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
Implementing And Enhancing Evidence-based Research And Practice In Hepatology
Funder
National Health and Medical Research Council
Funding Amount
$569,219.00
Summary
The overall aim of this proposal is to tackle unmet challenges in liver disease research. This will be achieved through (a) Population level programs to deliver new treatments for patients with hepatitis C; (b) Developing integrated care models to treat hepatitis B; (c) Developing population-level programs for liver cancer control; and (d) Identification of patients at risk of severe liver disease through understanding the genetic basis of disease progression.
Studies Of The Role Of The Hepatocyte In The Response To HCV Infection
Funder
National Health and Medical Research Council
Funding Amount
$513,294.00
Summary
Infection with hepatitis C (HCV) affects 120 million individuals worldwide, and over 200,000 in Australia. HCV-related liver disease is the most common indication for liver transplantation in Australia and rates of HCV-related liver failure and hepatocellular cancer are predicted to increase as the HCV population ages. A new test for the IL28B gene, has shown to be the strongest predictor of cure after treatment. The mechanism of this association is unknown and is the subject of this grant.
The Effect Of IL28B Haplotype On Hepatitis C Virus Infection And Treatment Response
Funder
National Health and Medical Research Council
Funding Amount
$525,576.00
Summary
About 3% of the world population is currently infected with hepatitis C virus (HCV). Most have chronic infection with a high risk for progressive liver fibrosis and subsequent liver cirrhosis and hepatocellular carcinoma. We have recently demonstrated genetic variants of the IL28B gene predict viral clearance with and without treatment after HCV infection. Determining why will impact on the development of new therapies, optimise use of current therapies, and identify patients who may respond to ....About 3% of the world population is currently infected with hepatitis C virus (HCV). Most have chronic infection with a high risk for progressive liver fibrosis and subsequent liver cirrhosis and hepatocellular carcinoma. We have recently demonstrated genetic variants of the IL28B gene predict viral clearance with and without treatment after HCV infection. Determining why will impact on the development of new therapies, optimise use of current therapies, and identify patients who may respond to alternative therapies.Read moreRead less
The Role Of Endocannabinoids In Chronic Hepatitis C
Funder
National Health and Medical Research Council
Funding Amount
$563,002.00
Summary
Hormones related to cannabis help to regulate fat stores in the human body. CB1 antagonists are a new class of drugs that block these hormones and are being tested for the treatment of obesity and fatty liver. We discovered that Hepatitis C makes the liver more sensitive to these hormones, helping the hepatitis C virus to replicate. This project will determine the mechanisms by which CB1 antagonists prevent hepatitis C virus replication and their potential as a novel therapy for this disease.
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.
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
Liver Lipotoxicity And NASH: Mechanistic Roles Of Free Cholesterol, Saturated FFA, JNK1 And TLR4
Funder
National Health and Medical Research Council
Funding Amount
$429,712.00
Summary
Non-alcoholic fatty liver disease (NAFLD) occurs in overweight people, diabetes and with high blood pressure and raised cholesterol. This research is about how cholesterol in liver cells interacts with long chain fatty acids to cause injury and inflammation (steatohepatitis, NASH) in NAFLD.