title: Tacrolimus monotherapy in liver transplantation: one-year results of a prospective, randomized, double-blind, placebo-controlled study.
abstract: 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.
authors.affiliation: Department of Abdominal and Transplantation Surgery-Unit of Abdominal Transplantation, Université Catholique de Louvain Cliniques Universitaires Saint-Luc, Brussels, Belgium. jan.lerut@uclouvain.be
authors.forename: Jan
authors.initials: J
authors.lastname: Lerut
authors.forename: Jules
authors.initials: J
authors.lastname: Mathys
authors.forename: Catherine
authors.initials: C
authors.lastname: Verbaandert
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Talpe
authors.forename: Olga
authors.initials: O
authors.lastname: Ciccarelli
authors.forename: Julien
authors.initials: J
authors.lastname: Lemaire
authors.forename: Eliano
authors.initials: E
authors.lastname: Bonaccorsi-Riani
authors.forename: Vincent
authors.initials: V
authors.lastname: Vanthuyne
authors.forename: Nathalie
authors.initials: N
authors.lastname: Hetsch
authors.forename: Francine
authors.initials: F
authors.lastname: Roggen
authors.forename: Chantal D E
authors.initials: CD
authors.lastname: Reyck
authors.forename: Pierre
authors.initials: P
authors.lastname: Goffette
authors.forename: Dominique
authors.initials: D
authors.lastname: Latinne
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Orlando
authors.forename: Jacques
authors.initials: J
authors.lastname: Rahier
authors.forename: Christine
authors.initials: C
authors.lastname: Sempoux
authors.forename: Pierre
authors.initials: P
authors.lastname: Wallemacq
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Laterre
authors.forename: Pierre
authors.initials: P
authors.lastname: Gianello
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus