hand transplant. Patients were treated with alemtuzumab and methylprednisolone for induction, followed by tacrolimus monotherapy. On day 14, patients received an infusion of donor BM cells isolated from 9 vertebral bodies. Comprehensive follow-up included functional evaluation, imaging, and immunomonitoring. Results All patients are maintained on tacrolimus monotherapy with trough levels ranging between 4 and 12 ng/mL. Skin rejections were infrequent and reversible. Patients demonstrated sustained improvements in motor function and sensory return correlating with time after transplantation and level of amputation. Side effects included transient increase in serum creatinine, hyperglycemia managed with oral hypoglycemics, minor wound infection, and hyperuricemia but no infections. Immunomonitoring revealed transient moderate levels of donor-specific antibodies, adequate immunocompetence, and no peripheral blood chimerism. Imaging demonstrated patent vessels with only mild luminal narrowing/occlusion in 1 case. Protocol skin biopsies showed absent or minimal perivascular cellular infiltrates. Conclusions Our data suggest that this BM cell-based treatment protocol is safe, is well tolerated, and allows upper-extremity transplantation using low-dose tacrolimus monotherapy.

In an attempt to more completely define the histopathologic features of the portal vein hyperperfusion or small-for-size syndrome (PHP/SFSS), we strictly identified 5 PHP/SFSS cases among 39 (5/39; 13%) adult living donor liver transplants (ALDLT) completed between 11/01 and 09/03. Living donor segments consisting of 3 right lobes, 1 left lobe, and 1 left lateral segment, with a mean allograft-to-recipient weight ratio (GRWR) of 1.0 +/- 0.3 (range 0.6 to 1.4), were transplanted without complications, initially, into 6 relatively healthy 25 to 63-year-old recipients. However, all recipients developed otherwise unexplained jaundice, coagulopathy, and ascites within 5 days after transplantation. Examination of sequential posttransplant biopsies and 3 failed allografts with clinicopathologic correlation was used in an attempt to reconstruct the sequence of events. Early findings included: (1) portal hyperperfusion resulting in portal vein and periportal sinusoidal endothelial denudation and focal hemorrhage into the portal tract connective tissue, which dissected into the periportal hepatic parenchyma when severe; and (2) poor hepatic arterial flow and vasospasm, which in severe cases, led to functional dearterialization, ischemic cholangitis, and parenchymal infarcts. Late sequelae in grafts surviving the initial events included small portal vein branch thrombosis with occasional luminal obliteration or recanalization, nodular regenerative hyperplasia, and biliary strictures. These findings suggest that portal hyperperfusion, venous pathology, and the arterial buffer response importantly contribute to early and late clinical and histopathologic manifestations of the small-for-size syndrome.