Early prediction of acute-on-chronic liver failure development in patients with diverse chronic liver diseases

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days. Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 10⁹/L; 1 or 0] × 0.49 + [PLT < 100, 10⁹/L; 1 or 0] × 0.44 + [TBIL ≥ 35, µmol/L; 1 or 0] × 0.05 + [HDL-C < 0.5, mmol/L; 1 or 0] × 1.04 - Ln[Hb, g/L] × 0.89 + [BUN > 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P < 0.001). Additionally, the new score improved in predictive accuracy, time-dependent receiver operating characteristics, probability density function evaluations, and calibration curves, making it highly predictive for the onset of ACLF at all time points. The optimal cut-off value of 9.6 effectively distinguished between high- and low-risk patients for ACLF onset. These findings were further validated in a separate cohort of patients. A new progressive score, based on seven predictors, has been developed to accurately forecast the occurrence of ACLF within 7, 14, and 28 days in patients with various chronic liver diseases. This tool may be utilized to identify high-risk patients, tailor follow-up management, and guide the escalation of care, prognostication, and transplant evaluation.