With the rising prevalence of chronic liver disease worldwide, the incidence and prevalence of acute-on-chronic liver failure (ACLF) are increasing and attribute to higher morbidity, mortality, and healthcare costs. Many of such patients die without being considered for the lifesaving treatment option of liver transplantation. The underutilization of liver transplantation as a therapeutic option in the setting of ACLF, is due to multiple reasons; with the heterogeneity of ACLF and the lack of universal definition being the key players. Liver transplantation listing and allocation are based on MELD score. As of now, we do not know where MELD score stands in regard to defining ACLF and the prognostication of such patients. This insight is very important for the efficient identification of potential liver transplantation candidates in the setting of ACLF. This review paper investigates the role of liver transplantation in the setting of ACLF. In light of recent evidence, MELD score is not the perfect model in the setting of ACLF either. The safety of liver transplantation, either deceased donor or living donor, among ACLF patients has been debated. The short-term mortality rate of ACLF patients has created a need for a standard liver transplant selection criterion for these patients. Based on published literature, we find that three commonly used ACLF definitions may be used in combination to define the sensitivity, specificity, and futility of ACLF and we propose an algorithm to best identify patients for urgent liver transplantation in the setting of ACLF. Moreover, we discuss the data on the safety of liver transplantation in the setting of ACLF. Future validation of this multifaceted approach could bridge the gap between ACLF patients and appropriately guided medical intervention.
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