The sphincter of Oddi is a valve-like structure, which regulates the flow of bile and pancreatic juice into the gut. The sphincter of Oddi is under complex control involving nerves and hormones. We know that abnormal sphincter of Oddi function (sphincter of Oddi dysfunction) is associated with a number of human diseases including acute pancreatitis. We are able to recognise abnormal sphincter activity, but we do not know what causes it. One possible reason may be that the nerves going to the sph ....The sphincter of Oddi is a valve-like structure, which regulates the flow of bile and pancreatic juice into the gut. The sphincter of Oddi is under complex control involving nerves and hormones. We know that abnormal sphincter of Oddi function (sphincter of Oddi dysfunction) is associated with a number of human diseases including acute pancreatitis. We are able to recognise abnormal sphincter activity, but we do not know what causes it. One possible reason may be that the nerves going to the sphincter along the bile duct (which carries bile from the liver and gallbladder) may be damaged due to the passage of gallstones or during surgery on the bile ducts or gallbladder. We know that the main bile duct is able to sense pressure changes within and communicate this information (via nerves) to the sphincter which inturn alters its activity to relieve the pressure. Where these nerves are located and the chemical messages they use, are unknown. The aim of this project is to gain some of this information. This knowledge may allow us to design different surgical procedures or develop drugs to prevent or manage the abnormal sphincter of Oddi.Read moreRead less
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
Investigation Of The Role Of The Renin-Angiotensin System In Hepatic Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$246,990.00
Summary
Hepatic fibrosis is a common response to chronic liver injury, during which the normal liver architecture is distorted by scar tissue. Hepatic fibrosis can lead to cirrhosis and liver transplantation may be required for patients with liver failure and hepatocellular carcinoma. The chronic liver injury may result from a number of causes including alcohol, persistent viral infections and metabolic disorders. The mechanisms causing fibrosis in liver are similar to those causing fibrosis in other or ....Hepatic fibrosis is a common response to chronic liver injury, during which the normal liver architecture is distorted by scar tissue. Hepatic fibrosis can lead to cirrhosis and liver transplantation may be required for patients with liver failure and hepatocellular carcinoma. The chronic liver injury may result from a number of causes including alcohol, persistent viral infections and metabolic disorders. The mechanisms causing fibrosis in liver are similar to those causing fibrosis in other organs such as kidney and heart. In those organs, the renin-angiotensin system has been shown to contribute to the progression of fibrosis. This system has not been investigated in hepatic fibrosis. We have recently shown in patients with chronic hepatitis C (HCV), that those patients who are genetically pre-disposed to produce higher levels of angiotensin have more liver fibrosis. This application will investigate the role of the renin-angiotensin system in hepatic fibrosis and whether using currently available drugs to inhibit this system can decrease the rate of progression of fibrosis in liver. Liver failure due to chronic HCV infection is currently the leading indication for liver transplantation in Australia. For those patients who fail to respond to anti-viral therapy, there are currently no approved therapeutic options designed to delay or reverse the progression of fibrosis. Based on current known numbers of HCV patients it has been estimated that by the year 2020, over 2000 HCV patients will require a liver transplant each year in Queensland alone. Currently the number of donor livers available allows about 50 transplants per year. Thus there is a desperate need for therapeutic treatments that will delay or reverse the progression of hepatic fibrosis. A successful conclusion to this study will provide a clinically useful treatment strategy that can delay the progression of hepatic fibrosis and thus prevent the need for liver transplantation in many patients.Read moreRead less