Plasma human neutrophil peptides as biomarkers of disease severity and mortality in patients with decompensated cirrhosis

Abstract Background & Aims Human neutrophil peptides (HNP)‐1, ‐2 and ‐3 are the most abundant proteins in neutrophil azurophilic granules and are rapidly released via neutrophil degranulation upon activation. The aims of our study were to assess the role of HNP1‐3 as biomarkers of disease severity in patients with decompensated cirrhosis and their value in predicting short‐term mortality. Methods In this study, 451 patients with acutely decompensated cirrhosis (AD) were enrolled at the two medical centres. Overall, 281 patients were enrolled as the training cohort from October 2015 to April 2019, and 170 patients were enrolled as the validation cohort from June 2020 to February 2021. Plasma HNP1‐3 levels were measured using enzyme‐linked immunosorbent assay (ELISA). Results Plasma HNP1‐3 increased stepwise with disease severity (compensated cirrhosis: 0.3 (0.2–0.4); AD without acute‐on‐chronic liver failure (ACLF): 1.9 (1.3–4.8); ACLF‐1: 2.3 (1.8–6.1); ACLF‐2: 5.6 (2.9–12.3); ACLF‐3: 10.3 (5.7–17.2) ng/ml). From the multivariate Cox regression analysis, HNP1‐3 emerged as independent predictors of mortality at 30 and 90 days. Similar results were observed in the subgroup analysis. On ROC analysis, plasma HNP1‐3 showed better predictive accuracy for 30‐ and 90‐day mortality (area under the receiver operating characteristic (AUROC) of 0.850 and 0.885, respectively) than the neutrophil‐to‐lymphocyte ratio (NLR) and similar accuracy as end‐stage liver disease (MELD: 0.881 and 0.874) and chronic liver failure‐sequential organ failure (CLIF‐SOFA: 0.887 and 0.878). Conclusions Plasma HNP1‐3 levels were closely associated with disease severity and might be used to identify patients with AD at high risk of short‐term mortality.