I am infectious disease physician undertaking research on natural history and therapeutic strategies in viral hepatitis, including acute hepatitis C, chronic hepatitis C and chronic hepatitis B. The hepatitis C therapeutic research has a particular focus
Evaluation Of Naturally Occurring Resistance To Direct Acting Antiviral Drugs (DAAs) In Individuals With Acute Hepatitis C Infection
Funder
National Health and Medical Research Council
Funding Amount
$333,778.00
Summary
Hepatitis C therapy in the future is likely to involve the use of Directly Acting Antivirals, which offer a better chance of treatment success and shorter treatment courses. The downside to these new agents is the possible development of drug resistance. Studies suggest that drug resistant strains may already exist in some individuals prior to treatment. This study plans to use sensitive methods to examine how common drug resistant strains are in untreated individuals with acute hepatitis C.
The renewal of my Practitioner Fellowship will continue to facilitate an expanding program of epidemiological and clinical research in viral hepatitis, with a primary focus on hepatitis C. New directions will include development of international clinical cohort and trials networks, particularly to characterise the natural history of early hepatitis C infection and evaluate hepatitis C therapuetic strategies for injecting drug users.
I am an infectious diseases physician and basic scientist interested in the immunopathogenesis of HIV and hepatitis B virus. My work focuses on HIV viral reservoirs and immune reconstitution and the adaptive immune response to hepatitis B virus.
Fine Positioning And Effector Function Of T Cells Recruited To The HCV Infected Liver
Funder
National Health and Medical Research Council
Funding Amount
$321,973.00
Summary
The majority of patients who become infected with hepatitis C virus (HCV) are unable to mount an effective immune response and clear the virus and therefore develop lifelong (chronic) infection. The persistence of virus in the liver of patients with chronic infection results in the recruitment of significant numbers of immune cells, notably T cells, from the bloodstream into the liver where they are involved in both viral control (but not viral clearance) and liver injury. The level of tissue in ....The majority of patients who become infected with hepatitis C virus (HCV) are unable to mount an effective immune response and clear the virus and therefore develop lifelong (chronic) infection. The persistence of virus in the liver of patients with chronic infection results in the recruitment of significant numbers of immune cells, notably T cells, from the bloodstream into the liver where they are involved in both viral control (but not viral clearance) and liver injury. The level of tissue injury observed and the speed of disease progression may be linked to the type of T cells recruited, their function, and their position in the liver. The aims of this project are to determine the factors involved in the fine positioning of T cells in the liver and establish a relationship between T cell recruitment, function, and progression of HCV disease in the liver.Read moreRead less
Suppression Of Immune Toll-like Receptor (TLR) Signaling By Hepatitis B E Antigen (HBeAg)
Funder
National Health and Medical Research Council
Funding Amount
$542,320.00
Summary
Hepatitis B virus (HBV) infection is a major world-wide health problem, which the current treatment strategies are not ideal. Therefore understanding how HBV inteacts with the immune system is of critical importance to developing intervention strategies to promote better health outcomes. This grant will develop our novel findings that a protein produced by HBV 'blinds' the host immune system by producing a protein that blocks the innate immune response to allow HBV to replicate unchallenged.
There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this proj ....There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this project is to investigate the liver disease caused by HBV in co-infected patients and the development of antiviral resistance due to the long-term treatment with lamivudine. We will develop a data base to monitor virological, biochemical and histological parameters for each of these co-infected patients. We will collate all information on these patients that are attending these various centres. This data base will be essential for monitoring the disease in patients with a poor immune system versus patients with a normal immune system. The HBV virus isolated from these patients will be characterised by sequence analysis. The sequence analysis of these viruses will be compared before and after treatment to determine any resistance markers that have developed. These resistant markers will be copied into an infectious clone using specialised molecular techniques. Clones containing these resistant markers will be analysed in the laboratory to determine the antiviral sensitivity to lamivudine and a number of new drugs against hepatitis B virus. This information will be important in treating patients that are co-infected with HBV and HIV and have already developed resistance to lamivudine.Read moreRead less
Hepatitis B Virus Immunity In Indigenous And At Risk Children Who Received Hepatitis B Vaccination In Infancy
Funder
National Health and Medical Research Council
Funding Amount
$213,762.00
Summary
Hepatitis B virus (HBV) is transmitted by blood exposure or sexual contact and infection can result in chronic liver disease and liver cancer. Since 2000 Hepatitis B virus immunisation has been recommended for all infants in Australia with the first dose given at birth. However, prior to routine universal immunisation, a selective immunisation strategy was used in Australia from 1986. This targeted infants considered at high risk of HBV infection because of high prevalence in their population of ....Hepatitis B virus (HBV) is transmitted by blood exposure or sexual contact and infection can result in chronic liver disease and liver cancer. Since 2000 Hepatitis B virus immunisation has been recommended for all infants in Australia with the first dose given at birth. However, prior to routine universal immunisation, a selective immunisation strategy was used in Australia from 1986. This targeted infants considered at high risk of HBV infection because of high prevalence in their population of origin, (including Aboriginal- Torres Strait Islanders) and infants whose mother was a HBV carrier. These children, among the first to be vaccinated, are now adolescents. There have been no long-term follow-up studies in Australia, and limited studies elsewhere, to assess the extent of breakthrough infection and persistence of immunity to Hepatitis B after vaccine at birth. As onset of sexual activity is associated with an increased exposure to hepatitis B infection, booster doses may be needed, especially in high-risk individuals. This study includes 2 high risk groups - young indigenous adults in the Northern Territory and young adults born to HBV carrier mothers in central Sydney. It will measure the number of children who have been infected with HBV or are chronic carriers, compared to pre immunisation data, and also the persisting level of immunity in children who were vaccinated against HBV as an infant. Children whose blood test indicates that they have low immunity will be given a booster dose of HBV vaccine and their immune response measured. A rise in hepatitis B antibody following booster vaccination indicates that you have immunological memory and is currently considered to show protection from natural hepatitis B infection. If clinically significant HBV infections are found to be rare and immunologic memory can be demonstrated, this would provide good evidence to support the argument that booster vaccine doses are not required in the Australian context.Read moreRead less
The development of vaccines and better treatments for HIV-AIDS and Hepatitis C are urgent global health priorities. This Program will undertake studies to better understand effective immunity against HIV and hepatitis C, allowing the rational design and testing of novel vaccines and treatments. The Program brings together a team of researchers with skills in basic virology and immunology with those providing expertise in translating findings in the laboratory into human clinical trials.
Immunological Changes During Pregnancy And The Impact On Viral Hepatitis Infection
Funder
National Health and Medical Research Council
Funding Amount
$353,355.00
Summary
Hepatitis B virus (HBV) can cause long term health problems particularly affecting the liver and can be passed from mother to baby. Despite the availability of a HBV vaccine babies can still become infected. During pregnancy there are changes in a woman’s immune system which may impact on HBV infection and make transmission to the baby more likely. This research aims to explore the changes in a woman’s immune system and the impact this has on risks for hepatitis and transmission to the baby.