Diagnostic Performance of Measurement of Fecal Elastase-1 in Detection of Exocrine Pancreatic Insufficiency: Systematic Review and Meta-analysis

Background & Aims Tests to quantify fecal levels of chymotrypsin like elastase family member 3 (CELA3 or elastase-1) in feces are widely used to identify patients with exocrine pancreatic insufficiency (EPI). However, the diagnostic accuracy of this test, an ELISA, is not clear. We performed a systematic review and meta-analysis to determine the accuracy of measurement of fecal elastase-1 in detection of EPI. Methods We searched PubMed, Embase, and reference lists for articles through November 2016 describing studies that compared fecal level of elastase-1 with results from a reference standard, direct method (secretin stimulation test), or indirect method (measurement of fecal fat) for detection of EPI. Sensitivity and specificity values were pooled statistically using bivariate diagnostic meta–analysis. Results We included total of 428 cases of EPI and 673 individuals without EPI (controls), from 14 studies, in the meta-analysis. The assay for elastase-1, compared to secretin stimulation test, identified patients with pancreatic insufficiency with a pooled sensitivity value of 0.77 (95% CI, 0.58–0.89) and specificity value of 0.88 (95% CI, 0.78–0.93). In an analysis of 345 cases of EPI and 312 controls, from 6 studies, the fecal elastase-1 assay identified patients with EPI with a pooled sensitivity value of 0.96 (95% CI, 0.79–0.99) and specificity value of 0.88 (95% CI, 0.59–0.97), compared to quantitative fecal fat estimation. In patients with low pre–test probability of EPI (5%), the fecal elastase-1 assay would have a false-negative rate of 1.1% and a false-positive rate of 11%, indicating a high yield in ruling out EPI but not in detection of EPI. In contrast, in patients with high pre-test probability of EPI (40%), approximately 10% of patients with EPI would be missed (false negatives). Conclusions In a systematic review and meta-analysis of studies that compared fecal level of elastase-1 for detection of EPI, we found that normal level of elastase-1 (above 200 mcg/g) can rule out EPI in patients with a low probability of this disorder (such as those with irritable bowel syndrome with diarrhea). However, in these patients, an abnormal level of elastase-1 (below 200 mcg/g) has a high false-positive rate.