Roberto Lopez

First Clinical Use of a Novel Bioartificial Liver Support System (BLSS)

The first clinical use of the Excorp Medical Bioartificial Liver Support System (BLSS) in support of a 41‐year‐old African‐American female with fulminant hepatic failure is described. The BLSS is currently in a Phase I/II safety evaluation at the University of Pittsburgh/UPMC System. Inclusion criteria for the study are patients with acute liver failure, any etiology, presenting with encephalopathy deteriorating beyond Parsons Grade 2. The BLSS consists of a blood pump; a heat exchanger to control blood temperature; an oxygenator to control oxygenation and pH; a bioreactor; and associated pressure and flow alarm systems. Patient liver support is provided by 70–100 g of porcine liver cells housed in the hollow fiber bioreactor. The patient exhibited transient hypotension and thrombocytopenia at initiation of perfusion. The only unanticipated safety event was a lowering of patient glucose level at the onset of perfusion with the BLSS that was treatable with intravenous glucose administration. Moderate changes in blood biochemistries pre‐ and post perfusion are indicative of liver support being provided by the BLSS. While the initial experience with the BLSS is encouraging, completion of the Phase I/II study is required in order to more fully understand the safety aspects of the BLSS.

Safety observations in phase I clinical evaluation of the Excorp Medical Bioartificial Liver Support System after the first four patients.

A Phase I clinical safety evaluation of the Excorp Medical, Inc, Bioartificial Liver Support System (BLSS) is in progress. Inclusion criteria are patients with acute liver failure of any etiology, presenting with encephalopathy deteriorating beyond Parson’s Grade 2. The BLSS consists of a blood pump, heat exchanger to control blood temperature, oxygenator to control oxygenation and pH, bioreactor, and associated pressure and flow alarm systems. Patient liver support is provided by 70–100 g of porcine liver cells housed in the hollow fiber bioreactor. A single support period evaluation consists of 12 hour extracorporeal perfusion with the BLSS sandwiched between 12 hours of pre (baseline) and 12 hours of post support monitoring. Blood chemistries and hematologies are obtained every 6 hours during monitoring periods and every 4 hours during perfusion. Physiologic parameters are monitored continuously. The patient may receive a second treatment at the discretion of the clinical physician. Preliminary evaluation of safety considerations after enrollment of the first four patients (F, 41, acetaminophen induced, two support periods; M, 50, Wilson’s disease, one support period; F, 53, acute alcoholic hepatitis, two support periods; F, 24, chemotherapy induced, one support period) is presented. All patients tolerated the extracorporeal perfusion well. All patients presented with hypoglycemia at the start of perfusion, treatable by IV dextrose. Transient hypotension at the start of perfusion responded to an IV fluid bolus. Only the second patient required heparin anticoagulation. No serious or unexpected adverse events were noted. Moderate biochemical response to support was noted in all patients. Completion of the Phase I safety evaluation is required to fully characterize the safety of the BLSS.

One Thousand Consecutive Primary Liver Transplants Under Tacrolimus Immunosuppression: A 17- to 20-Year Longitudinal Follow-Up

Background. Tacrolimus has proven to be a potent immunosuppressive agent in orthotopic liver transplantation (OLT). The aim of this study is to examine its long-term efficacy and safety. Methods and Results. One thousand consecutive primary OLTs performed between August 1989 and December 1992 and maintained under tacrolimus-based immunosuppression were followed up until January 2009. Patient and graft survivals with corresponding causes of death and retransplantation, maintenance immunosuppression, and adverse effects were examined. The study population includes 600 males and 400 females comprising 166 children, 630 adults, and 204 seniors. The mean follow-up was 17.83 (range, 16.1–19.50) years. The overall 20-year actuarial patient and graft survivals were 35.8% and 32.6%, respectively. At the last follow-up, 442 patients were alive; 133 (77.1%) children, 265 (34.5%) adults, and 44 (16.1%) seniors (P=0.0001). After the first post-OLT year, cardiopulmonary events, recurrence of primary disease, and malignancy were the main causes of death. Overall, 183 recipients underwent retransplants; mainly for primary nonfunction, hepatic artery thrombosis, and recurrent primary disease, 180 required dialysis, and 45 underwent kidney transplant. A total of 97.7% of the survivors were on tacrolimus and 26.2% were also receiving adjunctive immunosuppressants at the last follow-up. Conclusions. The overall 20-year actuarial patient and graft survivals were 35.8% and 32.6%, respectively, with significantly better survival among children. Age-related complications, recurrence of primary disease, and malignancy were the major causes of late graft loss. Graft loss related to immunologic reasons was rare. The prevention of recurrent disease and newer immunosuppressive regimen will further improve these results.

52: POST-REPERFUSION SYNDROME IN LIVER TRANSPLANTATION

Learning Objectives: Post reperfusion syndrome (PRS) is a major and potentially lethal intraoperative event occurring in 20% of patients undergoing liver transplantation (LTx). PRS is characterized by significant hypotension and bradycardia following allograft implantation and it’s mainly exacerbated by ischemia-reperfusion injuries (IRI) stemming from liver procurement and preservation. A prospective preclinical study was conducted in a swine model comparing the post reperfusion events in 12 animals undergoing orthotopic LTx after 9 hours of cold ischemia time (CIT). Methods: The study group (n = 6) animals had their liver allografts (LA) preserved with machine perfusion (MP) combined with a hemoglobin-based oxygen carrier (HBOC) at 21°C. The control group (n = 6) had their LA preserved under cold storage (CS) with UW at 4°C. The animals had a 5-day post-transplant follow-up before the end-study necropsy. Results: The MP group had 100% survival and no signs of PRS, requiring significantly less intravenous fluid (p = 0.0061), blood products and vasopressors and demonstrative change in lactate. The CS group had 17% survival with moderate to severe signs of PRS. The MP group animals had a significantly (p < 0.05) higher bile secretion and urine output while displaying a significantly (p < 0.05) lower incidence of lactic acidosis and peak in liver enzymes (AST, ALT) during the postoperative period. The CS animals showed clear histological signs of moderate to severe IRI in their LA at the end-study necropsy, where massive centrilobular necrosis and cholestasis were documented. The MP animals had signs of none to mild IRI and normal LA function post-operatively. Conclusions: MP combined with HBOC at 21°C showed a significant (p < 0.05) decrease in the incidence of PRS in a swine model with CIT = 9 hours when compared to CS. MP provides effective ex-vivo oxygenation during LA preservation and significantly eliminates PRS in this challenging preclinical swine model. 52