Protocol for an international multicenter, prospective, observational, non-competitive, study to validate and optimise prediction models of 90-day and 1-year allograft failure after liver transplantation: The global IMPROVEMENT Study.

Abstract

More liver transplants (LT) are performed worldwide thanks to extended criteria donors (ECD). This is paralleled by a supposed increased risk of allograft failure (AF) at 90 and 365 days. This study has been designed to portray the LT practice worldwide and investigate models of AF prediction and the impact of risk mitigation strategies for further improving graft and patient outcomes. This is a multicenter, international, non-competitive, observational two segment study on consecutive LTs over two periods (2017-2019 and 2022-2024). A steering committee of LT experts defined the study protocol. The prospective segment will enroll 750 patients from 15 high-volume LT centers (50 per center), and the retrospective segment will enrol 4200 patients from 56 LT centers (75 per center). To provide a snapshot of the LT activity globally and to develop new algorithms for the timely prediction of AF at 90 and 365 days post-LT. The study also aims (1) to validate the existing predictive models and (2) to investigate the best time for re-transplantation, paying attention to the differences in AF and Ischemic cholangiopathy according to the donor types and mitigation strategies implemented in the various settings. Since the adoption of machine perfusion has increased in different proportions worldwide, models will be adjusted according to this parameter. Finally, retrospective and prospective data will be available for further stratifications and modelling according to the degree of decompensation at transplant, gender match, postoperative complications and their management. This protocol was approved by Fondazione Policlinico Universitario Agostino Gemelli IRCCS Ethics Committee (study ID: 4571) and the Institutional Review Board of the University of California, Los Angeles. The provisional study protocol was submitted to the main scientific international societies in the transplant field. Results will be published in international peer-reviewed journals and presented at congresses.