Organ failure-based clinical classification at onset of acute-on-chronic liver failure: a prospective multicenter cohort study

The heterogeneity in ACLF definitions proposed by different expert associations worldwide has led to variations in clinical phenotypes and prognosis. This study proposes a new approach for a unified definition based on the type of organ failure within the first week of disease onset.This prospective cohort study collected clinical data from hospitalized ACLF patients presenting with liver failure (total bilirubin ≥ 5 mg/dL, INR ≥ 1.5) across four liver centers in China. Patients with liver failure within the first week of onset were classified as Type I ACLF, while those with concurrent extrahepatic organ failure were categorized as Type II ACLF. We compared the clinical characteristics and prognosis of Type I and Type II ACLF patients, as well as the inclusivity of these classifications within existing mainstream ACLF definitions.A total of 846 patients were included in the analysis population. Type I ACLF occurred in 86.9% of cases, primarily in patients with non-cirrhotic chronic liver disease (34.3%) or compensated cirrhosis (48.6%), while Type II ACLF, observed in 13.1% of cases, predominantly developed in patients with cirrhosis (73%) (P < 0.001). Mortality rates at 28 and 90 days were significantly higher in Type II ACLF patients (43.2% and 52.3%) compared to those with Type I ACLF (15.8% and 24.9%) (P < 0.001). Patients with Type I ACLF met the APASL criteria more frequently (82.9%), whereas those with Type II ACLF more often met the EASL criteria (69.4%). For predicting the 90-day prognosis in Type I ACLF, the COSSH-ACLF II score achieved the highest AUROC at 0.788 (95% CI: 0.749-0.828). In Type II ACLF, the CLIF-C OF score provided the highest AUROC for predicting 90-day mortality, at 0.902 (95% CI: 0.840-0.964), outperforming the MELD, MELD-Na, and COSSH-ACLF II scores (P < 0.05) and showing no significant difference when compared to the CLIF-C ACLF score (0.872 95% CI: 0.791-0.953, P = 0.426).This new clinical classification approach takes into account the characteristics defined by both Eastern and Western ACLF, and is expected to improve the comparability and interpretability of data in global studies, enhancing global understanding and management of ACLF.