Abstract
BACKGROUND: Acute-on-chronic liver failure (ACLF) is characterized by severe metabolic disturbances; however, the specific metabolomic features and their predictive value on 90-day prognosis remain unclear. AIM: To identify serum metabolomic changes in patients with ACLF with different prognoses to support clinical prediction of outcomes and treatment decisions. METHODS: This non-interventional, observational case-control study enrolled 58 patients with ACLF. Fasting venous blood samples were analyzed using targeted metabolomics. Univariate and multivariate statistical analyses identified differential metabolites among 18 amino acids, 11 fatty acids, 5 gut microbiota-related metabolites, and 4 bile acid metabolites. Binary logistic regression identified independent mortality risk factors, visualized via forest plots and receiver operating characteristic curves. RESULTS: Significant differences (P < 0.05) were observed between the death and survival groups in baseline age, model for end-stage liver disease score, model for end-stage liver disease with sodium, neutrophil-to-lymphocyte ratio (NLR), total bilirubin, serum creatinine, blood urea nitrogen, and platelet count. Metabolites, including L-carnitine, creatinine, alanine, arginine (Arg), proline, choline, and oleic acid, also showed statistically significant differences between the groups. Multivariate analysis identified age, NLR, and Arg as independent risk factors for 90-day mortality in patients with ACLF. The predictive model, age-NLR-Arg = -15.481 + 0.135 × age + 0.156 × NLR + 0.203 × Arg, with a cutoff of 0.759, achieved an area under the receiver operating characteristic curve of 0.945 with sensitivity of 84.0% and specificity of 87.9%. CONCLUSION: The age-NLR-Arg model demonstrates a strong predictive value for 90-day mortality risk in patients with ACLF.