# Progression characteristics of biliary atresia during the waiting period for liver transplantation: a single-center observational study

## TL;DR

The study tracks how biliary atresia rapidly progresses to cirrhosis in children before liver transplantation, identifying key lab markers that predict disease worsening.

## Contribution

The study quantifies the natural progression of biliary atresia cirrhosis and identifies predictive lab markers for clinical deterioration.

## Key findings

- 77.12% of children with biliary atresia progressed to end-stage cirrhosis within about 3 months before liver transplantation.
- Significant changes in lab markers like neutrophil percentage and serum ammonia were linked to disease progression.
- A predictive model using lab markers and initial fibrosis stage accurately forecasted cirrhosis progression in most cases.

## Abstract

Biliary atresia (BA) is a progressive, fibro-obliterative cholangiopathy of infancy that inevitably leads to cirrhosis and liver failure without intervention. While the rapid progression of BA is widely recognized, the precise dynamics of its natural history remain poorly quantified due to the confounding effects of surgical intervention.

This study aimed to characterize the natural progression of BA cirrhosis by analyzing the trajectory of clinical, laboratory, and histological changes during the unique window between diagnostic confirmation by intraoperative cholangiography and subsequent liver transplantation in children who did not undergo Kasai portoenterostomy.

In this single-center, observational study, we analyzed 153 children with cholangiography-confirmed BA who underwent living donor LT without primary Kasai portoenterostomy. The pathological progression of cholestatic cirrhosis and laboratory parameters such as hematological examination and liver function in children with hepatic cholestatic cirrhosis at the two time points were compared to find factors that can predict the progression of BA cirrhosis.

The cohort comprised 153 children with cholangiography-confirmed BA who underwent liver transplantation. The mean age at diagnosing BA was 78.64 ± 31.43 days. The mean interval from exploration to liver transplantation (disease progression time) was 83.36 ± 28.37 days. Within this short period, 77.12% (118/153) of children progressed to end-stage (Stage IV) cirrhosis. Longitudinal analysis revealed a significant increase in white blood cells (WBC, 3.09 ± 5.31 × 109/L), neutrophil percentage (NE%, 7.42 ± 13.77%), total bilirubin (TBIL, 121.9 ± 99.51 μmol/L), and serum ammonia (SA, 6.97 ± 25.59 μmol/L), alongside a significant decrease in hemoglobin (HB, −4.7 ± 15.83 g/L), platelets (PLT, −148.50 ± 154.40 × 109/L), and albumin (ALB, −4.60 ± 7.28 g/L) (all p < 0.05). A predictive model incorporating initial fibrosis stage, waiting time, and changes in NE% and SA demonstrated good accuracy (75.96% in training set, 72.00% in validation set) for forecasting cirrhosis progression.

This study provides unprecedented quantification of the rapid natural progression of BA cirrhosis, revealing a critical 3 month window of clinical deterioration. The dynamic changes in routinely available laboratory markers, particularly neutrophil percentage and ammonia, offer clinically accessible indicators for risk stratification and monitoring, forming a practical “dashboard” for managing BA patients awaiting transplantation in resource-varied settings.