François Faitot

La principale limite en chirurgie hépatobiliaire est représentée par l’insuffisance hépatocellulaire (IHC) posthépatectomie (Hx) ou la dysfonction du greffon (EAD) après transplantation (TH). Peu d’études ont évalué le métabolisme du foie dans son ensemble, du fait du manque de technique utilisable en clinique. La métabolomique HR-MAS-RMN pourrait pallier à ce manque. Le but de cette thèse était d’évaluer l’apport de cette technique en chirurgie hépatobiliaire.En TH (n=42), le profil métabolique (PM) prédisait le risque d’EAD et identifiait le lactate et la phosphocholine comme biomarqueurs permettant d’envisager un matching métabolique. Après Hx majeure (n=45), le PM prédisait la survenue d’un décès par IHC. Ce PM différait du profil cirrhotique en décompensation et était compatible avec celui de système cellulaire prolifératif. Une étude préliminaire montrait que le PM prédisait la récidive à 1 an après hépatectomie. Ce travail montre l’intérêt de la métabolomique par HR MAS RMN pour prédire l’issue d’une Hx ou d’une TH dans un temps compatible avec la clinique. Ces données orientent vers la piste de l’intervention métabolique en chirurgie hépatique.

INTRODUCTION: There is considerable debate over the indication of liver transplantation (LT) for critically ill patients with cirrhosis, in part due to their potentially poor post-LT prognosis. We analyzed the epidemiology and outcome of LT for critically ill patients with cirrhosis over 4 time periods of 4 years. METHODS: We included adult patients who underwent liver transplant alone between 2005 and 2020 using the United Network for Organ Sharing registry database. We defined critically ill patients with cirrhosis as being in the intensive care unit with 1 or more of the following characteristics at the time of LT: (i) grade III/IV hepatic encephalopathy, (ii) mechanical ventilation, (iii) dialysis, and (iv) vasopressors. RESULTS: A total of 85,594 LT recipients were included, 5,827 (6.8%) of whom were classified as being critically ill with cirrhosis at the time of LT. The number and percentage of critically ill LT recipients with cirrhosis increased over the study period: 819 (4.3%) in 2005–2008 vs 2,067 (7.9%) in 2017–2020, P < 0.001. There was a 17% absolute increase in 1-year survival after LT: 72.5% in 2005–2008 vs 89.5% in 2017–2020, P < 0.001. The 1-year post-LT survival gap between critically ill and noncritically ill patients with cirrhosis narrowed over the study period: 16.7 percentage points in 2005–2008 vs 4.6 percentage points in 2017–2020. The year of LT was independently associated with lower 1-year post-LT mortality (hazard ratio 0.92, 95% confidence interval 0.91–0.93, P < 0.001). DISCUSSION: The absolute number and relative percentage of LT recipients who were critically ill increased over time, as did 1-year post-LT survival. Meanwhile, the gap in survival between this group of patients and noncritically ill patients with cirrhosis decreased but persisted. Cautious access to selected LT candidates who are critically ill may be warranted, provided the gap in survival with noncritically ill patients remains as small as possible.

BackgroundIn recent years, age at liver transplantation (LT) has markedly increased. In the context of organ shortage, we investigated the impact of recipient age on post-transplantation mortality. MethodsAll adult patients who received a first LT between 2007 and 2017 were included in this cross-sectional study. Recipients' characteristics at the time of listing, donor and surgery data, post-operative complications and follow-up of vital status were retrieved from the national transplantation database. The impact of age on 5-year overall mortality post-LT was estimated using a flexible multivariable parametric model which was also used to estimate the association between age and 10-year net survival, accounting for expected age- and sex-related mortality. ResultsAmong the 7610 patients, 21.4% were aged 60-65 years, and 15.7% over 65. With increasing age, comorbidities increased but severity of liver disease decreased. Older recipient age was associated with decreased observed survival at 5 years after LT (p < .001), with a significant effect particularly during the first 2 years. The linear increase in the risk of death associated with age does not allow any definition of an age's threshold for LT (p = .832). Other covariates associated with an increased risk of 5-year death were dialysis and mechanical ventilation at transplant, transfusion during LT, hepatocellular carcinoma and donor age. Ten-year flexible net survival analysis confirmed these results. ConclusionAlthough there was a selection process for older recipients, increasing age at LT was associated with an increased risk of death, particularly in the first years after LT.