PREDNISONE WITHDRAWAL 14 DAYS AFTER LIVER-TRANSPLANTATION WITH MYCOPHENOLATE - A PROSPECTIVE TRIAL OF CYCLOSPORINE AND TACROLIMUS

Background The long-term complications of immunosuppressive therapy su ch as diabetes, hypercholesterolemia, and hypertension are a major sou rce of morbidity in liver transplant recipients, In this prospective, randomized, open-label study we completely withdrew prednisone (PRED) 14 days after Liver transplantation in an effort to decrease these met abolic complications, Patients were maintained on mycophenolate mofeti l (MMF) in combination with either cyclosporine (CsA; Neoral formulati on) or tacrolimus (TAG), Thus, we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy, toxicity, an d effect on posttransplant metabolic complications, Methods, A total o f 71 patients were randomized to receive either TAC-MMF (n=35) or CsA- MMF (n=36) after liver transplantation and were analyzed for patient a nd graft survival, Fifty-eight patients continued the immunosuppressiv e protocol for at least 6 months after transplantation and were analyz ed for the incidence of acute rejection and the prevalence of diabetes , hypertension, and hypercholesterolemia. Results, The 6-month patient survival rates were 94.4% for CsA-MMF and 88.6% for TAC-MMF. Correspo nding 6-month graft survival rates were 88.7% and 85.7% with no immuno logic graft losses in either group, The incidence of biopsy-proven acu te rejection was 46% for CsA-MMF and 42.3% for TAC-MMF. Six patients w ere converted from CsA to TAC (four for recurrent rejection) and seven patients were converted from TAC to CsA (four for neurotoxicity), Onl y one patient (in the TAC-MMF group) developed new-onset posttransplan t diabetes, In contrast, four of eight patients in the CsA-MMF group w ho were diabetic before transplant became nondiabetic in the first 3 m onths after transplant, The mean serum cholesterol level was significa ntly lower in the TAC-MMF group than in the CsA-MMF group (145.2+/-41. 8 mg/dl and 190.3+/-62.2, respectively; P<0.001) and the incidence of hypertension was lower in the TAC-MMF group (12% vs, 30.3% in the CsA- MMF group, P<0.01), Both groups had a lower incidence of metabolic com plications compared with a historical group (n=100) maintained on CsA and PRED (10 mg/day at 6 months), Conclusions, MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver trans plantation with a moderate rejection rate and no immunologic graft los ses, Early PRED withdrawal decreases posttransplant diabetes, hypercho lesterolemia, and hypertension, but patients maintained on TAC have lo wer serum cholesterol levels and a lower incidence of hypertension tha n CsA-treated patients.