# 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.

## Key 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.