WOFAPS 2025 8th World Congress of Pediatric Surgery

Shilpa Sharma, Hanuman P Sharma, Man Singh

All India Institute of Medical Sciences, New Delhi

PURPOSE: Biliary Atresia (BA) is a dreadful disease with an unpredictable outcome. Various biomarkers have been investigated to predict the prognosis in BA. Recent advances in high-throughput mass spectrometry (MS) have enabled detailed profiling of circulating and excretory biomarkers, offering a non-invasive window into hepatic fibrogenesis. This study synthesizes evidence on the application of MS —particularly liquid chromatography–tandem MS (LC-MS/MS) and data-independent acquisition MS (DIA-MS)—in assessing fibrosis severity and prognosis in BA.

METHOD: A PubMed search done on 18 June 2025, using search words “biliary atresia mass spectroscopy liver fibrosis”, yielded 9 articles. The manuscripts were studied to explore the transformative role of MS in understanding and diagnosing liver fibrosis in biliary atresia and patient care.

RESULTS: LC-MS/MS-based bile acid profiling revealed significantly elevated total and conjugated bile acids in patients with portal hypertension and progressive disease following KPE. Serum levels of fibroblast growth factor 19 (FGF19), quantified alongside bile acids, were reported as a strong predictor of liver fibrosis and transplant-free survival, with FGF19 >109 pg/mL associated with a hazard ratio of 4.31 for poor outcomes. Additionally, reduced levels of 7α-hydroxy-4-cholesten-3-one (C4), a surrogate marker of bile acid synthesis, correlated with advanced fibrosis, suggesting suppressed hepatic bile acid production. Fecal proteomic studies using DIA-MS identified over 100 proteins differentially expressed in BA versus non-BA controls, providing a stool-based diagnostic signature with high discriminatory power (AUC >0.90). Urinary bile acid screening via tandem mass spectrometry has been effective in detecting inborn errors of bile acid synthesis, though overlap with BA necessitates confirmatory testing. Targeted metabolomic approaches further differentiated BA from neonatal hepatitis syndrome using plasma biomarkers such as N-acetyl-D-mannosamine. lncRNA MEG9 was shown to enhance cholangiocyte inflammatory signaling via S100A9 interaction, while ^13C-phenylalanine breath testing correlated well with fibrosis grades. Integration of microbiome sequencing with MS-derived bile acid profiles uncovered dysbiosis in patients with cholangitis post-Kasai portoenterostomy.

CONCLUSION: MS has revolutionized biomarker discovery, enabling multi-platform, high-resolution profiling of bile acids, metabolites, and proteins, facilitating early diagnosis, monitoring, and mechanistic understanding of fibrosis in BA. These tools offer substantial promise for clinical translation and personalized patient care.