Faculty Collaboration Database

Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression. Am J Transplant 2025 May;25(5):1045-1058

Date

12/21/2024

Pubmed ID

39706366

DOI

10.1016/j.ajt.2024.12.002

Scopus ID

2-s2.0-85214446802 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

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.

Author List

Vionnet J, Torres-Yaguana J, Miquel R, Abraldes JG, Wall J, Kodela E, Lozano JJ, Ruiz P, Navasa M, Marshall A, Nevens F, Gelson W, Leithead J, Masson S, Jaeckel E, Taubert R, Tachtatzis P, Eurich D, Simpson KJ, Bonaccorsi-Riani E, Ferguson J, Quaglia A, Demetris AJ, Lesniak AJ, Elstad M, Delord M, Douiri A, Rebollo-Mesa I, Martinez-Llordella M, Silva JAF, Markmann JF, Sánchez-Fueyo A

Author

Phaedra Tachtatzis MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Biomarkers
Female
Follow-Up Studies
Graft Rejection
Graft Survival
Humans
Immunosuppressive Agents
Liver
Liver Transplantation
Male
Middle Aged
Prognosis
Prospective Studies
Transplant Recipients
Transplantation Tolerance