Long-term outcome following liver transplantation of patients with ACLF grade 3

• Published in: Journal of hepatology 2025-01, Vol.82 (1), p.62-71
• Main Authors: Artru, Florent, Sacleux, Sophie-Caroline, Ursic-Bedoya, Jose, Ntandja Wandji, Line Carole, Lutu, Alina, L’Hermite, Sebastien, Levy, Clementine, Khaldi, Marion, Levesque, Eric, Dharancy, Sebastien, Boleslawski, Emmanuel, Lebuffe, Gilles, Le Goffic, Charles, Ichai, Philippe, Coilly, Audrey, De Martin, Eleonora, Vibert, Eric, Meszaros, Magdalena, Herrerro, Astrid, Monet, Clement, Jaber, Samir, Samuel, Didier, Mathurin, Philippe, Labreuche, Julien, Pageaux, Georges-Philippe, Saliba, Faouzi, Louvet, Alexandre
• Format: Article
• Language: English
• Subjects: acute-on-chronic liver failure; Acute-On-Chronic Liver Failure - epidemiology; Acute-On-Chronic Liver Failure - etiology; Acute-On-Chronic Liver Failure - mortality; Acute-On-Chronic Liver Failure - surgery; Adult; Aged; Cause of Death; Charlson comorbidity index; Cirrhosis; Female; Follow-Up Studies; France - epidemiology; Graft Survival; Humans; intensive care; Life Sciences; liver transplantation; Liver Transplantation - adverse effects; Liver Transplantation - methods; major cardiovascular events; Male; Middle Aged; organ failure; Retrospective Studies; Severity of Illness Index; Survival Rate; Treatment Outcome
• ISSN: 0168-8278; 1600-0641; 1600-0641
• DOI: 10.1016/j.jhep.2024.06.039

Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on-chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included in a three-centre retrospective French study published in 2017. All patients with ACLF-3 (n = 73), as well as their transplanted matched controls with ACLF-2 (n = 145), 1 (n = 119) and no ACLF (n = 292), who participated in the Princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survival rates, causes of death and their predictive factors. Median follow-up of patients with ACLF-3 was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patient survival rates were 72.6% vs. 69.7% vs. 76.4% vs. 77.0%, respectively (p = 0.31). Ten-year patient survival for ACLF-3 was 56.8% and was not different to other groups (p = 0.37). Leading causes of death in patients with ACLF-3 were infections (33.3%) and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and CLIF-C ACLF score were independently associated with 10-year patient survival. Long-term graft survival rates were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years. 5- and 10-year patient and graft survival rates were not different in patients with ACLF-3 compared to matched controls. 5-year patient survival is higher than the 50%-70% threshold defining the utility of a liver graft. Efforts should focus on candidate selection based on comorbidities, as well as the prevention of infection and cardiovascular events. While short-term outcomes following liver transplantation in the most severely ill patients with cirrhosis (acute-on-chronic liver failure grade 3 [ACLF-3]) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favourable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in patients with ACLF-3 compared to matched patients with ACLF-2, ACLF-1, and no-ACLF. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidity evaluation, such as the age-adjusted Charlson com