Liver Failure versus Organ Failure in Acute-on-Chronic Liver Failure: Sequence and Consequence

Background/Aims: Acute-on-chronic liver failure (ACLF) is characterized by the acute decompensation of the liver in patients with preexisting chronic liver disease or cirrhosis, often resulting in multiorgan failure and high short-term mortality. This study aimed to investigate the sequence of organ failures, particularly liver and renal failure, and their impact on the short-term survival in ACLF patients. Methods: We analyzed data from 1,765 patients in a prospective Korean ACLF cohort, focusing on the timing of liver and renal failures. Overall survival (OS) was assessed using Kaplan-Meier survival analysis with the log-rank test, and multivariate analysis was performed using a Cox proportional hazards model. Results: Patients with initial liver failure had significantly worse OS compared to those without liver failure (adjusted hazard ratio [aHR], 3.6; p=0.008), and those who developed liver failure during the disease course had an even poorer prognosis (aHR, 5.7; p=0.002). There was no significant difference in OS between patients without renal failure and those with initial renal failure (aHR, 0.8; p=0.508). However, renal failure that developed during hospitalization was associated with a worse prognosis (aHR, 1.9; p=0.056). Patients with initial renal failure had significantly better OS than those with initial liver failure (aHR 2.4, p=0.040). Conclusions: Organ failure developing during hospitalization is more detrimental than failure present at admission. ACLF with initial renal failure has a better prognosis than ACLF with initial liver failure. ACLF patients with initial renal failure have a 28-day survival rate exceeding 90% if renal failure is present initially; however, this rate significantly decreases if renal failure occurs during hospitalization.