Liver transplantation for severe Acute-on-Chronic Liver Failure: Where do we stand?

Acute-on-Chronic Liver Failure (ACLF) occurs in the setting of chronic liver ­disease and is characterized by a combination of acute hepatic failure, extrahepatic organ dysfunction, and high short-term mortality. In the absence of specific treatment, liver transplantation (LT) is the only therapeutic option capable of modifying the prognosis for the most severe patients. These patients undergo transplantation in a challenging context, often hospitalized in critical care units with multiple organ failure. In recent years, several studies have reported favorable outcomes after liver transplantation in selected patients. Most of these data have been published since 2019, date of the last review on the subject, and show one-year survival rates often exceeding 80%. Some patient-dependent variables (age, diabetes, general condition), intensive care unit stay-related factors (evolution and type of organ failure, lactate levels, and transplantation window), and donor-related factors appear to be among the determinants of this favorable prognosis after transplantation. Alongside these findings, numerous questions and controversies arise from the study results and LT activity in this population: the robustness of registry-based studies, adherence to graft utility, disparities in access to LT, pre-transplant evaluation procedures, and the role of living donation. This updated review aims to comprehensively address all these questions and provide an comprehensive overview of LT for severe ACLF.