OPTIMAL Primary Paper Published

The ITN trial, “Evaluation of Donor Specific Immune Senescence and Exhaustion as Biomarkers of Tolerance Post Liver Transplantation” (OPTIMAL) investigated the potential of donor-specific immune senescence as a biomarker for operational tolerance in liver transplant recipients, the results were published online in the American Journal of Transplantation in November 2024.

The trial was a prospective, multicenter study of 61 adult liver transplant recipients who were at least 3 years post-transplant. The primary endpoint was operational tolerance at 52 weeks following complete immunosuppression withdrawal (ISW). Only 16.4% of histologically and clinically stable long-term liver transplant recipients could successfully discontinue and remain off immunosuppression. Increased frequency of donor-specific T cell senescence, C4d deposition, and higher density of immune synapses on the screening liver biopsy emerged as potential candidate biomarkers for operational tolerance. The results of this study highlight the need for additional interventions to augment the low rate of spontaneous tolerance and further research to identify robust predictors of tolerance.