ACLF-Again: A Novel Clinical Entity With Poorer Outcomes Following Reversal of Acute-on-Chronic Liver Failure-A...

Acute-on-chronic liver failure-Again (ACLF-Again) is an entirely new and undiscovered entity in patients with chronic liver disease, can be defined as re-emergence of ACLF following reversal from an initial ACLF episode. This study aimed to evaluate the interval between ACLF episodes, duration of reversal, severity, precipitating factors, and assess outcome and predictors of ACLF-Again.

This study was conducted from June 2023 to December 2024 and included patients admitted with ACLF as defined by the Asian Pacific Association for the Study of Liver (APASL). They were studied for their severity and outcome. All survivors were then followed up every two weeks for 12 months. Those who achieved reversal of ACLF and redeveloped ACLF on follow-up were included as ACLF-Again. Data on first episode of ACLF and ACLF-Again were compared.

Out of 212 ACLF patients, 171 were discharged (41 died) and followed up, out of which 26 developed ACLF-Again. ACLF-Again was significantly associated with higher baseline APASL, ACLF Research Consortium (AARC)-ACLF scores (P < 0.014), international normalized ratio (P < 0.033), and creatinine levels (P < 0.005) compared to first episode of ACLF. Key precipitating factors during ACLF-Again included continued alcohol consumption (46.15%), infections (42.30%), acute portal vein thrombosis (3.84%), and unknown causes (7.69%). ACLF-Again patients had a longer mean hospital stay (12 days versus 9.23 days) and higher mortality (30.8% versus 19.33%) compared to the first episode of ACLF. Median interval between two ACLF episodes was 92 days (range: 50-270 days, interquartile range: 63.5-120 days). ACLF-Again had higher AARC-ACLF scores (mean: 11.5 versus 9.57) and more organ failures.

ACLF-Again is a distinct clinical entity and it exhibits poor prognosis with higher AARC-ACLF scores and more organ failures. Effective management requires addressing precipitants, particularly alcohol abuse and infections along with optimizing chronic liver disease care.