Liver Transplantation in the Context of Acute-On-Chronic Liver Failure (ACLF): Where Do We Stand in 2025?

Abstract

Acute-on-chronic liver failure (ACLF) is a critical condition that arises in the context of advanced liver disease, marked by rapid liver function deterioration and associated multi-organ failure. This syndrome is associated with a major short-term mortality risk, requiring aggressive and specialized clinical care. Despite ongoing efforts, effective therapeutic options for ACLF are lacking, with liver transplantation (LT) considered the only life-saving intervention, yielding acceptable outcomes in carefully selected patients. However, the place of LT for ACLF remains a matter of debate, given the high prevalence of the syndrome, the sickness of liver transplant candidates, the persistent shortage of available liver grafts, and the increasing number of indications to LT. This review aims to provide a comprehensive analysis of the role of LT in ACLF, evaluating current evidence on patient selection, optimal timing for transplantation, and ongoing debates surrounding this practice, specifically the rationale for prioritizing graft allocation for this indication. Furthermore, we will explore global management strategies for ACLF, focusing on bridging patients to LT and improving survival outcomes. Through this review, we seek to enhance understanding of the evolving role of LT in ACLF and offer insights into future directions for clinical practice and research in this critical area.

Keywords: acute-on-chronic liver failure (ACLF); cirrhosis; liver transplantation; liver transplantation window; organ failure.

FIGURE 1

Concept of the “transplantation window” during a critical care hospitalization in severe ACLF with different scenari. (A) Rapid improvement of severe ACLF: patients must be referred to a LT center for evaluation as 1-year transplant-free survival is between 20% and 60%. (B) One transplantation window. (C) Two transplantation windows. The first “transplantation window” is likely more favorable (“greener”) than the second, as the patient presents with fewer complications related to hospitalization (e.g., deconditioning, colonization by multidrug-resistant bacteria, etc.). (D) Absence of transplantation window commonly due to uncontrolled sepsis and organ failure. Adapted from Artru, Trovato et al., Lancet Gastroenterol. Hepatol. 2024. [64].

FIGURE 2

Proposal for a management algorithm for a cirrhotic patient with severe ACLF and potential eligibility for liver transplantation (LT). Abbreviations: ACLF, Acute-on-chronic liver failure; CI, contraindication; LT, liver transplantation; SALT-M, Sundaram ACLF Liver Transplantation Mortality; TAM, Transplantation for ACLF-3 model Adapted from Artru, Trovato et al., Lancet Gastroenterol. Hepatol. 2024 [64].

FIGURE 3

Key unmet needs and future directions in liver transplantation for ACLF. Summary of four priority areas to improve LT outcomes in ACLF: (1) restoring equity via adapted allocation policies; (2) refining prediction models by integrating comorbidities, OF profiles, and graft quality; (3) standardizing pre-LT evaluation; and (4) optimizing peri-transplant management, including bridging strategies, ECLS use, and mitigation of infectious and CV risks. Abbreviations: ACLF, acute-on-chronic liver failure; LT, liver transplantation; OF, organ failure; ECLS, extracorporeal liver support; CV, cardiovascular.