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Where immunology meets liver disease - Professor Geoff McCaughan reflects on his career as a hepatologist

Interview by Marge
Med J Aust
Published online: 15 October 2012

Professor Geoff McCaughan is one of Australia’s leading hepatologists. He works in both clinical medicine and laboratory-based research at Sydney’s Royal Prince Alfred Hospital (RPA), where he is head of the Liver Immunobiology Group at the Centenary Institute, and director of the AW Morrow Gastroenterology and Liver Centre. He is also co-director of the Australian National Liver Transplantation Unit.

My interest in liver disease stemmed from when I was a medical student in the early 1970s and did a term in southern India. The head of the medical unit at the hospital where I was based said: “You’re from Royal Prince Alfred Hospital. They’re famous for autoimmune liver disease”. He asked me to give a seminar so I went to the library and learnt that RPA’s work with autoimmune liver disease had defined the natural history and the treatment for the condition, which occurred in young people, particularly women, and had a high mortality rate. I was also drawn to the area because I had a fundamental bias to immunology in my undergraduate years.

When I came back to Prince Alfred Hospital, I worked as an intern under Professor Ruthven Blackburn, who was a pioneer of autoimmune liver disease. At the end of my residency, I had to decide on a specialty — immunology or gastroenterology. Clinically, I was attracted to liver disease because it seemed to be more challenging (HIV did not exist). I looked after a lot of hepatology patients in my intern and residency years under Professor Blackburn. I decided to do clinical training in gastroenterology but with a major interest in hepatology. I wrote my first papers on liver cancer and hepatitis B when I was a registrar training under Professor Neil Gallagher.

After my advanced training, I did a PhD in cellular immunology at the University of Sydney under Professor Tony Basten and then a postdoctorate in molecular immunology in Oxford under the world famous immunologist, the late Professor Alan Williams. When I came back to Australia in 1986, I was appointed staff specialist in hepatology at RPA just as the Australian National Liver Transplantation Unit was established at the hospital. This was the perfect job for me because I had scientific research training in immunology and a clinical interest in liver disease.

Professors Blackburn and Gallagher were my main clinical mentors when I was training. They were both eccentric and challenging intellects. It was hard to have a straight conversation with them; you always had to be on your toes. Tony Basten and Alan Williams instilled in me the excitement and necessary rigour to do good laboratory research.

My major research in the laboratory has been identifying molecules that are involved in damaging the liver through various diseases. We were the first to clone the human gene for the enzyme DPP4, and we’ve cloned other genes in the family. Associate Professor Mark Gorrell is using this enzyme for therapies in diabetes, and it’s one of the major targets for new therapeutics in diabetes and fatty liver disease. We also did the first gene array experiments in human liver diseases. I have also had the privilege to collaborate with pure immunologists, such as Dr Patrick Bertolino and Dr Alex Bishop, to understand liver transplant tolerance.

My career has been rewarding in both clinical medicine and basic research. At the clinical level, when I was training 25–30 years ago, people died in front of me from the complications of chronic liver disease, cirrhosis and liver cancer. Now, liver transplantation not only has the potential to rescue those patients from certain death, it transforms their lives and their family’s lives. I still find that remarkable, and I see it every week. But it is challenging trying to keep patients alive while they wait for a liver transplant. Australia’s organ donation rate is 24th in the world. In the lab, I continue to be turned on by new discoveries — finding a molecule and working out how it functions, or coming up with an unusual result and asking why. I enjoy working clinically and scientifically with young people. They keep me stimulated and challenged.

One of the great changes in the near future will be new and emerging treatments for hepatitis C. The challenge will be to deliver these therapies to 10 or 100 times the number of patients we’re treating now. We will have to deliver treatment in the community, not in hospitals or specialists’ rooms. It will also require federal and state governments to work together to ensure these drugs reach the disadvantaged communities in which hepatitis C is more common. Hepatologists such as myself will return to just looking after advanced liver disease and liver cancer — just like the old days!

My best advice to a young doctor interested in a career in hepatology is to maximise your training. I was lucky and fell into a job at RPA that suited me perfectly, but if I hadn’t positioned myself with my clinical training, PhD and postdoctorate, I wouldn’t have got the job.

At work I try to make sure that people have a high work ethic but also enjoy themselves and that there is humour, even in adversity. This remains an important part of my philosophy and I try to instil it in people who do ward rounds with me, and scientists who make amazing discoveries.

  • Interview by Marge


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