Non‐invasive biomarkers in biliary atresia: A scoping review of fibrosis assessment, translational readiness and clinical implementation gaps

Abstract

Abstract Background Biliary atresia (BA) is a progressive fibro‐inflammatory cholangiopathy in which liver fibrosis influences clinical outcomes. Although liver biopsy remains the reference standard for fibrosis assessment, it is invasive and unsuitable for longitudinal monitoring. Numerous non‐invasive biomarkers have been proposed, but their readiness for clinical implementation remains uncertain. This review synthesised evidence on biomarkers associated with histological fibrosis severity in BA and evaluated their translational readiness and clinical utility. Methods A scoping review was conducted in accordance with the Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR) guidelines. MEDLINE and Scopus were searched for human studies published between January 2019 and July 2025. Eligible studies evaluated associations between non‐invasive biomarkers and histological liver fibrosis at diagnosis or Kasai portoenterostomy (KPE). Biomarkers were classified by pathobiological mechanism, U.S. Food and Drug Administration (FDA)‐National Institutes of Health (NIH) Biomarkers, EndpointS and other Tools (BEST) category and translational readiness level (TRL). Results Thirty‐eight studies met the inclusion criteria. Most (33/38; 86.8%) reported significant associations with fibrosis severity. Biomarkers were categorised by mechanism (e.g., fibrogenesis, imaging and inflammatory). Serum matrix metalloproteinase‐7 (MMP‐7) and elastography demonstrated the highest translational maturity, being the only tools supported beyond early validation. Conversely, most molecular, metabolic and inflammatory candidates remain at proof‐of‐concept or analytical validation stages. Substantial methodological heterogeneity remains regarding thresholds and reference standards. Conclusions The challenge in BA biomarker research has shifted from discovery to clinical implementation. While MMP‐7 and elastography are the most mature tools, none of them currently serves as a standalone determinant of management. Future progress requires methodological standardisation, multicentre validation and the integration of biomarkers into multimodal clinical decision‐making frameworks to meaningfully improve patient care.