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Modèles d'appariement du greffon à son hôte, gestion de file d'attente et évaluation du bénéfice de survie en transplantation hépatique à partir de la base nationale de l'Agence de la Biomédecine.

Abstract : Liver transplantation (LT) is the only life-saving procedure for liver failure. One of the major impediments to LT is the shortage of organs. To decrease organ shortage, donor selection criteria were expanded with the use of extended criteria donor (ECD). However, an unequivocal definition of these ECD livers was not available. To address this issue, an American Donor Risk Index (DRI) was developed to qualify those grafts. But to whom should those ECD grafts be given? Indeed, a proper use of ECD grafts could reduce organ shortage. The aim of this thesis is to establish a new graft allocation system which would allow each graft to be transplanted in the candidate whose LT will allow the greatest survival benefit; and to evaluate the matching between donors and recipients taking into account ECD grafts.The first step was the external validation of the DRI as well as the resultant Eurotransplant-DRI score. However, calibration and discrimination were not maintained on the French database. A new prognostic donor score: the DRI-Optimatch was then developed using a Cox donor model with adjustment on recipient covariates. The model was validated by bootstrapping with correction of the performance by the optimism.The second step was to explore the matching between donors and recipients in order to allocate ECD grafts optimally. Consideration should be given to the donor and recipient criteria, as assessed by the DRI-Optimatch and the Model for End-stage Liver Disease (MELD), respectively. The sequential stratification method retained is based on the randomized controlled trial principle. We then estimated, through hazard ratios, the survival benefit for different categories of MELD and DRI-Optimatch compared against the group of candidates remaining on the wait list (WL) and waiting for a transplant with a graft of better quality (lower DRI-Optimatch).In the third step, we have developed an allocation system based on survival benefit combining the two main principles in graft allocation; urgency and utility. In this system, a graft is allocated to the patient with the greatest difference between the predicted post-transplant life and the estimated waiting time for a specific donor. This model is mainly based on two Cox models: pre-LT and post-LT. In these two models the event of interest being the death of the patient, for the pre-graft model, the dependent censoring was taken into account. Indeed, on the WL, death is often censored by another event: transplantation. A method derived from Inverse Probability of Censoring Weighting was used to weight each observation. In addition, longitudinal data and survival data were also used. A partly conditional model, to estimate the effect of time-dependent covariates in the presence of dependent censoring, was therefore used for the pre-LT model.After developing a new allocation system, the fourth and final step was to evaluate it through Discrete Event Simulation (DES).
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Audrey Winter. Modèles d'appariement du greffon à son hôte, gestion de file d'attente et évaluation du bénéfice de survie en transplantation hépatique à partir de la base nationale de l'Agence de la Biomédecine.. Autres [stat.ML]. Université Montpellier, 2017. Français. ⟨NNT : 2017MONTS024⟩. ⟨tel-01917665⟩

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