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

Shakeev K. Klyuyev D. Ogizbayeva A. Baltabayeva A. Avdienko O. Derevyashkina X.
January 2026 Multidisciplinary Digital Publishing Institute (MDPI)

Diseases
2026 #14 Issue 1

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.

angiopoietin-2 , APACHE II , biomarkers , interleukin-6 , multiorgan dysfunction syndrome , pancreatic necrosis , persistent organ failure , severe acute pancreatitis

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Department of Surgical Diseases, NCJC Karaganda Medical University, Karaganda, 100000, Kazakhstan
Institute of Life Sciences, NCJC Karaganda Medical University, Karaganda, 100000, Kazakhstan
Department of Emergency Medicine, Anesthesiology, and Resuscitation, NJSC Karaganda Medical University, Karaganda, 100000, Kazakhstan
Central Research Laboratory, NCJC Karaganda Medical University, Karaganda, 100000, Kazakhstan
Situation Center, Municipal State Enterprise on the Right of Economic Management Professor Kh. Zh, Makazhanov Multidisciplinary Hospital of the Health Department of the Karaganda Region, Karaganda, 100000, Kazakhstan

Department of Surgical Diseases
Institute of Life Sciences
Department of Emergency Medicine
Central Research Laboratory
Situation Center

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