Neutrophil Extracellular Trap Scores Predict 90-Day Mortality in Hepatitis B-Related Acute-on-Chronic Liver Failure

Abstract

Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is associated with pronounced systemic inflammation, and neutrophil extracellular traps (NETs) are key components of this response. The primary objective of this study was to establish an NET-related scoring system for patients with HBV-ACLF. A prospective training cohort of 81 patients from the Beijing Ditan Hospital was included. The concentrations of NET markers (cell-free DNA, myeloperoxidase DNA [MPO-DNA], and citrullinated histone H3) in peripheral blood were quantified. Random survival forest, LASSO regression, and multivariate Cox regression analyses were used to identify prognostic factors associated with 90-day mortality in ACLF patients and develop a nomogram for visualization, which was followed by evaluation in a validation cohort (n = 40). NET-related marker levels were significantly higher in the non-survival group than in the survival group (p < 0.05). The NET score was constructed by combining MPO-DNA, neutrophil-to-lymphocyte ratio, and age data. The score’s diagnostic effectiveness, assessed by the area under the curve, yielded values of 0.83 and 0.77 in the training and validation sets, respectively, markedly surpassing those of other established models (p < 0.05). In both groups, the 90-day mortality rates were 88.8% and 75.0%, respectively, for patients categorized as high risk and 18.0% and 12.5%, respectively, for those classified as low risk.