Integrated plasma proteomic and metabolomic profiling demonstrated specific proteins and bile acids remodeling after liver transplantation of children with biliary atresia.

This study aimed to characterize plasma protein and bile acid remodeling after liver transplantation (LT) in children with biliary atresia (BA). Paired plasma samples were collected from seven BA patients before and after LT following unsuccessful Kasai portoenterostomy, and profiled using label-free quantitative proteomics and targeted metabolomics of 15 bile acids. A total of 113 proteins were significantly altered after LT, enriched in pathways governing inflammation, coagulopathy, and extracellular matrix reorganization; eight proteins were selected as signature biomarkers, including upregulated hepatocyte growth factor activator (HGFAC), insulin-like growth factor-binding protein 5 (IGFBP5), insulin-like growth factor-binding protein acid-labile subunit (IGFALS), and coagulation factor XI (F11), together with downregulated phosphatidylinositol-binding clathrin assembly protein (PICALM), S100 calcium-binding protein A11 (S100A11), polymeric immunoglobulin receptor (PIGR), and collagen triple helix repeat-containing protein 1 (CTHRC1). Four conjugated primary bile acids, glycocholic acid (GCA), taurocholic acid (TCA), glycochenodeoxycholic acid (GCDCA), and taurochenodeoxycholic acid (TCDCA), showed precipitous postoperative declines and correlated strongly with clinical liver-injury markers. Two proteins, HGFAC and PIGR, together with these four conjugated bile acids demonstrated high diagnostic accuracy (area under the curve, AUC = 0.86-1.00), supporting their potential as non-invasive biomarkers for monitoring graft function after LT.