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Updated: Jun 13, 2026
A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia
Published on: February 3, 2023
Staging of biliary atresia at diagnosis by molecular profiling of the liver
Katie Moyer1, Vivek Kaimal, Cristina Pacheco
1Division of Pediatric Gastroenterology, Hepatology and Nutrition of Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. katie.moyer@cchmc.org.
Insights
Molecular profiling of liver biopsies in infants with biliary atresia can identify distinct inflammation or fibrosis signatures. This may help stage the disease at diagnosis and predict clinical outcomes, including transplant-free survival.
Area of Science:
- Hepatology
- Molecular Biology
- Pediatric Surgery
Background:
- Biliary atresia (BA) outcome is linked to early portoenterostomy, but disease progression may be influenced by pre-existing biological factors.
- Identifying early disease markers is crucial for managing BA progression.
Purpose of the Study:
- To investigate if molecular profiling of liver tissue at diagnosis can identify distinct stages of biliary atresia.
- To correlate molecular signatures with histological findings, disease severity, surgical response, and survival.
Main Methods:
- Liver biopsies from 47 infants with BA were analyzed for histology (inflammation, fibrosis), gene expression, and association with clinical outcomes.
- Gene expression profiling identified unique molecular signatures in livers with predominant inflammation or fibrosis.
Main Results:
- Fourteen of 47 BA livers showed distinct inflammation (N=9) or fibrosis (N=5) signatures.
- Molecular signatures classified 29/33 additional livers into inflammation or fibrosis groups, validated by histological markers.
- Inflammation signature was associated with younger age; fibrosis signature correlated with decreased transplant-free survival.
Conclusions:
- Molecular profiling at BA diagnosis reveals distinct inflammation or fibrosis signatures in most livers.
- These signatures may represent disease staging at diagnosis and have implications for predicting clinical outcomes.
Background:
Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis.
Methods:
We examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years.
Results:
Fourteen of 47 livers displayed predominant histological features of inflammation (N = 9) or fibrosis (N = 5), with the remainder showing similar levels of both simultaneously. By differential profiling of gene expression, the 14 livers had a unique molecular signature containing 150 gene probes. Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates. The groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, while those with a fibrosis signature had decreased transplant-free survival.
Conclusions:
Molecular profiling at diagnosis of biliary atresia uncovers a signature of inflammation or fibrosis in most livers. This signature may relate to staging of disease at diagnosis and has implications to clinical outcomes.
