Molecular and cellular pathogenesis of nonalcoholic steatohepatitis: Insights from human studies [ 2003 - 2004 ]

Research Grant

Researchers: Prof Jacob George (Principal investigator) ,  Isabelle Leclercq ,  Prof Geoffrey Farrell

Brief description Nonalcoholic steatohepatitis (NASH) is the commonest cause for liver disease in Australia. On liver biopsy it is characterised by changes similar to that induced by alcohol, but occurs in individuals who consume minimal amounts of alcohol. The risk factors for the development of NASH include obesity, type II diabetes and hyperlipidemia. As the prevalence of obesity and diabetes are rapidly increasing in Australia, it is evident that NASH will become of major public health concern in the future. In those that develop liver disease from NASH, a proportion (10-30%) will develop advanced liver scarring leading to significant morbidity and mortality. The overall aim of this proposal is therefore to provide insight into why some people with fatty liver disorders develop NASH and to determine the basis for disease progression in this condition. Over the last decade, work at the Storr Liver Unit in a nutritional animal model of NASH has suggested potential mechanisms for disease progression in NASH. This proposal seeks to determine whether such mechanisms operate in human NASH by conducting studies in a large cohort of well chracterised patients with this disorder. Advances in molecular and cellular biology now permit such studies by anaylsis of small quantities of tissue such as that obtained at the time of liver biopsy. In this proposal we will examine both serum and liver tissue to characterise the role of oxidative stress (the biologic equivalent of rusting), the host immune response, liver cell injury and damage to the metabolic machinery within cells as determinants of diease severity in NASH. It is anticipated that these studies will provide the most comprehensive data to date on the pathogenesis of NASH and should suggest potential therapeutic targets for treating this condition.

Funding Amount $AUD 215,500.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant