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

## TL;DR

This study compares two biomarkers, IL-6 and Angiopoietin-2, for predicting severe acute pancreatitis early, finding that Angiopoietin-2 offers more consistent accuracy.

## Contribution

The study provides a systematic comparison of IL-6 and Ang-2 as early severity biomarkers in acute pancreatitis.

## Key findings

- IL-6 shows high but variable accuracy (AUC 0.69–0.99) for predicting severe acute pancreatitis.
- Ang-2 demonstrates consistently high accuracy (AUC 0.79–0.98) across multiple adverse outcomes.
- Combining IL-6 and Ang-2 may improve early prediction of persistent organ failure.

## Abstract

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.