DEVELOPMENT OF CLINICALLY APPLICABLE STRATEGIES TO INDUCE AND MONITOR LONG TERM ACCEPTANCE OF LIVER ALLOGRAFTS
Funder
National Health and Medical Research Council
Funding Amount
$287,036.00
Summary
Liver transplantation is the only therapy for end-stage liver disease and thousands of Australian lives have been saved with this treatment. The major complication of liver transplantation is rejection which leads to loss of about half of the transplanted livers by ten years. Liver transplants in many animal models are not rejected and function normally for the life of the animal. Using one such animal model we have shown that white cells from the donor are responsible for the absence of rejecti ....Liver transplantation is the only therapy for end-stage liver disease and thousands of Australian lives have been saved with this treatment. The major complication of liver transplantation is rejection which leads to loss of about half of the transplanted livers by ten years. Liver transplants in many animal models are not rejected and function normally for the life of the animal. Using one such animal model we have shown that white cells from the donor are responsible for the absence of rejection. Of interest, these cells appear to stimulate a rapid and extreme immune response, which closely resembles rejection. The main difference is that it is quicker and more marked than rejection and then exhausts itself. This observation is unexpected and suggests possibilities for new treatments. Furthermore it questions the effectiveness of our present treatment for rejection of transplanted livers. We have already shown that some kinds of drugs given to prevent rejection in humans actually have the opposite effect in the animal model and prevent long-term acceptance of liver transplants. The aim of this work is to develop in our animal model a better way of treating human liver transplant patients. This will incorporate injection of donor white cells and treatment with drugs which promote the beneficial effects of these cells. We will also develop ways of testing the blood or the liver of the human liver transplant patients early after transplantation to find out whether the patient is accepting the liver or not. This means that we should be able to try this new treatment method in liver transplant patients once it has been optimised in the animal model.Read moreRead less
Morbidity and mortality secondary to liver disease is greatly increased in people co-infected with HIV and HBV compared to those infected with HBV alone. Mortality remains elevated even after treating both viruses. This project will investigate the mechanism of how HIV accelerates liver disease in patients co-infected with HBV. We hypothesize that this occurs by combined effects of HIV and HBV on inflammation in the liver. These studies could potentially lead to new treatments for liver disease.
Clinical Studies Of Novel Antiviral Therapies In Advanced Chronic Hepatitis B Virus Infection.
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
There is an urgent need to develop therapies for treating and preventing Hepatitis B antiviral resistance, particularly in patients with advanced liver disease. Investigator-initiated clinical studies will be performed to examine a) the most effective therapy for preventing antiviral resistance and Hepatitis B recurrence following liver transplantation and b) the effect of a novel Hepatitis B antiviral, tenofovir, on multi-resistant chronic Hepetatis B infection.
I am an immunologist investigating the interactions between the liver and the immune system in order to understand the tolerogenic property of this organ.
Hepatitis C Virus-specific Cellular Immune Responses Post-liver Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$470,233.00
Summary
Liver diseases associated with Hepatitis C, including liver failure and liver cancer, are now the leading indication for liver transplantation globally. However, the virus re-infects the new liver and eventually results in scarring and liver failure. This work aims to understand the role of the immune response to the virus in this liver damage, thus allowing modification of existing treatments and development of new therapies that will lead to improved outcomes for these individuals.
Cholestasis And Hepatocyte Injury In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$615,967.00
Summary
The aim of this project is to understand the consequences of long-term cholestasis or impaired bile excretion/flow on normal liver cells (hepatocytes) and to test whether specific bile acids can cause irreversible damage to hepatocytes leading to their transformation into pre-malignant cells and hepatocellular carcinoma (primary liver cancer). The results from this project will inform new strategies in screening, prevention and treatment of liver cancer in children and adults with cholestasis.
Significance Of Microparticles In The Pathogenesis Of Liver Ischemia Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$643,958.00
Summary
The overall aim of the project is to investigate the significance of microparticles in liver ischemia reperfusion injury (IRI). IRI causes damage to donor livers stored in preparation for liver transplantation. We postulate that microparticles released from the liver are critical in this form of injury. The expected outcomes are novel insights into liver IRI with the aim of developing new approaches to prevent liver damage during liver surgery, transplantation and shock.