A Study Of The Relationship Between Vitamin D Status And The Severity And Outcomes Of Chronic Non-cholestatic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Vitamin D deficiency is associated with common and severe conditions such as cancer, cardiovascular disease, autoimmune disease and diabetes. Recent studies suggest that vitamin D deficiency also worsens the severity and prognosis of chronic liver disease and that vitamin D replacement may improve outcomes. This research will further investigate the relationship of vitamin D deficiency to liver disease caused by the common conditions hepatitis B and C and non-alcoholic fatty liver disease and th ....Vitamin D deficiency is associated with common and severe conditions such as cancer, cardiovascular disease, autoimmune disease and diabetes. Recent studies suggest that vitamin D deficiency also worsens the severity and prognosis of chronic liver disease and that vitamin D replacement may improve outcomes. This research will further investigate the relationship of vitamin D deficiency to liver disease caused by the common conditions hepatitis B and C and non-alcoholic fatty liver disease and the impact of vitamin D replacement.Read moreRead less
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
Characterization Of ARL6IP5 In Hepatitis C-related Liver Cancer
Funder
National Health and Medical Research Council
Funding Amount
$505,283.00
Summary
The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hep ....The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hepatitis C leads to cancer.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.
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.
Population-level Epidemiological Trends In Hepatocellular Carcinoma In Queensland 1996 - 2010.
Funder
National Health and Medical Research Council
Funding Amount
$251,695.00
Summary
Incidence and mortality of hepatocellular carcinoma (HCC, the most common form of liver cancer) is increasing in Australia, driven by viral hepatitis infections. Disease burden is not defined in Queensland, particularly for Indigenous, migrant and regional and remote communities. Such factors may influence risk of viral hepatitis, access to treatment, and incidence and survival of HCC. Defining disease burdens will enable clinical programs targeted at groups most at risk in order to impact HCC t ....Incidence and mortality of hepatocellular carcinoma (HCC, the most common form of liver cancer) is increasing in Australia, driven by viral hepatitis infections. Disease burden is not defined in Queensland, particularly for Indigenous, migrant and regional and remote communities. Such factors may influence risk of viral hepatitis, access to treatment, and incidence and survival of HCC. Defining disease burdens will enable clinical programs targeted at groups most at risk in order to impact HCC trends.Read moreRead less
Inflammatory Pathways To Liver Fibrosis In Non-alcoholic And Alcoholic Steatohepatitis: Reversal By NLRP3 Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$572,857.00
Summary
Nonalcoholic steatohepatitis (NASH) caused by obesity and diabetes made worse by alcohol, leads to cirrhosis. There is no effective treatment. In mice with NASH, MCC950, a novel drug that blocks NLRP3 (molecule that incites inflammation) reverses liver inflammation and possibly scarring. This proposal will test what activates NLRP3 in NASH, and whether blocking it completely with MCC950 or a new lasting longer inhibitor will dissolve severe liver scarring, and scarring made worse by alcohol.
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