Evaluation of a delayed liver transplantation strategy for patients with HCC receiving bridging therapy: the DELTA-HCC study.

BACKGROUND & AIMS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal ablation during the waiting phase. The DS involves postponing LT until recurrence. The purpose of this study was to evaluate the DS to make sure that it did not hamper pre- and post-LT outcomes. METHODS: Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to six groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. Kaplan-Meier estimates of the 18-month risk of dropout for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post-LT survival rates were compared. RESULTS: Median waiting-time in the DS group was 910 days. Pre-LT dropout probability was significantly lower in the DS group compared to other groups (13% vs. 19%, p = 0.0043) and significantly higher in the T1 group (25.4%, p = 0.05). Post-LT HCC recurrence rate in the multiple nodules group was significantly higher (19.6%, p = 0.019), while 5-year post-LT survival did not differ among groups and was 74% in the DS group (p = 0.22). CONCLUSION: The DELTA-HCC study shows that DS does not negatively impact either pre- nor post-LT patient outcomes, and has the potential to allow for redistribution of organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpectedly high risk of dropout in T1 patients seems related to the MELD-based offering rules underserving this subgroup. IMPACTS AND IMPLICATIONS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy was adopted in France in 2015. It involves postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA-HCC study was conducted to evaluate this nationwide strategy. It shows in a European LT program that delayed strategy does not negatively impact pre- nor post-LT patient outcomes and is relevant to up to 20% of LT candidates; thus, it could potentially enable the redistribution of organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpectedly high risk of dropout in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup.

Kidney Transplantation in Patients With AA Amyloidosis: Outcomes in a French Multicenter Cohort.

RATIONALE & OBJECTIVE: Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high rates of disease recurrence. However, the data are inconclusive and mostly based on studies from the early 2000s and earlier. STUDY DESIGN: Retrospective multicenter cohort study. SETTING & PARTICIPANTS: We searched the French national transplant database to identify all patients with renal AA amyloidosis who underwent kidney transplantation between 2008 and 2018. EXPOSURES: Age, cause of amyloidosis, use of biotherapies, and C-reactive protein levels. OUTCOMES: Outcomes were all-cause mortality and allograft loss. We also reported amyloidosis allograft recurrence, occurrence of acute rejection episodes, as well as infectious, cardiovascular, and neoplastic disease events. ANALYTICAL APPROACH: Kaplan-Meier estimator for mortality and cumulative incidence function method for allograft loss. Factors associated with patient and allograft survival were investigated using a Cox proportional hazards model and a cause-specific hazards model, respectively. RESULTS: 86 patients who received kidney transplants for AA amyloidosis at 26 French centers were included. The median age was 49.4 years (IQR, 39.7-61.1). The main cause of amyloidosis was familial Mediterranean fever (37 cases; 43%). 16 (18.6%) patients received biotherapy after transplantation. Patient survival rates were 94.0% (95% CI, 89.1-99.2) at 1 year and 85.5% (77.8-94.0) at 5 years after transplantation. Cumulative incidences of allograft loss were 10.5% (4.0-17.0) at 1 year and 13.0% (5.8-20.1) at 5 years after transplantation. Histologically proven AA amyloidosis recurrence occurred in 5 transplants (5.8%). An infection requiring hospitalization developed in 55.8% of cases, and there was a 27.9% incidence of acute allograft rejection. Multivariable analysis showed that C-reactive protein concentration at the time of transplantation was associated with patient survival (HR, 1.01; 95% CI, 1.00-1.02; P=0.01) and allograft survival (HR, 1.68; 95% CI, 1.10-2.57; P=0.02). LIMITATIONS: The study lacked a control group, and the effect of biotherapies on transplantation outcomes could not be explored. CONCLUSIONS: This relatively contemporary cohort of patients who received a kidney transplant for AA amyloidosis experienced favorable rates of survival and lower recurrence rates than previously reported. These data support the practice of treating these patients with kidney transplantation for end-stage kidney disease. PLAIN-LANGUAGE SUMMARY: AA amyloidosis is a severe and rare disease. Kidney involvement is frequent and leads to end-stage kidney disease. Because of the involvement of other organs, these patients are often frail, which has raised concerns about their suitability for kidney transplantation. We reviewed all patients with AA amyloidosis nephropathy who underwent kidney transplantation in France in the recent era (2008-2018) and found that the outcomes after kidney transplantation were favorable, with 85.5% of patients still alive 5 years after transplantation, a survival rate that is comparable to the outcomes of patients receiving a transplant for other forms of kidney diseases. Recurrence of amyloidosis in the transplanted kidney was infrequent (5.8%). These data support the practice of kidney transplantation for patients with AA amyloidosis who experience kidney failure.

