Clinical significance of the cellular pharmacodynamics of tacrolimus in living-donor liver transplantation.
Successful immunosuppressive therapy is critical for liver transplantation; however, a considerable number of patients experience fatal rejection or alternatively exhibit serious infection resulting from excessive immunosuppression. The in vitro tacrolimus response of peripheral blood mononuclear cells (PBMCs) before transplantation was compared to the clinical outcome up to 4 weeks after operation in 28 living-donor liver transplant recipients treated with tacrolimus. The tacrolimus IC(50) values against concanavalin A-induced PBMC blastogenesis in vitro were calculated. These recipients were classified into two groups with the mean tacrolimus IC(50) (0.18 ng/ml) as the cutoff point, after which the clinical outcome between the patient groups was compared. The allograft rejection incidence in the low-sensitivity group (IC(50) < 0.18 ng/ml; n = 16) was 6/12 (50.0%), which was significantly higher than the incidence of 2/16 (12.5%) in the high-sensitivity group (IC(50) > 0.18 ng/ml; n = 12) (p = 0.0297). In contrast, the infection incidence in the high-sensitivity group was 6/16 (37.5%), which was significantly higher than that of the low-sensitivity group (1/12; 8.3%) (p = 0.0401). These data suggest that patients exhibiting a low PBMC sensitivity to tacrolimus have a risk of rejection, whereas highly sensitive patients have a risk of infection in living-donor liver transplantations under tacrolimus therapy.
Department of 5th Surgery, Hachioji Medical Center, Tokyo Medical University, Tokyo 193-0944, Japan.
Abuduxukuer
A
Mijiti
Naoto
N
Matsuno
Hironori
H
Takeuchi
Sakae
S
Unezaki
Takeshi
T
Nagao
Toshihiko
T
Hirano
D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016031:Liver Transplantation; D019520:Living Donors; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016559:Tacrolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016559:Tacrolimus