Tacrolimus monotherapy in liver transplantation: one-year results of a prospective, randomized, double-blind, placebo-controlled study.
BACKGROUND
Minimal immunosuppression (IS) is desirable in organ transplantation to reduce side effects and to promote the process of tolerance induction.


METHODS
Between February 2000 and September 2004, 156 adults (>15 years old) receiving a primary liver graft were enrolled in a prospective, randomized, double-blind, placebo-controlled, investigator-driven single-center study comparing tacrolimus (TAC)-placebo (PL) and TAC-low-dose, short-term (64 days) steroid (ST) IS. There were no exclusion criteria at moment of randomization. All patients had a 12-month follow-up (range, 12-84).


RESULTS
Three- and 12-month patient survival rates were 93.6% and 87.2% in the TAC-PL group and 98.7% and 94.7% in TAC-ST group (P = 0.096 and P = 0.093, respectively). Three- and 12-month graft survival rates were 92.3% and 85.9% versus 97.4% and 92.3% (P = 0.14 and 0.13, respectively). By 3 and 12 months, rejection treatment had been given in 20.5% (16 pts) and 23% (18 pts) of TAC-PL patients and in 12.7% (10 pts) and 20.5% (16 pts) of TAC-ST patients (P = 0.20 and 0.54). Corticosteroid-resistant rejection (CRR) at 3 and 12 months was recorded in 12.8% (10 pts) of TAC-PL patients and 3.8% (3 pts) of TAC-ST patients (P = 0.04). When considering the 145 patients transplanted without artificial organ support (n = 145), CRR at 3 and 12 months was recorded in 8.8% (6/68 pts) of TAC-PL patients and in 3.9% (3/77 pts) of TAC-ST patients (P = 0.22). Vanishing bile duct syndrome was diagnosed in 1 (1.2%) TAC-PL patient and 4 (5.1%) TAC-ST patients (P = 0.17). By 1 year, 78.2% (61/78) of TAC-PL patients and 82% (64/78) of TAC-ST patients were on TAC monotherapy (P = 0.54). When considering 67 TAC-PL and 74 TAC-ST survivors, rates of monotherapy were 91% (61 pts) and 86.5% (64 pts) (P = 0.39). At 1 year, 62.5% (42 pts) of TAC-PL survivors and 64.9% (48 pts) of TAC-ST survivors were on low-dosage (<6 ng/mL) TAC monotherapy (P 0.79).


CONCLUSIONS
TAC monotherapy can be achieved safely without compromising graft nor patient survival in a primary, even unselected, adult liver transplant population. The higher incidence of early CRR in the TAC-PL group related to the significantly higher number of patients transplanted while being on artificial organ support. In such condition, this monodrug immunosuppressive strategy needs to be adapted. TAC monotherapy strategy should lay the basis for further large scale minimization studies in liver transplantation.
Lerut
Jan
J
Department of Abdominal and Transplantation Surgery-Unit of Abdominal Transplantation, Université Catholique de Louvain Cliniques Universitaires Saint-Luc, Brussels, Belgium. jan.lerut@uclouvain.be
Mathys
Jules
J
Verbaandert
Catherine
C
Talpe
Stéphanie
S
Ciccarelli
Olga
O
Lemaire
Julien
J
Bonaccorsi-Riani
Eliano
E
Vanthuyne
Vincent
V
Hetsch
Nathalie
N
Roggen
Francine
F
Reyck
Chantal D E
CD
Goffette
Pierre
P
Latinne
Dominique
D
Orlando
Giuseppe
G
Rahier
Jacques
J
Sempoux
Christine
C
Wallemacq
Pierre
P
Laterre
Pierre-François
PF
Gianello
Pierre
P
D000328:Adult; D000368:Aged; D002780:Cholestasis, Intrahepatic / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000601:surgery; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D007166:Immunosuppressive Agents; D016559:Tacrolimus