41 A multi-marker panel predicts the likelihood of biliary atresia in infants with superior specificity than current practice

Background Timely diagnosis of biliary atresia (BA) is crucial since better outcomes are associated with early surgical intervention, namely, the Kasai procedure. However, current diagnostic practice using biomarker, imaging and biopsy pathology lacks specificity therefore BA diagnosis needs to be made during the invasive operation. Several biomarkers are used to predict the likelihood of BA in conjunction with ultrasound and liver biopsy, including hepatic panel of total bilirubin (TBil), direct bilirubin (DBil), gamma-glutamyl transferase (GGT), clotting factors, as well as a novel biomarker, matrix metalloproteinase 7 (MMP-7). In a recent retrospective analysis of BA and non-BA cholestatic infants, serum MMP-7 demonstrated higher discriminative performance than other clinical markers including GGT, stool color and pathology. Objective The study examines the clinical performance of a multi-marker panel that combines MMP-7, GGT, Tbil and DBil compared to conventional hepatic panel (GGT, Tbil and DBil ) or MMP-7 alone for discriminating BA from non-BA cholestasis. Methods Infants in a single pediatric center with serum MMP-7 results as part of the cholestasis workup from July 2023 to January 2025 were included. Plasma Tbil, DBil and GGT results measured on Atelica (Siemens) or Alinity (Abbott) with collection date closest to that of MMP-7 (<15 days) were retrieved. MMP-7 was measured by an in-house time-resolved fluorescence energy transfer immunoassay. BA diagnosis was confirmed by Kasai procedure. This study received approval from the Institute Review Board. Results A total of 88 patient encounters were included in the study. The median age at MMP-7 collection was 42 days (interquartile range 21-63 days) with 62 males and 26 females. Ten patients were diagnosed with BA during the Kasai procedure. Three criteria were evaluated against clinical diagnosis for their performance. 1. Hepatic panel: Tbil, Dbil, and GGT all above age-specific reference interval (RI). 2. MMP-7 above 18.2 ng/mL as proposed in Pandurangi S et al 2024. 3. A multi-marker panel: MMP-7 above 18.2 ng/mL, Dbil/Tbil ratio above 50%, and GGT above 1.5 times of age-specific RI upper limit. All 3 criteria demonstrated high sensitivity (criterion 1: 90%, 2: 100%, 3: 90%), while the specificity was 42%, 67% and 86%, respectively. Specificity of this novel multi-marker panel was the highest to our knowledge among non-invasive diagnostics approaches reported in the literature so far. Conclusion A multi- biomarker panel composed of Tbil, Dbil, GGT, MMP-7 with age-specific RI predicts the likelihood of BA in infants with much improved specificity than conventional hepatic markers or MMP-7 alone. Our study is the first to evaluate the diagnostic performance of MMP-7 combined with conventional blood markers in a real-life scenario with a representative BA prevalence in cholestatic infants. It shows promise to guide management of patients at risk for BA for favorable outcomes.