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

Vionnet, Julien;Torres-Yaguana, Jorge;Miquel, Rosa;Abraldes, Juan G;Sánchez-Fueyo, Alberto;et.al.
(2025) American Journal of Transplantation — Vol. 25, n° 5, p. 1045-1058 (2025)

Files

Vionnet_2024.pdf
  • Open Access
  • Adobe PDF
  • 2.05 MB
  • https://creativecommons.org/licenses/by/4.0/
Download

Details

Authors
  • Vionnet, JulienInstitute of Liver Studies, School of Immunology and Microbial Sciences, King's College London University and King's College Hospital, London, UK/a
    Author
  • Torres-Yaguana, JorgeInstitute of Liver Studies, School of Immunology and Microbial Sciences, King's College London University and King's College Hospital, London, UK/
    Author
  • Miquel, RosaInstitute of Liver Studies, School of Immunology and Microbial Sciences, King's College London University and King's College Hospital, London, UK/
    Author
  • Abraldes, Juan GLiver Unit, Division of Gastroenterology, University of Alberta, Edmonton, Canada
    Author
  • Bonaccorsi Riani, ElianoUCLouvain
    Author
  • Sánchez-Fueyo, AlbertoInstitute of Liver Studies, School of Immunology and Microbial Sciences, King's College London University and King's College Hospital, London, UK
    Author
Show more
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.
Affiliations

Citations

  • APA
  • Chicago
  • FWB

Vionnet, J., Torres-Yaguana, J., Miquel, R., Abraldes, J. G., Wall, J., Kodela, E., Lozano, J.-J., Ruiz, P., Navasa, M., Marshall, A., Nevens, F., Gelson, W., Leithead, J., Masson, S., Jaeckel, E., Taubert, R., Tachtatzis, P., Eurich, D., Simpson, K. J., et al. (2025). Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression. American Journal of Transplantation, 25(5), 1045-1058. https://doi.org/10.1016/j.ajt.2024.12.002 (Original work published 2025)