A Novel Triple-Biomarker Score Predicts Mortality in Acute Pancreatitis

Predicting severe outcomes in acute pancreatitis (AP) remains a challenge. The interplay between endothelial dysfunction and systemic inflammation is pivotal in disease progression, but the combined prognostic value of their biomarkers is not well defined. The aims of this study were: 1) to define the interactions between endothelial dysfunction biomarkers and cytokines in patients with AP; 2) to evaluate the prognostic value of triple-marker model regarding prediction of survival in AP.

In a prospective cohort of 100 AP patients, we serially measured biomarkers of endothelial dysfunction (vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), endothelin, E-selectin) and inflammation (tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), procalcitonin) on admission (day 0), day 1, and day 7. We employed correlation analyses, logistic regression, and receiver operating characteristic (ROC) analysis to assess their individual and combined ability to predict mortality.

A strong correlational network was observed, particularly among TNF-α, endothelin, E-selectin, CRP, and procalcitonin (all r > 0.75, P < 0.01). While VEGF correlated with TNF-α (P < 0.001), vWF did not show a significant bilateral correlation with it. Crucially, logistic regression revealed that the three-way interaction between vWF, TNF-α, and CRP was a significant predictor of mortality (P = 0.050). This triple-marker model demonstrated excellent predictive power for survival, with an area under the curve (AUC) of 0.861 in ROC analysis (P < 0.001). Kaplan-Meier analysis confirmed that patients with a high vWF-TNF-α-CRP interaction score had significantly lower survival rates (69.2% vs. 98.4%, P < 0.001).

The combination of endothelial and inflammatory markers is a more powerful prognostic tool than any marker in isolation. The vWF-TNF-α-CRP interaction model effectively identifies AP patients at high risk of mortality, potentially enabling earlier targeted interventions. This underscores the critical role of the endothelial-inflammatory axis in determining AP outcomes.