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Updated: Jun 8, 2026

A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia
Published on: February 3, 2023
Serum and tissue transforming [corrected] growth factor β1 in children with biliary atresia
Fernanda dos Santos de Oliveira1, Carlos Oscar Kieling, Jorge Luiz dos Santos
1Universidade Federal do Rio Grande do Sul, CEP-90035-903, Brazil.
Insights
Transforming growth factor β1 (TGFβ1) levels are high during active biliary atresia (BA) fibrosis but decrease after liver transplantation. This suggests TGFβ1 may indicate fibrotic activity in BA patients.
Area of Science:
- Hepatology
- Pediatric Gastroenterology
- Biomarker Discovery
Background:
- Biliary atresia (BA) is a severe infantile liver disease causing bile duct obstruction and liver failure.
- Current diagnosis and fibrosis staging rely on invasive liver biopsy.
- There is a need for noninvasive biomarkers to assess fibrosis in BA.
Purpose of the Study:
- To evaluate serum and tissue transforming growth factor β1 (TGFβ1) and the AST-to-platelet ratio index (APRI) as potential noninvasive biomarkers for biliary atresia (BA).
- To correlate these markers with liver tissue collagen density to assess fibrotic progression.
- To determine if TGFβ1 and APRI can differentiate disease states in BA patients.
Main Methods:
- Serum and tissue samples from BA patients at diagnosis and liver transplantation were analyzed.
- Transforming growth factor β1 (TGFβ1) levels were measured.
- The AST-to-platelet ratio index (APRI) was calculated.
- Tissue collagen density was quantified and correlated with biomarker levels.
Main Results:
- Serum TGFβ1 levels were highly variable at diagnosis but significantly decreased at liver transplantation compared to controls.
- No significant correlation was found between serum TGFβ1 and collagen density.
- Serum TGFβ1 showed no correlation with APRI at diagnosis but an inverse correlation with platelet count.
- All patients at transplantation had low serum TGFβ1 and APRI values greater than 2.0.
Conclusions:
- TGFβ1 expression is higher during active fibrogenesis in BA and reduced in later stages with scar tissue.
- Low TGFβ1 at liver transplantation may have implications for immune response and cell growth post-transplant.
- Further validation in larger cohorts is needed to confirm TGFβ1's role as a biomarker in BA.
Background:
Biliary atresia (BA) is an infantile disorder characterized by the obstruction of a portion or the entirety of the extrahepatic bile ducts, leading to hepatic fibrosis and loss of liver function. The gold standard for diagnosing and grading fibrosis is liver biopsy, but there are many groups searching for noninvasive biomarkers that could replace and/or complement this procedure.
Methods And Materials:
In this study, we evaluated serum and tissue transforming growth factor β1 (TGFβ1) and aspartate aminotransferase [AST]-to-platelet ratio index (APRI) in patients with BA at the time of diagnosis and at liver transplantation and correlated these data with tissue collagen density, to verify if they could act as biomarkers for BA.
Results:
At the time of diagnosis, TGFβ1 levels were highly variable in BA patients. However, serum values at transplantation were significantly decreased (13.75 ± 3.68 ng/mL) as compared to controls (34.36 ± 9.35 ng/mL) (P = .01). No correlation was found between serum TGF1β1 and collagen density in both groups analyzed. Serum TGFβ1 showed no correlation with APRI at diagnosis. At the time of liver transplantation, all patients had low serum TGFβ1 and variable APRI, although all higher than 2.0. However, when platelet count was used, an inverse correlation with serum TGFβ1 was observed at the time of diagnostics (r(2) = 0.749; P = .03).
Conclusions:
Our findings suggest that at the time of diagnosis the fibrogenic process is active, with higher levels of TGFβ1, whereas later on, there is scar tissue, with reduced TGFβ1 expression. Although our results should be confirmed in larger sets of patients with BA, the lack of TGFβ1 at the time of liver transplantation may have important consequences for the patient because it is a pleiotropic molecule, responsible for many functions in the body, mainly those related to immune response and cell growth.
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