Diagnostic accuracy of Neutrophil Gelatinase-Associated Lipocalin (NGAL) for inflammatory bowel disease: a systematic review and bivariate diagnostic meta-analysis

To systematically assess the diagnostic accuracy of neutrophil gelatinase-associated lipocalin (NGAL) for inflammatory bowel disease (IBD) and to compare its performance with fecal calprotectin (FC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) using marker-specific diagnostic test accuracy meta-analysis. PubMed, Embase, and the Cochrane Library were searched for diagnostic studies using endoscopy and/or histopathology as the reference standard. The primary synthesis used directly reported complete four-cell table data and marker-specific bivariate random-effects models (Reitsma). Exploratory analyses using sensitivity/specificity records were performed only as supplementary checks because patient populations, thresholds, sample types, and reference standards were not sufficiently exchangeable for a formal diagnostic network meta-analysis. Subgroup feasibility, direct-data sensitivity checks, continuity correction use, and Deeks funnel plot asymmetry were assessed. Seventy-eight studies with 148 diagnostic records were included. The primary bivariate analysis was based on 27 directly reported complete four-cell records, including 11 FC, 7 CRP, 5 ESR, and 4 NGAL records; 85 sensitivity/specificity records were used only for supplementary exploratory analyses. NGAL showed a pooled sensitivity of 90.9% (95% CI: 66.1%-98.1%) and specificity of 76.1% (95% CI: 42.4%-93.2%), but the estimate was imprecise and underpowered because only 13 NGAL records and 4 complete four-cell records were available. Exploratory network diagnostics did not support clinically interpretable ranking. NGAL may have high sensitivity for IBD diagnosis, but current evidence is preliminary, heterogeneous, and based on very limited complete four-cell data. NGAL should not be interpreted as a replacement for FC or as a stand-alone diagnostic test. Larger prospective studies with standardized thresholds, sample types, and reference standards are needed.