The role of the innate immune system in combating hepatitis – Associate Professor Kumar Visvanathan and Professor Alex Thompson

Almost half a million Australians are living with chronic viral hepatitis, but pregnant women with the infection face particular risks, as do their unborn babies.

D4D_5014 copy_blogIt’s a problem being addressed by two of St Vincent’s leading specialists – Clinical Director of Medicine and Emergency Services Associate Professor at the University of Melbourne, Kumar Visvanathan, who specialises in infectious diseases, and Professor Alex Thompson, Director of Gastroenterology and Professorial Fellow at the University of Melbourne.

Together they are working on a range of research projects to investigate the immune system’s response to, and develop new treatments for, chronic hepatitis B and C.

Chronic hepatitis can lead to cirrhosis, liver failure and liver cancer. It’s the leading cause of liver transplants in Australia, and liver cancer is the fastest growing cause of cancer-related deaths in this country.

One area of their research is trying to understand why pregnant women with hepatitis can have a flare-up in their condition. A/Prof Visvanathan says the research is focusing on what’s triggering the pregnant women’s immune system to react that way.

“The flare causes an inflamed liver, which can be severe and worsen liver damage. The teamis looking at ways to predict which patients will flare.”

“If we can determine what is making them flare, we will know which patients should be on anti-viral drugs during pregnancy and which patients can get off the drugs without incident,” he says.

About 30 per cent of pregnant patients with hepatitis B are at risk of a rapid escalation in their condition in the first few weeks after they have their baby.

Another study is looking at preventing mother–baby transmission of hepatitis B infection by treating patients with antiviral therapy late in pregnancy.

“In some parts of Melbourne we are seeing prevalence rates as high as 7 to 8 per cent, which rivals the rates in mainland China. This is an enormous health issue that we are starting to address with antiviral treatment during pregnancy to prevent vertical transmission of the HBV to the baby,” A/Prof Visvanathan says.

Prof Thompson’s postdoctoral work at Duke University involved a genome-wide association study that discovered the link between a particular gene (IL28B) and the body’s response to interferon-based treatment. In their current research, funded by grants from the NHMRC and the Australian Centre for HIV and Hepatitis, the team is trying to understand how that link works in hepatitis C treatment.

Prof Thompson says that this link has led to a standard test to determine the best course of treatment for hepatitis C patients who are considering antiviral therapy.

“However, we don’t understand why this occurs – but we are sure the innate immune system plays an important role,” he says. Two PhD candidates, Dr Jacinta Holmes and Dr SweeLin Chen Yi Mei, are working on this problem.

A/Prof Visvanathan says the research asks two central questions – “Why is this happening to our patients?’ and ‘How can we use this knowledge to improve the care of our patients?  “We want to clearly define the role of the innate immune system in diseases so we can develop new therapeutics and biomarkers,” he says.

Both researchers run a number of clinical trials evaluating new therapies for hepatitis C and hepatitis B in partnership with industry.

“The new antiviral agents in development for hepatitis C are incredibly exciting, and represent a major medical breakthrough,” says Prof Thompson.

“Treatment has shifted from toxic drugs that had to be injected once per week for a year – which achieved cure rates of only 50 per cent – to a simple, daily pill that can cure more than 95 per cent of patients in eight to twelve weeks.  This has been a very rewarding experience for us, but far more so for our patients.”

The team believes that it may even be possible in the future to eradicate hepatitis C from the Australian community. If the transmission of hepatitis C can be interrupted, the prevalence of the disease will dramatically decrease over the next two decades.

“These are very exciting times in this research area,” Prof Thompson says.

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