Lerut Jan, Mathys Jules, Verbaandert Catherine, Talpe Stéphanie, Ciccarelli Olga, Lemaire Julien, Bonaccorsi-Riani Eliano, Vanthuyne Vincent, Hetsch Nathalie, Roggen Francine, Reyck Chantal D E, Goffette Pierre, Latinne Dominique, Orlando Giuseppe, Rahier Jacques, Sempoux Christine, Wallemacq Pierre, Laterre Pierre-François, Gianello Pierre
Department of Abdominal and Transplantation Surgery-Unit of Abdominal Transplantation, Université Catholique de Louvain Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Ann Surg. 2008 Dec;248(6):956-67. doi: 10.1097/SLA.0b013e31819009c9.
Minimal immunosuppression (IS) is desirable in organ transplantation to reduce side effects and to promote the process of tolerance induction.
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).
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).
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.
在器官移植中，理想的情况是采用最小化免疫抑制（IS），以减少副作用并促进耐受诱导过程。
2000年2月至2004年9月期间，156名接受初次肝移植的成年人（>15岁）被纳入一项前瞻性、随机、双盲、安慰剂对照、研究者主导的单中心研究，比较他克莫司（TAC）-安慰剂（PL）和TAC-低剂量、短期（64天）类固醇（ST）免疫抑制方案。随机分组时没有排除标准。所有患者均接受了12个月的随访（范围为12 - 84个月）。
TAC-PL组3个月和12个月的患者生存率分别为93.6%和87.2%，TAC-ST组分别为98.7%和94.7%（P分别为0.096和0.093）。3个月和12个月的移植物生存率分别为92.3%和85.9%，对比TAC-ST组的97.4%和92.3%（P分别为0.14和0.13）。在3个月和12个月时，TAC-PL组有20.5%（16例患者）和23%（18例患者）接受了抗排斥治疗；TAC-ST组分别为12.7%（10例患者）和20.5%（16例患者）接受了抗排斥治疗（P分别为0.20和0.54）。TAC-PL组3个月和12个月时皮质类固醇抵抗性排斥反应（CRR）的发生率为12.8%（10例患者），TAC-ST组为3.8%（3例患者）（P = 0.04）。在考虑145例未接受人工器官支持的移植患者时（n = 145），TAC-PL组中3个月和12个月时CRR的发生率为8.8%（6/68例患者），TAC-ST组为3.9%（3/77例患者）（P = 0.22）。TAC-PL组有1例（1.2%）患者被诊断为消失胆管综合征，TAC-ST组有4例（5.1%）患者（P = 0.17）。到1年时，TAC-PL组78.2%（61/78）的患者和TAC-ST组82%（64/78）的患者采用TAC单药治疗（P = 0.54）。在考虑67例TAC-PL组和74例TAC-ST组的存活患者时，单药治疗率分别为91%（61例患者）和86.5%（64例患者）（P = 0.39）。在1年时，TAC-PL组存活患者中有62.5%（42例患者）、TAC-ST组存活患者中有
