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

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.