ACLF Definitions: JCTH | May 2026

• Acute-on-chronic liver failure (ACLF) is a severe syndrome characterized by acute decompensation, organ failure, and high short-term mortality in patients with cirrhosis. However, ACLF lacks a universally accepted definition. Multiple frameworks exist globally, leading to inconsistencies in diagnosis, risk stratification, clinical trials, and regulatory pathways.

• This multinational study compared the newly proposed 2025 consensus ACLF definition with the outcome-based A-TANGO classification, which was designed using mortality-calibrated organ failure thresholds.

• The major challenge in ACLF is balancing harmonization with clinical accuracy. Broader consensus definitions may improve standardization but risk missing clinically important patients if sensitivity declines.

The critical question addressed in this study was:

Does the newer consensus framework accurately identify high-risk ACLF patients, or does it underdiagnose clinically meaningful disease compared with outcome-based models?

• This large multinational study involving nearly 5,000 patients from India and China demonstrated major differences between the two ACLF frameworks.

The A-TANGO model identified substantially more patients as ACLF compared with the consensus definition. Importantly, many patients labeled “non-ACLF” by the consensus criteria but classified as ACLF by A-TANGO had significant short-term mortality, with 28-day mortality ranging from 18%–27%.

A-TANGO consistently showed higher sensitivity for predicting mortality, whereas the consensus definition was more specific but captured a smaller and more advanced liver-centered phenotype.

The study also demonstrated that the consensus “non-ACLF” group was not truly low risk. A-TANGO further stratified these patients into progressively higher mortality groups, revealing hidden clinical heterogeneity.

Overall, the findings suggest that A-TANGO may identify patients earlier in the disease trajectory, potentially at a stage where intervention remains possible. In contrast, the consensus framework appears to diagnose ACLF later, potentially missing high-risk patients with evolving multi-organ dysfunction.

This work has major implications for clinical care, ICU triage, transplant decisions, and future ACLF trial design.