Tacrolimus and single intraoperative high-dose of anti-T-lymphocyte globulins versus tacrolimus monotherapy in adult liver transplantation one-year results of an investigator-driven randomized controlled trial

Objective: 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). Background: The efficacy of ALS induction remains inconclusive in LT, because of poorly designed trials. Methods: A randomized controlled trial was conducted, including 206 adults (>15 years) and comparing tacrolimus monotherapy (TAC, n ¼ 109) and tacrolimus plus a single, intraoperative, high-dose (9 mg/kg), rabbit anti-T-lymphocyte globulins (ATLG; n ¼ 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. Results: At 1 year, 79/81 (96.3%) ATLG and 101/102 (99.0%) TAC patients were steroid-free (P ¼ 0.585); 28 (34.6%) ATLG, and 31 (30.4%) TAC patients were on double-drug immunosuppression (P ¼ 0.633). One-year PS and GS of ATLG and TAC patients were 84% and 92% (P ¼ 0.260) and 76% and 90% (P ¼ 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 ¼ 0.019), cumulative proportion of patients experiencing steroid-sensitive (11.3% ATLG vs 14.7% TAC, P ¼ 0.539), steroid-resistant (2.1% ATLG vs 3.7% TAC, P ¼ 0.686) and chronic rejection (1.0% ATLG vs 0.9% TAC, P ¼ 1.000) were similar. ATLG administration brought about greater hemodynamic instability and blood products use (P ¼ 0.001). Conclusions: 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.