Targeting The Pathophysiology And Therapy Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$484,006.00
Summary
Hepatic fibrosis, or scarring of the liver, is a serious condition which can lead to liver cancer or death. Treatment of liver scarring is currently not effective once the scarring is well developed. This project aims to examine agents which may act to halt liver scarring once it has already developed. Outcomes from this project may help provide potential treatments to reduce the need for liver transplantation or to reduce patient deaths.
Identification Of The Mechanisms Of Hepatic Fibrogenesis Aid In The Detection And Prediction Of Clinical Outcomes In Paediatric Cholestatic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Biliary Atresia (BA) and Cystic Fibrosis Liver Disease (CFLD) are important causes of childhood cirrhosis. Diagnosis is difficult, treatments problematic, and outcomes suboptimal. In BA, bile duct obstruction in infants rapidly progresses to liver failure. It is the most common indication for liver transplantation in children. CFLD causes significant morbidity/mortality in about 20% of CF children. This proposal investigates the mechanisms of liver fibrosis (scarring) and the role of fibrosis in ....Biliary Atresia (BA) and Cystic Fibrosis Liver Disease (CFLD) are important causes of childhood cirrhosis. Diagnosis is difficult, treatments problematic, and outcomes suboptimal. In BA, bile duct obstruction in infants rapidly progresses to liver failure. It is the most common indication for liver transplantation in children. CFLD causes significant morbidity/mortality in about 20% of CF children. This proposal investigates the mechanisms of liver fibrosis (scarring) and the role of fibrosis in both diagnosis and predicting clinical outcome.Read moreRead less
HLA-G/H2-Bl Is Critical For Regulating Inflammation In The Liver
Funder
National Health and Medical Research Council
Funding Amount
$494,050.00
Summary
The key factor to induction of liver fibrosis, progression to cirrhosis, and hepatocellular carcinoma is inflammation. Liver transplant and liver regeneration following liver resection are also dramatically impaired by elevation of inflammation. We have identified a potent anti-inflammatory protein, HLA-G, that is critical for regulating post-surgical inflammation in the liver. We will determine if HLA-G can reverse and/or block liver fibrosis and modify HLA-G for improved clinical potential.
Application Of Follistatin To The Resolution Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$330,990.00
Summary
Liver fibrosis or scarring is a consequence of a number of diseases, leading eventually to extensive damage known as cirrhosis. It is a significant health problem both here in Australia and overseas with around 180,000 patients diagnosed each year in the Western world. Cirrhosis arises from many causes, two major groups being patients who contract hepatitis and alcoholics. People with cirrhosis have a much increased risk of liver failure, which requires liver transplantation, or of developing li ....Liver fibrosis or scarring is a consequence of a number of diseases, leading eventually to extensive damage known as cirrhosis. It is a significant health problem both here in Australia and overseas with around 180,000 patients diagnosed each year in the Western world. Cirrhosis arises from many causes, two major groups being patients who contract hepatitis and alcoholics. People with cirrhosis have a much increased risk of liver failure, which requires liver transplantation, or of developing liver cancer, for which current treatments have limited success. We have been studying two proteins, activin and follistatin, both of which are made in the liver. We are interested in activin because it is one of the body's mechanisms to control cell growth, and also seems to stimulate the development of scar tissue. Follistatin is the natural inhibitory substance for activin. It blocks the effects of activin and helps promote cell growth in the liver. We believe that follistatin may also be useful in controlling liver scarring. This process will be studied in animal models of cirrhosis, in the hope that follistatin treatment will reduce the level of liver damage. If successful, this would be important information that would enable us to design treatments applicable to human sufferers of these liver diseases. In another part of the project, we will assess whether activin and follistatin might be useful markers of liver disease. Most patients require a liver biopsy to assess the amount of liver damage, and a simple blood test would be a far easier, less traumatic and cheaper alternative.Read moreRead less
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.
A Pilot Study To Evaluate The Safety Of Intravenously Administered Human Amnion Epithelial Cells In Patients With Compensated Cirrhosis
Funder
National Health and Medical Research Council
Funding Amount
$394,692.00
Summary
We propose a first-in-man clinical trial of human amnion epithelial cells (hAEC), a stem cell from the placenta, to assess safety in patients with stable liver cirrhosis. Worldwide, cirrhosis is the 6th most common cause of death. Liver transplantation remains the only chance for survival for some people with cirrhosis. In animal models, hAEC can substantially reduce liver scar tissue. Our goal is to develop hAEC as a therapy to reduce the need for liver transplantation.
The Role Of The Adiponectin Receptors In Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$393,159.00
Summary
Advanced liver scarring (fibrosis) contributes to the death of 1500 Australians annually. Two-thirds of our community is overweight or obese, and this worsens liver disease. A protein secreted by fat, adiponectin, may be important as it acts on liver cells to promote fibrosis. To understand adiponectins role, we will use mice null for adiponectin receptor genes and study its action on liver cells. This study will improve our understanding of liver scarring biology and patient treatments.
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.