Hepatic Fibrogenesis in Paediatric Cholestatic Liver Disease.

Funded Activity Summary

Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is biliary atresia. It develops at, or shortly after birth with progressive destruction of the bile ducts, responsible for transporting bile out of the liver. Without early diagnosis and surgery these infants develop progressive liver scarring leading to liver failure and death or liver transplantation within 1-2 years. It is the commonest reason for liver transplantation in children (55-60%) in the Western world. Even with successful surgery, most, if not all patients will come to liver transplantation over the subsequent 25 years because of ongoing, but slower, scar formation. In older children, diseases like cystic fibrosis cause bile duct blockages leading to progressive liver scarring that is slower and unpredictable, contributing to ill health in up to 20% of patients and death from end stage liver disease or liver transplantation in 5%. Using liver tissue from children with these two disorders we have been able to identify the key cells that control the liver scar process, the Hepatic Stellate Cell. We now need to investigate the role of bile constituents on the scar-forming process in these two diseases. We will utilise a well characterised animal model to investigate the influence of bile constituents on cells isolated from this model and apply these findings back to patient samples to determine their role in paediatric cholestatic liver disease. This will help us to better understand the disease process and importantly, develop more effective and earlier treatment.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $254,250.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Paediatrics

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Bile Acid | Biliary Atresia | Cholangiopathy | Cholestatic Liver Disease | Cirrhosis | Cystic Fibrosis Liver Disease | Hepatic Fibrosis | Hepatic Stellate Cell | Liver Transplantation | Paediatrics

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