Host Determinants Of Hepatitis C-associated Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$610,376.00
Summary
Hepatitis C virus (HCV) infection is a major cause of liver disease and associated deaths in Australia. HCV infection leads to progressive liver failure and may be associated with the development of liver cancer. Currently there are an estimated 220,000 people in Australia living with HCV infection, and by 2020 it is estimated that this number will treble. There is now considerable evidence to indicate that the effect of HCV on the liver is due to ongoing immune activity and the build up of fat ....Hepatitis C virus (HCV) infection is a major cause of liver disease and associated deaths in Australia. HCV infection leads to progressive liver failure and may be associated with the development of liver cancer. Currently there are an estimated 220,000 people in Australia living with HCV infection, and by 2020 it is estimated that this number will treble. There is now considerable evidence to indicate that the effect of HCV on the liver is due to ongoing immune activity and the build up of fat (steatosis) in the liver. This results in the production of biochemical products that lead to tissue damage and to eventual destruction of the liver. Further evidence has recently emerged to suggest that the susceptibility to, and outcome of HCV infection may be influenced by genetic variation in the infected population. The chief investigators on this project have established the best characterised clinical cohort of HCV infected persons worldwide. Further, they have developed considerable expertise in the field of genetics, i.e. the analysis of genes that influence the host's response to an illness. Using this information and expertise, we propose in the present study to analyse in detail the host genetic factors that contribute to variations in the response to HCV, and its correlation with HCV-associated liver damage. This data could allow the development of better patient care strategies and the design of novel therapeutics.Read moreRead less
Screening For Chlamydia Trachomatis With Routine Pap Smears In General Practice: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$350,500.00
Summary
Genital chlamydia infection is the most commonly reported infectious disease in Australia. Notifications have increased three fold since 1995; five-fold in the ACT and surveillance data underestimate the true incidence of the disease in the community. Chlamydia is associated with immediate morbidity in men and women including urethritis, epididymo-orchitis, cervicitis, and pelvic pain and long-term complications including pelvic inflammatory disease, ectopic pregnancy and tubal factor infertilit ....Genital chlamydia infection is the most commonly reported infectious disease in Australia. Notifications have increased three fold since 1995; five-fold in the ACT and surveillance data underestimate the true incidence of the disease in the community. Chlamydia is associated with immediate morbidity in men and women including urethritis, epididymo-orchitis, cervicitis, and pelvic pain and long-term complications including pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility. The economic costs of Chlamydial infection in Australia have been estimated to be as high as $160 million each year. In the ACT 73.8% of chlamydial infections occur in the 20-40 year old group. Between 60 and 70% of women in this age range participate in Pap screening every two years. While targeted screening for Chlamydia in women is effective in the US, there are few studies that investigate its value in an Australian setting. In this randomised controlled clinical trial we aim to test the novel hypothesis that the routine offer of chlamydia testing to women between 20 and 40 years who undergo Pap screening significantly increases the detection of Chlamydia in that population. This is the first randomised-controlled trial of its type and is an extension of a current non-randomised pilot study of linked Chlamydia-Pap screening in the primary care setting. The aim is to determine if the program can be incorporated more widely in the ACT. The study will: Measure the impact of linked chlamydia-Pap screening on chlamydia screening participation rates More accurately determine the epidemiology of genital chlamydial infection in this age group and social setting; Undertake an economic evaluation of this approach; Determine if promoting the Pap smear as an opportunity for chlamydial screening increases the uptake of Pap screening in younger women Aid in the development of a National Chlamydia Screening strategyRead moreRead less
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.
Hepatitis C virus (HCV), the main cause of of post-transfusion and community -acquired non-A, non-B hepatitis, infects approximately 170 million humans world-wide with some 135,000 infections in Australia alone. HCV is hyper-endemic in intravenous blood users with typical prevalence rates of 60-70%. About 75-80% of infected individuals develop a chronic infection, usually resulting in recurrent, progressively worsening liver damage. Cirrhosis develops in 10-20% of chronic cases while 1-5% of chr ....Hepatitis C virus (HCV), the main cause of of post-transfusion and community -acquired non-A, non-B hepatitis, infects approximately 170 million humans world-wide with some 135,000 infections in Australia alone. HCV is hyper-endemic in intravenous blood users with typical prevalence rates of 60-70%. About 75-80% of infected individuals develop a chronic infection, usually resulting in recurrent, progressively worsening liver damage. Cirrhosis develops in 10-20% of chronic cases while 1-5% of chronic carriers develop liver cancer. Development of an effective vaccine is complicated due to the highly variable nature of the virus. Approved therapies include alpha-interferon and alpha interferon-ribavirin combinations but these treatments induce efficacious responses in only 20-30% of patients and often have severe side-effects. It is assumed that after attachment of HCV to the cell surface, the virus is internalised by the cell and undergoes fusion with a cellular compartment referred to as an endosome. The low pH environment of the endosome is presumed to trigger viral fusion via its cell surface glycoproteins and empties the replication machinery of the virus into the cell. No reliable systems for the propagation of HCV are available thereby limiting studies into the mechanisms of how HCV infects cells and the development of vaccines. Recently a cell surface molecule, CD81, was identified as a possible receptor for the attachment of HCV to susceptible cells. Our aim is to 1) develop model systems for studying HCV entry and fusion and 2) further characterise the interaction of the HCV glycoproteins with CD81 with the goal of obtaining a three-dimersional structure of the interaction . These studies will address the fundamental questions of how HCV enters cells leading new avenues for the design of inhibitors of HCV entry.Read moreRead less