Liver Transplantation Across the ABO Barrier: The Role of Plasmapheresis A. Eid, G. Zamir, I. Yaron, E. Galun, R. Safadi, T. Schaaps, Y. Berlatzky, D. Shouval, and O. Jurim L IVER transplantation across the ABO barrier is usually contraindicated due to the increased risk of early graft loss secondary to hyperacute or severe cellular rejection. 1,2 In addition, these grafts are at increased risk of late loss due to chronic rejection, as well as to biliary and vascular complications. 3 Indeed, 1-year graft survival in this setting has been reported to range between 25% and 75%, signif- icantly worse than that of ABO-identical or -compatible grafts. 4–6 Nevertheless, these transplants are still unavoid- able at a time of severe shortage of organ donors, especially in urgent situations. Several therapeutic measures have been applied to help reduce antibody-mediated graft injury in ABO-mismatched liver recipients. These include donor-type plasma transfu- sion during surgery, immunosuppression with antithymo- cyte globulin (ATG) or OKT3 induction, infusion of soluble A or B antigens, splenectomy, and plasmapheresis. 7–9 The results of different centers regarding plasmapheresis con- flict. 1,9 In the present study, we report our center’s experi- ence with ABO-mismatched liver transplantation and the use of plasmapheresis. PATIENTS AND METHODS At the Hadassah Hebrew University Medical Center in Jerusalem, between October 1991 and August 1997, 48 patients underwent 51 orthotopic liver transplantations (OLT). During this period, seven OLTs were done for emergency indications: fulminant hepatitis of various etiologies (four patients), acute variceal bleeding and encephalopathy (one patient), and retransplant due to primary graft nonfunction (two patients). Four of these transplants were ABO mismatched; all of these recipients were blood type O receiving blood type A grafts (three patients) and a blood type B graft (one patient). The immunosuppressive protocol involved a sequential quadru- ple regimen, including ATG (one patient) and OKT3 (three patients) for 10 to 14 days, prednisone taper, azathioprine, and cyclosporine A (CyA), started between days 1 and 3. Bacterial prophylaxis of parenteral cefotaxime was administered for 48 hours after surgery and an oral bowel selective decontamination solution was used for 21 days. Viral prophylaxis of parenteral gancyclovir was administered during the hospital stay, with doses adjusted according to creatinine clearance. This was followed by oral acyclovir to 3 months posttransplantation. Plasmapheresis was used in all but our first patient. The anti-A and anti-B titers were assessed using reverse blood typing tests and the results were expressed as the reciprocal of the highest serum dilution (IgM and IgG). 10 Preoperative anti-A and anti-B antibody titers were available for all the patients, and ranged between 1/256 to 1/4098. These levels were monitored postoperatively in all patients until discharge. Donor-type plasmapheresis was used, with a continuous blood flow cell separator (COBE Spectra) via periph- eral vein access. Exchanges of 1 plasma volume (3 L) with normal saline and 5% albumin were anticipated at a 1 to 3-day interval. Plasmapheresis was continued for 7 to 22 days to maintain low hemagglutinin levels. The timing of the various medications was adjusted according to the plasmapheresis schedule. Episodes of graft rejection were diagnosed on clinical and biochemical grounds, and all were confirmed by liver biopsy. Dupplex ultrasonography was performed at days 1 and 7 and as clinically indicated. From the Department of Surgery and Transplantation Unit, the Liver Unit, Division of Internal Medicine,, Plasmapheresis Unit, Division of Hematology, and the Department of Vascular Sur- gery, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Address reprint requests to Ahmed Eid, MD, Department of Surgery and Transplantation Unit, Hadassah Hebrew University Medical Center, P.O. Box 12000, IL-91120, Jerusalem, Israel. Table 1. Demographic and Clinical Data, Outcome of ABO-Mismatched Liver Transplantations Patient Age of Donor and Recipient Diagnosis ABO of Donor and Recipient Cellular rejection (POD) HAT Bile Duct Injury Outcome 1 17–14 Fulminant hepatic failure A-O Severe (8) No No Alive at 6 y 2 22– 45 Retransplantation B-O Mild (8) Yes No Died at 40 mo 3 73–18 Fulminant Wilson’s disease A-O Mild (10) No Yes Died at 4 mo 4 38 –57 Retransplantation A-O Mild (10) No No Alive at 10 mo Abbreviations: POD, postoperative day. © 1998 by Elsevier Science Inc. 0041-1345/98/$19.00 655 Avenue of the Americas, New York, NY 10010 PII S0041-1345(98)00014-1 Transplantation Proceedings, 30, 701–703 (1998) 701