Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression

TY - JOUR

T1 - Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression

AU - Vionnet, Julien

AU - Torres-Yaguana, Jorge

AU - Miquel, Rosa

AU - Abraldes, Juan G

AU - Wall, Jurate

AU - Kodela, Elisavet

AU - Lozano, Juan-Jose

AU - Ruiz, Pablo

AU - Navasa, Miguel

AU - Marshall, Aileen

AU - Nevens, Frederik

AU - Gelson, Will

AU - Leithead, Joanna

AU - Masson, Steven

AU - Jaeckel, Elmar

AU - Taubert, Richard

AU - Tachtatzis, Phaedra

AU - Eurich, Dennis

AU - Simpson, Kenneth J

AU - Bonaccorsi-Riani, Eliano

AU - Ferguson, James

AU - Quaglia, Alberto

AU - Demetris, Anthony J

AU - Lesniak, Andrew J

AU - Elstad, Maria

AU - Delord, Marc

AU - Douiri, Abdel

AU - Rebollo-Mesa, Irene

AU - Martinez-Llordella, Marc

AU - Silva, Juliete A F

AU - Markmann, James F

AU - Sánchez-Fueyo, Alberto

N1 - Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2025/5

Y1 - 2025/5

N2 - The maintenance of stable allograft status in the absence of immunosuppression (IS), known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multicenter, biomarker-strategy design, IS withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver tissue collected before initiating IS weaning. One hundred sixteen adult stable liver transplant recipients were randomized 1:1 to either arm A (IS withdrawal regardless of biomarker status) or arm B (IS withdrawal in biomarker-positive recipients). Immunosuppression withdrawal was initiated in 82 participants, rejection occurred in 54 (67.5%), and successful discontinuation of IS was achieved in 22 (27.5%), but only 13 (16.3%) met operational tolerance histologic criteria (10 in arm A; 3 in arm B). The biomarker test did not yield useful information in selecting patients able to successfully discontinue IS. Operational tolerance was associated with time posttransplant, recipient age, presence of circulating exhausted CD8 + T cells, and a reduced number of immune synapses within the graft.

AB - The maintenance of stable allograft status in the absence of immunosuppression (IS), known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multicenter, biomarker-strategy design, IS withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver tissue collected before initiating IS weaning. One hundred sixteen adult stable liver transplant recipients were randomized 1:1 to either arm A (IS withdrawal regardless of biomarker status) or arm B (IS withdrawal in biomarker-positive recipients). Immunosuppression withdrawal was initiated in 82 participants, rejection occurred in 54 (67.5%), and successful discontinuation of IS was achieved in 22 (27.5%), but only 13 (16.3%) met operational tolerance histologic criteria (10 in arm A; 3 in arm B). The biomarker test did not yield useful information in selecting patients able to successfully discontinue IS. Operational tolerance was associated with time posttransplant, recipient age, presence of circulating exhausted CD8 + T cells, and a reduced number of immune synapses within the graft.

UR - https://www.scopus.com/pages/publications/85214446802

U2 - 10.1016/j.ajt.2024.12.002

DO - 10.1016/j.ajt.2024.12.002

M3 - Article

C2 - 39706366

SN - 1600-6135

VL - 25

JO - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

JF - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

IS - 5

M1 - 1045-1058

ER -