The Significance of Whole Blood Tacrolimus Level on the Development of Acute Rejection in Liver Transplantation

Lee, Ung Hee; Lee, Min Ku; Suh, Kyung Suk; Lee, Kuhn Uk

Abstract

PURPOSE: Tacrolimus has been widely used to prevent acute rejection in liver transplantation and it requires drug concentration monitoring due to narrow therapeutic index. The aim of this study is to define an adequate whole blood tacrolimus level to prevent acute rejection and drug toxicity in early postoperative days.
METHODS
We reviewed 27 patients who underwent liver transplantation from November 1998 to January 2000 at the Department of Surgery, Seoul National University, College of Medicine. Tacrolimus plus steroid were used as initial immunosuppressive drugs. The trough whole blood tacrolimus level had been checked everyday from 2 days after transplantation by microparticle enzyme immunoassay (IMX Tacrolimus II assay). Acute rejection was confirmed by liver biopsy. We divided the patients into low level group (below median, n=13) and high level group (above median, n=14) according to average tacrolimus level within 30 days after transplantation. We compared the incidence of side effects between two groups. The average whole blood tacrolimus levels of the patients according to development of acute rejection were compared. The ratio of sex, age, donor status were also compared.
RESULTS
17 patients (63.0%) showed acute rejection within 30 days after transplantation. The median tacrolimus level of all patients within 30 days after transplantation was 11.39 ng/ml. The incidence of acute rejection in low level group (84.6%) was significantly higher than in high level group (42.9%) (P=0.046). The incidence of side effects between two groups was not different. Mean tacrolimus level of the patients without acute rejection within 30 days after transplantation (12.43+/-1.78 ng/ml) was significantly higher than that of the patients with acute rejection (10.81+/-1.17 ng/ml) (P=0.022). Daily average levels were different statistically on 7th (18.4+/-6.7 vs 10.7+/-3.3 ng/ml, P=0.009), 8th (16.0+/-6.7 vs 11.0+/-3.1 ng/ml, P=0.016), 23th (12.2+/-4.5 vs 9.0+/-2.5 ng/ml, P=0.030), 24th (13.7+/-3.2 vs 9.5+/-2.5 ng/ml, P= 0.009), 25th (13.5+/-3.0 vs 8.9+/-4.0 ng/ml, P=0.009) days after transplantation. Sex, age (adult or child) and donor status (living or cadevaric) didn't affect the development of acute rejection.
CONCLUSION
The whole blood tacrolimus level should be kept near 15 ng/ml around 7 and 8 days after transplantation to prevent acute rejection in liver transplantation.