T. Ha

NO IMMUNOLOGIC GRAFT FAILURE IN CONSECUTIVE 17 CASES OF ABO-INCOMPATIBLE LIVING DONOR LIVER TRANSPLANTATION UNDER RITUXIMAB PROPHYLAXIS: 862

(Introduction) The use of ABO-incompatible (ABOi) donors in living donor liver transplantation (LDLT) can expand the donor pool in countries with an extreme scarcity of deceased donor organs. Risks to the donor can be justified only by an acceptable outcome to the recipient, but early outcomes of ABOi LDLT were not encouraging, with success only in pediatric cases. However, advances in preventative measures for antibody-mediated rejection (AMR) have lowered the incidence of AMR and improved survival outcomes. We describe here our initial experiences and early results with 17 patients who underwent ABOi LDLT in our center from December 2008 to February 2010. (Methods) Each patient received a single dose of rituximab (375 mg/mm2 of body surface area) 2 weeks prior to liver transplantation (LT). The frequency and timing of plasma exchange, with blood-type AB fresh frozen plasma, depended on hemagglutinin (HA) titer, aiming at an antibody titer of 1:8 or less before LT. Intravenous methylprednisolone (10 mg/kg) was administered just before reperfusion and continued through a catheter as local infusion therapy, followed by oral methylprednisolone, starting at a dose of 0.5 mg/kg/day and tapered over the 3 months after LDLT. Patients were treated with intravenous cyclophosphamide (2 mg/kg/day) for 1week, followed by oral mycophenolate mofetil (500 mg twice daily). Local infusion therapy (LIT) consisted of hepatic arterial or portal vein infusion. Methylprednisolone (125 mg/day for 1 week and 50 mg/day for the following week) and prostaglandin E1 (0.01 mg /kg/minute for 3 weeks) was administered through the catheter. The spleen was preserved in all cases. (Results) Mean patient age was 48.8 ± 5.9 years (range, 40~58 years), and mean MELD score was 15.5 ± 4.9 (range, 8~25). Fourteen patients underwent LT for hepatitis B virus-associated liver cirrhosis (LC), with three of these patients also having hepatocellular carcinoma. Of the remaining three patients, one each underwent LT for alcoholic LC, hepatitis C virus-associated LC, and Wilson’s disease. The graft types included 12 modified right lobe grafts, 4 dual grafts, and 1 left lobe-plus-caudate lobe graft. The mean graft weight-to recipient weight ratio was 1.1 ± 0.2 % (range 0.8%~1.4%). Rituximab was administered to all patients at a mean of 14.7 ± 4.9 days (range, 10~28 days) before LT. All 17 patients also received tacrolimus to maintain immunosuppression. Preoperative PE was performed a mean 3.5 ± 1.6 times (range, 1~8 times) and postoperative PE was performed a mean 1.5 ± 2.0 times (range, 0~5 times). There were eight episodes of postoperative complication including LIT catheter-related complications in six patients. There 4 cases of biliary complication in 3 patients. Among them, intractable multiple intrahepatic biliary strictures caused mortality on postoperative 4th month. Portal vein and hepatic vein stenosis occurred in 1 patient. Pneumonia including bacterial, fungal and tuberculous pneumonia occurred in 4 patients. Cholangitis occurred in 3 patients. But, there was no immunologic graft failure. Total 8 episodes of liver biopsy were performed in 4 patients due to abnormal liver function test. And there was no episode revealing AMR. (Conclusion) ABOi ALDLT may be feasible for patients with endstage liver disease in countries with a shortage of deceased donors, if no ABOc donors are available. Our results suggest that the successful prophylaxis with rituximab, to inhibit postoperative HA increase, and good preoperative condition of the patient, may enhance patient outcomes.