Abstract / Summary
Biliary atresia (BA) is a progressive neonatal hepatobiliary disease where early diagnosis is critical for the success of Kasai portoenterostomy. However, differentiating BA from other causes of neonatal cholestasis remains a significant clinical challenge. While matrix metalloproteinase-7 (MMP-7) has emerged as a promising biomarker, its clinical translation is hindered by the lack of technical standardization and the slow turnaround time of manual ELISA platforms. We aimed to develop and validate a proprietary, fully automated chemiluminescence immunoassay (CLIA) platform for rapid and precise serum MMP-7 quantification. Serum MMP-7 diagnostic efficacy was evaluated using a three-stage validation framework comprising retrospective discovery ( n = 148), medical reference interval establishment ( n = 175), and prospective multicenter validation ( n = 172). MMP-7 robustness across various neonatal conditions, comparison with conventional liver markers, and real-world performance of the automated assay at a pre-defined diagnostic cutoff were examined. In the retrospective phase, serum MMP-7 demonstrated superior discriminative power compared to traditional biochemical markers (AUC = 0.968, 95% CI: 0.943–0.992). The established medical reference interval for healthy neonates was 5.90–18.49 ng/mL, leading to a designated diagnostic cutoff of 18.5 ng/mL. In the prospective multicenter cohort, the automated platform achieved exceptional diagnostic efficacy with an AUC of 0.988 (95% CI: 0.972-1.000). At the 18.5 ng/mL threshold, the assay yielded a sensitivity of 100% (95% CI: 89.5%-100%), a specificity of 98.6% (95% CI: 94.9%-99.6%), and a negative predictive value of 100% (95% CI: 97.3%-100%). Diagnostic efficacy remained highly consistent between the retrospective discovery and prospective validation cohorts ( p = 0.1605). The fully automated serum MMP-7 CLIA platform provides a rapid, standardized, and highly precise solution for the early differential diagnosis of BA. By facilitating timely surgical intervention and accurately identifying non-BA infants, this platform warrants evaluation in future implementation trials to test the hypothesis of whether its use as a diagnostic triage aid can safely reduce unnecessary invasive procedures and optimize referral timing. Guangdong Medical Products Administration, No. 20,250,141. Registered 14 April 2025, https://www.gdzwfw.gov.cn/ .