Starzl Abdominal Transplant Unit, University Hospitals Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Ann Surg. 2018 Nov;268(5):776-783. doi: 10.1097/SLA.0000000000002943.
The aim of the study is to evaluate whether intra-operative induction with anti-lymphocytic serum (ALS) is superior to no induction in adult liver transplantation (LT).
The efficacy of ALS induction remains inconclusive in LT, because of poorly designed trials.
A randomized controlled trial was conducted, including 206 adults (>15 years) and comparing tacrolimus monotherapy (TAC, n = 109) and tacrolimus plus a single, intraoperative, high-dose (9 mg/kg), rabbit anti-T-lymphocyte globulins (ATLG; n = 97). All patients had similar follow-up, including Banff-scored biopsies. Rejection was considered clinically relevant and treated if pathologic and biochemical changes were concordant. The primary endpoint was immunosuppression minimization to monotherapy; secondary endpoints were biopsy-proven rejection, clinical rejection, patient (PS) and graft (GS) survival.
At 1 year, 79/81 (96.3%) ATLG and 101/102 (99.0%) TAC patients were steroid-free (P = 0.585); 28 (34.6%) ATLG, and 31 (30.4%) TAC patients were on double-drug immunosuppression (P = 0.633). One-year PS and GS of ATLG and TAC patients were 84% and 92% (P = 0.260) and 76% and 90% (P = 0.054).Despite significantly a fewer day-7 moderate-to-severe acute cellular rejections (ACR) in ATLG group (10.0% vs 24.0% in TAC group, P = 0.019), cumulative proportion of patients experiencing steroid-sensitive (11.3% ATLG vs 14.7% TAC, P = 0.539), steroid-resistant (2.1% ATLG vs 3.7% TAC, P = 0.686) and chronic rejection (1.0% ATLG vs 0.9% TAC, P = 1.000) were similar. ATLG administration brought about greater hemodynamic instability and blood products use (P = 0.001).
At 1 year from LT, ATLG induction did not significantly affect immunosuppressive load, treated rejection, patient, and graft survival. The observed adverse events justify a modification of dosing and timing of ATLG infusion. Long-term results are required to judge the ATLG possible benefits on immunosuppressive load and tolerance induction.
本研究旨在评估成人肝移植术中应用抗淋巴细胞血清（ALS）诱导是否优于无诱导。
由于试验设计不佳，ALS 诱导在肝移植中的疗效仍不确定。
进行了一项随机对照试验，纳入 206 例（>15 岁）成人，并比较了他克莫司单药治疗（TAC，n=109）和他克莫司联合术中单次高剂量（9mg/kg）兔抗 T 淋巴细胞球蛋白（ATLG；n=97）。所有患者均接受了类似的随访，包括 Banff 评分活检。如果病理和生化改变一致，则认为排斥反应具有临床相关性并进行治疗。主要终点是免疫抑制最小化至单药治疗；次要终点是活检证实的排斥反应、临床排斥反应、患者（PS）和移植物（GS）存活率。
在 1 年时，81/81（96.3%）例 ATLG 和 102/102（99.0%）例 TAC 患者均无需使用类固醇（P=0.585）；28 例（34.6%）ATLG 和 31 例（30.4%）TAC 患者接受了双重免疫抑制治疗（P=0.633）。ATLG 和 TAC 患者的 1 年 PS 和 GS 分别为 84%和 92%（P=0.260）和 76%和 90%（P=0.054）。尽管 ATLG 组第 7 天中重度急性细胞排斥反应（ACR）的发生率明显较低（10.0%比 TAC 组 24.0%，P=0.019），但经历类固醇敏感（11.3%ATLG 比 14.7%TAC，P=0.539）、类固醇耐药（2.1%ATLG 比 3.7%TAC，P=0.686）和慢性排斥反应（1.0%ATLG 比 0.9%TAC，P=1.000）的患者比例相似。ATLG 给药导致更大的血流动力学不稳定和血液制品使用（P=0.001）。
肝移植术后 1 年，ATLG 诱导并未显著影响免疫抑制负荷、治疗排斥反应、患者和移植物存活率。观察到的不良事件证明需要调整 ATLG 输注的剂量和时间。需要长期结果来判断 ATLG 在免疫抑制负荷和诱导耐受方面的可能益处。
