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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

Iesari, Samuele, MD*,†; Ackenine, Kevin, MD*; Foguenne, Maxime, MD*; De Reyck, Chantal, RN, CCTC*; Komuta, Mina, MD, PhD§; Bonaccorsi Riani, Eliano, MD*; Ciccarelli, Olga, MD*; Coubeau, Laurent, MD*; Lai, Quirino, MD, PhD; Gianello, Pierre, MD, PhD; Lerut, Jan, MD, PhD, FACS*

doi: 10.1097/SLA.0000000000002943
ESA-RANDOMIZED CONTROLLED TRIALS

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 = 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.

Results: 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).

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.

*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

Department of General Surgery and Organ Transplantation, La Sapienza University, Rome, Italy

§Department of Pathology, University Hospitals Saint-Luc, Université Catholique de Louvain, Brussels, Belgium

Laboratory of Experimental Surgery and Transplantation, Université Catholique de Louvain, Brussels, Belgium.

Reprints: Jan Lerut, MD, PhD, FACS, Starzl Abdominal Transplant Unit, University Hospitals Saint-Luc, Université Catholique de Louvain, Avenue Hippocrates 10, 1200 Brussels, Belgium. E-mail: jan.lerut@uclouvain.be.

Disclosure: Neovii Biotech GmbH (Gräfelfing, Germany) provided an unrestricted grant for immunologic research related to lymphocytic subpopulation typing and cytokines profiling (Data not shown in this report). SI is recipient of the Hepatotransplant and Euroliver Foundation grants, attributed for research in immunosuppression handling in adult liver transplantation.

The authors declare no conflicts of interest.

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