Document Type

Article

Publication Date

12-2025

Identifier

DOI: 10.1111/liv.70423; PMCID: PMC12625800

Abstract

BACKGROUND AND AIM: Alagille syndrome (ALGS) is a rare disorder characterised by cholestasis and extrahepatic manifestations. Given the current era of ileal bile acid transporter (IBAT) inhibitor therapies that reduce serum bile acid (SBA) levels, we evaluated whether SBA predicts liver disease outcomes in ALGS.

METHODS: Patients were ascertained from the Global ALagille Alliance (GALA) cohort. A prognostic threshold of SBA 102 μmol/L was assessed as a time-dependent covariate in Cox regression analyses for native liver survival (NLS) and event-free survival (EFS), while adjusting for total bilirubin (TB) levels.

RESULTS: 570 GALA patients were included (348 [61%] male). There was a moderate positive correlation between SBA and TB (Pearson correlation = 0.47, p <  0.001). SBA below 102 μmol/L was a significant predictor of outcomes (NLS: HR = 3.78, 95% CI 2.39-5.99, p <  0.001; EFS: HR = 3.44, 95% CI 2.35-5.04, p <  0.001). SBA remained a significant predictor for improved EFS after adjusting for TB clearance at 1 year (TB <  2 mg/dL; HR = 2.00, 95% CI 1.10-3.65, p = 0.02). Median SBA in the first year of life above 102 μmol/L, predicted lower NLS (67.2% vs. 83.5% at 7 years p = 0.05) and EFS (63.4% vs. 80.9% at 7 years, p = 0.02).

CONCLUSION: Lower SBA in children with ALGS liver disease predicts improved NLS and EFS. SBA is also associated with NLS in children with ALGS who clear their bilirubin, that is, those with anicteric cholestasis. Although the patients studied here did not receive IBAT inhibition, these data suggest that lowering SBA may improve important clinical outcomes.

Journal Title

Liver international : official journal of the International Association for the Study of the Liver

Volume

45

Issue

12

First Page

70423

Last Page

70423

MeSH Keywords

Humans; Alagille Syndrome; Male; Female; Bile Acids and Salts; Child, Preschool; Child; Infant; Prognosis; Bilirubin; Proportional Hazards Models; Cholestasis

PubMed ID

41250932

Keywords

IBAT; cholestasis; paediatrics

Comments

Grants and funding

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Publisher's Link: https://onlinelibrary.wiley.com/doi/10.1111/liv.70423

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