One Size Does Not Fit All: Personalised Exercise Strategies To Improve Cardiovascular And Metabolic Health In Patients With Non-alcoholic Fatty Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Non-alcoholic fatty liver disease (NAFLD) affects one third of Australian adults and is linked with numerous chronic health conditions. Regular exercise reduces NAFLD, even without weight loss. However, response to exercise therapy is highly variable and there is a need for more personalised approaches. This research will identify which personalised exercise strategies effectively treat NAFLD, and, which measures can accurately monitor the progression of the disease in clinical practice.
Novel Therapies Targeting The Alternate Renin Angiotensin System In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,284,565.00
Summary
Scarring of the liver due to chronic liver diseases (cirrhosis) is now a major cause of illness and death in Australia. This project will study whether drugs and gene therapy approaches targeting a hormone system called the renin angiotensin system can be used to prevent the development of cirrhosis and its complications.
The Role Of Steatosis In Promoting Cellular Injury And Fibrogenesis In Human Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$414,375.00
Summary
Lay Description Fatty liver (steatosis) is important because it increases the vulnerability of the liver to factors that trigger inflammation and fibrosis. Patients with steatosis may develop steatohepatitis spontaneously and this increases the risk and rate of progression to cirrhosis, with consequent liver-related morbidity and mortality. In addition, steatosis significantly potentiates the severity of liver damage that is caused by other agents such as drugs or infections. To improve the prog ....Lay Description Fatty liver (steatosis) is important because it increases the vulnerability of the liver to factors that trigger inflammation and fibrosis. Patients with steatosis may develop steatohepatitis spontaneously and this increases the risk and rate of progression to cirrhosis, with consequent liver-related morbidity and mortality. In addition, steatosis significantly potentiates the severity of liver damage that is caused by other agents such as drugs or infections. To improve the prognosis of patients with fatty livers, it is important to understand why hepatic steatosis increases the risk for more serious liver disease. To date, much of our understanding of mechanisms of liver injury in fatty liver disease comes from animal models, and these findings have not been systematically evaluated in the human disease. Apart from optimizing body weight, there is no established treatment of fatty liver disease. Delineation of the mechanisms involved in liver injury will allow the development of specific protective strategies for steatotic livers.Read moreRead less
The AGE/RAGE Pathway In Chronic Liver Disease; A Novel Target For Prevention And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$461,822.00
Summary
Cirrhosis of the liver due to non-alcoholic fatty liver disease, chronic hepatitis and other liver diseases is now a major cause of illness and death in Australia. This project will examine how advanced glycation end products (AGEs), compounds formed in the body and also derived from our diet, contributes to the progression of liver scarring in these diseases. We will study whether drugs targeting these compounds can be used to reduce liver scarring and prevent the development of cirrhosis.
The Alternate Renin Angiotensin System; A Novel Target For The Prevention And Treatment Of Liver Fibrosis And Portal Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$693,950.00
Summary
Cirrhosis of the liver due to chronic hepatitis and other common liver diseases is now a major cause of illness and death in Australia. This project will examine how a hormone system called the renin angiotensin system contributes to the development of liver damage in these diseases. We will study whether drugs targeting this system can be used to reduce liver scarring and prevent the development of cirrhosis and its complications.
Monocytes/macrophages In Chronic Liver Diseases: Cross-talk With Hepatocytes And Nonparenchymal Cells And Role In Progressive Liver Injury
Funder
National Health and Medical Research Council
Funding Amount
$598,645.00
Summary
More than 170 million people world-wide are chronically infected with the hepatitis C virus. Approximately 10-15% of chronically infected subjects develop cirrhosis with its attendant risks of liver failure and hepatocellular carcinoma. The objective of this important project is to examine the mechanisms by which monocytes and macrophages (cells of the immune system) enhance or impair the progression of liver disease and response to antiviral treatment in patients with chronic hepatitis C.
Molecular And Cellular Pathogenesis Of Nonalcoholic Steatohepatitis: Insights From Human Studies
Funder
National Health and Medical Research Council
Funding Amount
$215,500.00
Summary
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. ....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.Read moreRead less