PMID- 19092340
OWN - NLM
STAT- MEDLINE
DCOM- 20090113
LR  - 20131121
IS  - 1528-1140 (Electronic)
IS  - 0003-4932 (Linking)
VI  - 248
IP  - 6
DP  - 2008 Dec
TI  - Tacrolimus monotherapy in liver transplantation: one-year results of a 
      prospective, randomized, double-blind, placebo-controlled study.
PG  - 956-67
LID - 10.1097/SLA.0b013e31819009c9 [doi]
AB  - BACKGROUND: Minimal immunosuppression (IS) is desirable in organ transplantation 
      to reduce side effects and to promote the process of tolerance induction. 
      MATERIAL AND 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). CONCLUSION: 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.
FAU - Lerut, Jan
AU  - Lerut J
AD  - Department of Abdominal and Transplantation Surgery-Unit of Abdominal 
      Transplantation, Universite Catholique de Louvain Cliniques Universitaires 
      Saint-Luc, Brussels, Belgium. jan.lerut@uclouvain.be
FAU - Mathys, Jules
AU  - Mathys J
FAU - Verbaandert, Catherine
AU  - Verbaandert C
FAU - Talpe, Stephanie
AU  - Talpe S
FAU - Ciccarelli, Olga
AU  - Ciccarelli O
FAU - Lemaire, Julien
AU  - Lemaire J
FAU - Bonaccorsi-Riani, Eliano
AU  - Bonaccorsi-Riani E
FAU - Vanthuyne, Vincent
AU  - Vanthuyne V
FAU - Hetsch, Nathalie
AU  - Hetsch N
FAU - Roggen, Francine
AU  - Roggen F
FAU - Reyck, Chantal D E
AU  - Reyck CD
FAU - Goffette, Pierre
AU  - Goffette P
FAU - Latinne, Dominique
AU  - Latinne D
FAU - Orlando, Giuseppe
AU  - Orlando G
FAU - Rahier, Jacques
AU  - Rahier J
FAU - Sempoux, Christine
AU  - Sempoux C
FAU - Wallemacq, Pierre
AU  - Wallemacq P
FAU - Laterre, Pierre-Francois
AU  - Laterre PF
FAU - Gianello, Pierre
AU  - Gianello P
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Surg
JT  - Annals of surgery
JID - 0372354
RN  - 0 (Immunosuppressive Agents)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cholestasis, Intrahepatic/surgery
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Liver Cirrhosis/surgery
MH  - Liver Function Tests
MH  - *Liver Transplantation/immunology/mortality
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Tacrolimus/*therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2008/12/19 09:00
MHDA- 2009/01/14 09:00
CRDT- 2008/12/19 09:00
PHST- 2008/12/19 09:00 [entrez]
PHST- 2008/12/19 09:00 [pubmed]
PHST- 2009/01/14 09:00 [medline]
AID - 00000658-200812000-00008 [pii]
AID - 10.1097/SLA.0b013e31819009c9 [doi]
PST - ppublish
SO  - Ann Surg. 2008 Dec;248(6):956-67. doi: 10.1097/SLA.0b013e31819009c9.