Biliary atresia-related liver fibrosis

Biliary atresia (BA) is a devastating cholestatic disease of infancy characterized by progressive fibro-obliterative cholangiopathy, which, without timely intervention, inexorably leads to end-stage liver disease and the need for liver transplantation. Hepatic fibrosis constitutes not only the histopathological cornerstone of BA but also the principal determinant of disease trajectory, native liver survival, and long-term outcomes. This review provides a comprehensive synthesis of the current understanding and unmet clinical needs in BA-associated liver fibrosis, systematically addressing three interconnected domains: pathogenesis, diagnostic modalities, and therapeutic strategies. In the pathogenic realm, the authors dissect the multilayered molecular architecture-from genetic susceptibility loci through aberrant cellular activation to the integrated signaling network of TGF-β/Smad, Wnt/β-catenin, Hippo/YAP, and Notch pathways, further sustained by epigenetic modifications involving DNA methylation, histone remodeling, and non-coding RNAs. In diagnostics, conventional ultrasound, emerging shear wave elastography, serum matrix metalloproteinase-7 as a promising biomarker, and risk-stratification algorithms are evaluated, while their strengths and limitations are critically compared. In therapeutics, the enduring role of Kasai portoenterostomy is assessed, alongside the limitations of current adjunctive therapies and the evolving landscape of pharmacological interventions-including ileal bile acid transporter inhibitors, farnesoid X receptor agonists, eicosapentaenoic acid, and N-acetylcysteine-alongside ongoing clinical trials. Single-cell and spatial transcriptomic technologies are highlighted as revolutionizing our comprehension of cellular heterogeneity and intercellular crosstalk within the fibrotic niche, offering unprecedented opportunities for molecular subtyping and precision medicine. By bridging mechanistic insights with clinical translation, this review provides a conceptual framework to guide future research, improve diagnostic precision, and develop rationally targeted combination therapies for BA-associated liver fibrosis.