Tacrolimus-based Immunosuppression After Orthotopic Liver Transplantation: A Randomised Study Comparing

ObjectiveBy comparing the efficacy and safety of oral tacrolimus-based(FK506-based) immunosuppression after orthotopic liver transplantation in adult, We hope to discover the reasonable regimen and suitably blood concentration of the drug to protect the graft liver effectively and reduce the toxic action largely.MethodsThe trial was the randomization, open and prospective analysis of a single center. From Feb. 2001 to July 2004, 94 adult recipients of cadaveric liver transplantation (LT) were divided into 3 groups randomizationly according to different tacrolimus-based immunosuppression (dual: FK506+prednisone; triple: FK506+MMF+prednisone; quadruple: FK506+MMF+prednisone+daclizumab;) and the quadruple therapy group was divided into 2 groups according to low or high blood concentration of FK506(respectively called QL group and QH group). The recipients were followed up for 6 months posttransplantation. The frequencies of acute rejection and graft survival rate were considered as the efficacy indexes. The safety indexes were: recipient survival rate, occurrence of hypertension, glycemia and tremor; the rates of infection of bacteria and CMV, reinfection of hepatic virus of type B; and the liver function, renal function, blood hemoglobin concentration, leukocyte,platelet, the level of blood liquid. ResultsComparing among of dual, triple, and quadruple therapy group: The mean blood concentration of FK506 of quadruple therapy group was significantly lower than dual therapy group(P=0.015) and triple therapy group(P=0.042) in first month postoperatively; In second and third months postoperatively, the mean blood concentration of FK506 of quadruple therapy group was significantly lower than dual therapy group(p=0.002), triple therapy group was significantly lower than dual therapy group(p=0.005), triple therapy group and quadruple therapy group were no significantly different; from fourth to sixth months postoperatively, the mean blood concentration of FK506 were no significantly different among three groups. In 6 months postoperatively, the frequencies of acute rejection was 25.9% for the dual therapy group, 11.1% for the triple therapy group , 7.5% for the quadruple therapy group; the frequencies of the quadruple therapy group was significantly lower than the dual therapy group(p=0.038); other groups were all no significantly different. The recipient and graft survival rate at 6-month were not different. The occurrence of hypertension, glycemia, tremor and infection were not significantly different in 6 months postoperatively. At 3-month postoperatively, ALT and serum cholesterin were significantly higher level of dual therapy group than quadruple therapy group(PALT=0.011, PTch=0.002). Platelet of triple and quadruple therapy groups was significantly lower than dual at 1-month postoperatively (P3-2=0.043, P4.2=0.006). Other indexes of assay were no significantly different among three groups at any time.Comparing QH group versus QL group as below: The recipient and graft survival rate at 6-month were not different. In 6 months postoperatively, the frequencies of acute rejection was 15.6% for QH group and 0% for QL group(p=0.156); the occurrence of hypertension, glycemia, and infection were notsignificantly different ; the occurrence of tremor of QL group was less than QH group(p=0.024).The serum creatinine(Cr) was significantly lower in QL group than QH group at fifteenth day and 3-month postoperatively(P15d=0.042,P3M= 0.019); The serum cholesterin was significantly lower level in QL group than QH group at 3-month and 6-month postoperatively (P3M=0.024, P6M=0.042). Other indexes of assay were no significantly different between two groups at any time.Conclusions1, Tacrolimus-based immunosuppressions (dual, triple, quadruple) are alleffectively and safely to prevent the acute rejection post-liver transplantation.Quadruple therapy was the best effectively and safely, and triple therapy wasbetter than dual therapy. 2, Quadruple therapy with lower blood concentration of FK506 was the bestregimen, it did not increase the...