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Inflammatory Mediators Of Liver Injury In Chronic Hepatitis C
Funder
National Health and Medical Research Council
Funding Amount
$349,336.00
Summary
Presently, liver disease from chronic hepatitis C and obesity represents a major health problem. Overall, approximately 50% of Australians with chronic hepatitis C are obese and these patients are at significantly increased risk of rapidly progressing to liver failure. It is now recognized that fat derived factors play an important role in regulating inflammatory responses. This grant proposal aims to gain insight into how liver and fat derived inflammatory factors interact to promote increased ....Presently, liver disease from chronic hepatitis C and obesity represents a major health problem. Overall, approximately 50% of Australians with chronic hepatitis C are obese and these patients are at significantly increased risk of rapidly progressing to liver failure. It is now recognized that fat derived factors play an important role in regulating inflammatory responses. This grant proposal aims to gain insight into how liver and fat derived inflammatory factors interact to promote increased liver damage in chronic hepatitis C and obesity.Read moreRead less
Virological Determinants Of Drug Resistance In Real-world Patients With Chronic HCV Infection
Funder
National Health and Medical Research Council
Funding Amount
$550,718.00
Summary
New treatments for hepatitis C virus (HCV) infection are emerging. These drugs directly target key events in the viral life cycle. While these drugs are effective, the ability of HCV to mutate means that drug resistance can arise, leading to treatment failure. This is most likely in patients who do not respond to interferon-based therapy. This proposal will use new, highly sensitive sequencing approaches to identify the viral mutations and evolutionary pathways that lead to drug resistance.
Characterisation Of Anti-HBs Responses In Patients Undergoing Functional Hepatitis B Cure: Implication For Future Therapies
Funder
National Health and Medical Research Council
Funding Amount
$723,649.00
Summary
The hepatitis B virus causes liver cirrhosis and liver cancer. There is no cure for hepatitis B. However, a small number of patients can naturally rid themselves of the virus. We have identified 14 of these individuals and discovered that they have a unique immune response that is responsible for these “natural” cures. We plan to characterise this immune response and turn it into a therapeutic vaccine which can be used to cure patients who are still chronically infected.
Studies On The Pathogenesis And Treatment Outcomes Of Chronic Viral Hepatitis
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
The global impact of hepatitis B and hepatitis C has recently been recognized by the World Health Organization. The Fellowship will support a research program that will use new technologies to answer a number of important questions concerning the pathogenesis of viral hepatitis B and C, interferon treatment response for HCV, and antiviral drug resistance. The outcomes of the research will be timely, clinically relevant, and of great interest to the international community. The ultimate goal is t ....The global impact of hepatitis B and hepatitis C has recently been recognized by the World Health Organization. The Fellowship will support a research program that will use new technologies to answer a number of important questions concerning the pathogenesis of viral hepatitis B and C, interferon treatment response for HCV, and antiviral drug resistance. The outcomes of the research will be timely, clinically relevant, and of great interest to the international community. The ultimate goal is to improve clinical outcomes for patients.Read moreRead less
ANTIVIRAL DRUG RESISTANT HBV: PATHOGENIC AND ONCOGENIC SIGNIFICANCE OF THE ALTERED VIRAL ENVELOPE
Funder
National Health and Medical Research Council
Funding Amount
$509,284.00
Summary
We aim to investigate the consequences of long-term therapy for hepatitis B on liver cancer progression. We propose that antiviral therapy is associated with persistent expression and accumulation of potentially oncogenic surface proteins in the liver. This can dramatically alter the viral lifecycle, particularly the HBsAg secretion pathway, which can cause serious effects in the host hepatocyte biology, including promoting pathways to tumour formation.
Hepatitis C affects a quarter of a million Australians, causing insidious but progressive liver disease which culminates in liver failure or cancer. There is no vaccine and prevention programs have limited effectiveness, but new antiviral therapies now offer high rates of cure. This Program will evaluate strategies to improve the health of those affected and prevent new infections by better understanding of the virus and the body’s immune response, including scarring and liver cancer formation.
The Role Of Cyp2e1, Alcohol And HCV In Modulation Of Hepatocyte Homeostasis HCV Replication And Resistance To Interferon
Funder
National Health and Medical Research Council
Funding Amount
$455,520.00
Summary
Liver disease caused by alcohol consumption and hepatitis C virus (HCV) infection are major national health problems. Liver disease caused by HCV is greatly accelerated by alcohol consumption, however, the connection between the biochemical events initiated by alcohol, HCV and inflammatory pathways resulting in liver disease are not well understood. Preliminary studies have identified a link between an important alcohol-metabolising enzyme, Cyp2e1, HCV replication, oxidative stress and a powerfu ....Liver disease caused by alcohol consumption and hepatitis C virus (HCV) infection are major national health problems. Liver disease caused by HCV is greatly accelerated by alcohol consumption, however, the connection between the biochemical events initiated by alcohol, HCV and inflammatory pathways resulting in liver disease are not well understood. Preliminary studies have identified a link between an important alcohol-metabolising enzyme, Cyp2e1, HCV replication, oxidative stress and a powerful mediator of liver injury called tumour necrosis factor alpha. Furthermore we have shown that alcohol metabolism by Cyp2e1 results in an increase in HCV replication and negatively impacts on the anti-viral action of interferon. The studies contained within this proposal aim to build on these exciting new insights by attempting to identify new mediators and mechanisms of liver disease as a consequence of Cyp2e1 expression, alcohol and HCV replication. We will also examine the molecular mechanisms by which alcohol potentiates HCV replication. These studies will assist in developing therapeutic strategies that will benefit alcohol- and HCV-related liver disease.Read moreRead less