Early Biomarkers for Severity in Acute Pancreatitis; a Systematic Review and Meta-analysis

Background: Acute pancreatitis is complicated by local and/or systemic complications in 30% of the patients. The prediction of severity with current clinical scores and biomarkers, such as the Acute Physiology And Chronic Health Evaluation (APACHE) II score and C-reactive protein (CRP), are hampered by limited negative predictive values. Methods: We performed a systematic review and meta-analysis. MEDLINE, EMBASE, Web of Science and Cochrane library were searched for studies. Eligible were cohort or case-control studies that reported accuracy data of laboratory biomarkers for the prediction of severity, defined by the Atlanta 1992 criteria. Screening, data-extraction and risk of bias assessment (QUADAS-2) were done in duplicate. Pooled analysis was done when three or more studies reported accuracy data for the same laboratory biomarkers within 24 hours of admission. APACHE-II score was included for comparison. Meta-analysis was performed using the HSROC model for different cut-off values, and bivariate random effects models for comparable cut-off values. Meta-regression was done to compare summary sensitivity and specificity among the biomarkers. Results: We included 147 studies in the qualitative analysis, reporting on 23 biomarkers. HSROC analysis using different cut-off values showed that interleukin-6 (IL-6) and polymorphonuclear leukocyte elastase (PMN-E) were superior in predicting severity within 24 hours of admission compared with CRP and APACHE-II. Bivariate analysis of markers with comparable cut-offs resulted in summary sensitivities and specificities of 93% and 90% for IL-6 (>50 pg/ml), 72% and 72% for APACHE-II (>7), and 60% and 85% for CRP (>150 mg/l), respectively (Figure). In meta-regression, IL-6 showed higher sensitivity and specificity compared with CRP (p=0.001 and p=0.227, respectively) or APACHE-II (p=0.13 and p=0.043, respectively). Conclusion: This study indicates that IL-6 with a cut-off value of 50 pg/ml is superior in the early prediction of severe acute pancreatitis compared to widely used prediction methods that are recommended by the guidelines.