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Hepatitis C and the Immune System

July 28, 2006

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Australian researchers have uncovered a link between hepatitis C infection and an individual’s immune system. By examining this virus on a genetic level, new understanding about hepatitis C’s ability to mutate and persevere in certain people brings us closer to the development of a successful vaccine.

WA leads bid for hep-C cure

by Louise Pemble

PERTH researchers are closer to explaining why some people can fight off the Hepatitis C virus while others succumb to the potentially deadly infection.

Their findings could pave the way for a vaccine against hepatitis C infection, which affects more than 210,000 Australians and 200 million people worldwide.

The team, based at the Centre for Clinical Immunology and Biomedical Statistics at Royal Perth Hospital, already has made headway in understanding the interplay between the individual and the virus at the genetic level, and how this influences the body’s immune response to the virus.

This followed groundbreaking work headed by the centre’s director, Simon Mallal, whose study of Perth HIV sufferers was the first in the world to show that patients had different forms of the virus as it tailored itself to individual immune responses and different populations.

Prof Mallal was awarded a $US9.8 million grant by the Bill and Melinda Gates Foundation to create state-of-the-art databases recording the genetics of the virus and people in key populations around the world.

Prof Mallal said it was on the back of those findings that he shifted attention to hepatitis C because the jlbehaviour of the virus was poorly understood, even though it affected so many Australians.

His team worked on a hunch that hepatitis C would behave in the same way as the HIV virus, which constantly mutated to evade a knockout blow by the body’s natural defence, the immune system.

Researcher Silvana Gaudieri said the HIV research had been crucial in laying the groundwork for the hepatitis C study, though there were key differences.

“Unlike HIV, of those individuals exposed to hepatitis C, about 30 per cent resolve their infection without the need for therapy,” she said.

“For those who become chronically infected, many suffer liver disease, including cirrhosis, and require liver transplants.

“In essence, the hepatitis C epidemic is a time bomb within the community, with a likely high burden on the health system in the years to come.”

The research team has just recruited new subjects who are ideal candidates for answering many of the puzzles surrounding hepatitis C.

With funding from the Haemophilia Foundation of Australia, a study now involves West Australians with haemophilia, who will provide a unique nts cohort nte opportunity for discoveries in this area. Many people with haemophilia were exposed to the virus through blood donation before widespread screening was introduced.

Throughout the ’70s and ’80s, they were given multiple infusions of blood, including plasma infected with hepatitis C, but not all succumbed to the virus.

This made them ideal candidates for study because they had been exposed to many different strains of the virus over time, according to trial investigator Michaela Lucas.

Dr Lucas, working in collaboration with colleagues from the Haemophilia Centre of WA headed by Associate Professor Ross Baker and from CCIBS including Dr Katja Pfafferott, said they offered a rare opportunity to find out why some resolved infection while others did not.

“Work published on HIV showed that an individual’s ability to fight the virus leaves an imprint on the virus,” she said.

“That’s why the virus is always changing to try to evade the body’s immune response.

“We were looking for information about how the hepatitis C virus interacts with an individual to resolve why the progress of the disease can differ markedly in each person.”

The team is faced with many unsolved questions about hepatitis C. For instance, some people can be infected with hepatitis C for 10 to 20 years with few or no clinical symptoms, while others get liver disease quite rapidly.

Some of the factors that influence the disease’s progress are sex, age, alcohol consumption and the presence of another infection, such as HIV.

Researchers turned their attention to which parts of the virus could change to escape or “hide” from the body’s immune response.

Two factors were crucial – the way the body fought the virus and the type of virus.
The study focuses on the immune system’s specialised white blood cells, or T-cells, that are the key to fighting the virus.

As with HIV, a better understanding of how the virus changes as it moves through a population will help develop designs for vaccines, though Dr Lucas stressed that this was early stage research, rather than a vaccine trial.

Hepatitis C is potentially curable, but many patients do not respond to treatment.
Dr Lucas, who has previously worked with leading hepatitis C researcher Dr Paul Klenerman at Oxford University, said the Perth findings would help explain the role mutation of the virus played in escaping an individual’s immune response.

The study, which is now in its second year, has also been supported by the National Health and Medical Research Council and from this month, funding will be added by the Haemophilia Foundation to specifically investigate a person’s immune response to multiple strains of HCV.

copyright 2006 The Sunday Times, News Limited

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Posted by The Editors at Hepatitis Central on July 28, 2006

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