Fate of discarded kidney transplants: experience of the transplant university hospital center of Rennes / Devenir des greffons rénaux refusés : expérience du centre de transplantation du CHU de Rennes

Introduction: In a context of tension on the number of available kidney transplants compared to the number needed, the practices of refusal of transplants in the Rennes transplantation center were evaluated. Materials and methods: The donors completely refused by our team (no kidney accepted for any Rennes recipient) between January 1st 2012 and December 31st 2015 were identified from the national CRISTAL registry. The outcome of these refused transplants (possible transplantation in another center), the data of the recipients (from Rennes and other centers) and the data of the donors (refused and then finally accepted) were extracted. The outcome of recipients (from Rennes and other centers) was compared: graft survival (censored on death) and patient survival (not censored on cessation of function). The Kidney Donor Profile Index (KDPI) score was calculated and its usefulness studied. Results: Among the 203 rejected donors, 172 (85 %) were accepted for transplantation in another center; 89% of these grafts were functional at one year. In univariate analysis, Rennes recipients transplanted after a refusal had a better graft survival (censored on death) than recipients transplanted in another center with the refused graft (p < 0.001). The main limitation of this analysis is the non-comparability of the groups. The KDPI score was significantly associated with graft survival (censored on death). Of the 151 Rennes patients who had a refusal, 3% were still on the waiting list at the end of the observation period, the others spent a median additional time on dialysis of 220 days (Q1-Q3 81-483). Conclusion: Rennes recipients transplanted after a first refusal seem to have a better graft survival (censored on death) than recipients from other centers transplanted with refused grafts. This is to be weighed against the additional time on dialysis and even the risk of non-transplantation.

Introduction: Dans un contexte de tension sur le nombre de greffons rénaux disponibles comparé au nombre nécessaire, les pratiques de refus des greffons du centre de transplantation rennais ont été évaluées. Matériels et méthodes: À partir du registre national CRISTAL, les donneurs complètement refusés par notre équipe (aucun rein accepté pour aucun receveur rennais) entre le 1er janvier 2012 et le 31 décembre 2015 ont été identifiés. Le devenir de ces greffons refusés (éventuelle greffe dans un autre centre), les données des receveurs (rennais et des autres centres) et les données des donneurs (refusés puis finalement acceptés) ont été extraits. Le devenir des receveurs (rennais et des autres centres) a été comparé : survie du greffon (censurée sur le décès) et du patient (non censurée sur l'arrêt de fonction). Le score KDPI (Kidney Donor Profile Index) a été calculé et son intérêt étudié. Résultats: Parmi les 203 donneurs refusés, 172 (85 %) ont permis une transplantation dans un autre centre, dont 89 % de greffons fonctionnels à un an. En analyse univariée, les receveurs rennais greffés après un refus avaient une meilleure survie greffon (censurée sur le décès) que les receveurs greffés dans un autre centre avec le greffon refusé (p < 0,001). La principale limite de cette analyse est la non-comparabilité des groupes. Le score KDPI était significativement associé à la survie greffon (censurée sur le décès). Parmi les 151 patients rennais qui ont eu un refus, 3 % étaient toujours sur liste d'attente à l'issue de la période d'observation, les autres passaient un temps médian supplémentaire en dialyse de 220 jours (Q1-Q3 81-483). Conclusion: Les receveurs rennais greffés après un premier refus semblent avoir une meilleure survie du greffon (censurée sur le décès) que les receveurs des autres centres greffés avec les greffons refusés. C'est à mettre en balance avec le temps supplémentaire en dialyse, voire le risque de non-greffe.