Comparative Evaluation of the Prognostic Accuracy of IL-6 and Angiopoietin-2 for Early Severity Assessment in Acute Pancreatitis: A Systematic Review.

BACKGROUND

Early identification of patients at risk for severe acute pancreatitis (SAP) remains a major clinical challenge. Circulating biomarkers reflecting systemic inflammation (IL-6) and endothelial dysfunction (Ang-2) have emerged as promising tools for improving early prediction of persistent organ failure and other adverse outcomes.

OBJECTIVE

To systematically synthesize and compare the diagnostic and prognostic performance of IL-6 and Ang-2 as early biomarkers of severity in adult patients with acute pancreatitis.

METHODS

This systematic review was conducted in accordance with PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420251177279). PubMed, Scopus, and Web of Science were searched for studies published between 2000 and August 2025. Studies included adult patients (≥18 years) in whom IL-6 and/or Ang-2 levels were measured within 72 h of symptom onset or hospital admission, and where indices of diagnostic accuracy (AUC, sensitivity, specificity, or threshold values) were reported.

RESULTS

Fifteen cohort studies met the inclusion criteria. IL-6 demonstrated a consistent association with SAP and persistent organ failure, with AUC values ranging from 0.69 to 0.99; the highest accuracy was observed within the first 24 h. Specificity varied substantially across studies. Ang-2 showed uniformly high prognostic accuracy (AUC 0.79-0.98), reliably predicting persistent organ failure, multiorgan dysfunction, infected necrosis, and mortality.

CONCLUSIONS

IL-6 exhibits high but heterogeneous diagnostic performance (AUC 0.69-0.99), whereas Ang-2 demonstrates consistently high accuracy (AUC 0.79-0.98) across study designs. Combined evaluation of inflammatory and endothelial pathways appears to offer the most robust strategy for early prediction of persistent organ failure in acute pancreatitis.