Upregulated beta-defensin-1 in murine and human biliary atresia associates with human native liver survival

TL;DR

High levels of beta-defensin-1 in bile duct disease may predict poor liver outcomes in infants.

Contribution

Identifies hBD1 as a potential biomarker for predicting liver survival in biliary atresia.

Findings

hBD1 is upregulated in both murine and human biliary atresia.

Elevated hBD1 at KPE predicts persistent jaundice and reduced liver survival.

Serum hBD1 levels are higher in BA patients compared to healthy controls.

Abstract

Biliary atresia (BA) is a neonatal cholangiopathy that often progresses to cirrhosis despite timely Kasai portoenterostomy (KPE), and prognostic biomarkers remain undefined. Given its role in adult cholestasis, we evaluated human beta-defensin-1 (hBD1) in murine and human BA for associations with disease progression and outcome. This study analyzed hepatic expression of hBD1 and TGF-ß by qRT-PCR in BA at KPE (n = 36) and liver transplantation (LT, n = 44), and compared with normal (n = 15) and cholestatic disease controls (n = 36). Serum hBD1 was measured by ELISA in BA (n = 23) and healthy infants (n = 11). Murine BD1 was assessed in a Rhesus rotavirus (RRV) BA model. BD1 was found to be upregulated in murine and human BA, with higher expression at LT than at KPE. Hepatic hBD1 correlated with TGF-ß (R2 = 0.21), Ishak fibrosis score (R2 = 0.36), and serum bile acids (R2 = 0.23). Serum hBD1 was elevated in BA versus controls. Elevated hBD1 at KPE predicted persistent jaundice and reduced native liver survival (X2 = 9.5), with ROC analysis showing good discrimination for failure of jaundice clearance at 3 months post-KPE (AUC 0.81 for liver and 0.87 for serum). Thus, hBD1 may serve as a negative predictor of jaundice clearance and native liver survival at the time of KPE.

The online version contains supplementary material available at 10.1038/s41598-026-43602-9.

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