Bulletin

Issue: April 2006

Research in Action

Possible new treatment for liver disease

Research at La Trobe University Bendigo may lead to more effective treatment of the liver disease, cholestasis.

A report of the research by the Head of the School of Pharmacy at Bendigo, Professor Kenn Raymond, and La Trobe Research Fellow, Dr Jiezhong Chen, appeared in the February 11-17 edition of the prestigious British medical research journal, The Lancet.

Cholestasis covers a number of conditions in which bile excretion from the liver is blocked from escaping from the body. It can occur either in the liver itself, called intrahepatic cholestasis, or in bile ducts, called extrahepatic cholestasis.

Prolonged cholestasis, the symptoms of which are jaundice, itching, fatigue and diarrhoea, can lead to liver failure and can be fatal. In very severe cases, the only treatment is a liver transplant.

Professor Raymond said the potentially more effective treatment involved the use of a combination of drugs that act as ‘receptors’ – proteins that occur on the surface of cells and assist the movement of bile salts from the liver.

He explained that the liver, one of the largest and most important organs in the human body, was responsible for utilising food and detoxifying drugs and also produced bile that helps digest fats. In certain liver diseases, including cholestasis, bile accumulates in the bloodstream.

‘In the past, treatment for cholestasis has been difficult and frequently ineffective because one of the older drugs commonly prescribed increased the metabolism of bile salts and so lowered their concentration in the body,’ Professor Raymond said.

He said that while he and Dr Chen, who is a medical doctor turned researcher, were investigating the metabolism of an anti-TB drug called rifamycin, they learned of the recent discovery overseas of two receptors in the liver.

Called pregnane X and farnesol X, they are involved in drug metabolic activities in the liver. ‘We believe that if we enhance their activity then the bile acids would be cleared more quickly from the body.’

Professor Raymond said that enhancement could be assisted by another recent development overseas – newly synthesised compounds called inducers which increase bile acid excretion.

‘We believe it would be very efficient if we could combine the old drugs that increase the metabolism with the new inducers. Such a combination may possibly lead to a cure for cholestasis.’

Professor Raymond emphasised that as yet the results of the research were theoretical and the theory needed to be clinically evaluated. This is planned in conjunction with a Melbourne teaching hospital.

Professor Raymond said it was an honour to have the research published in The Lancet.

‘Few papers by academics are published in this prestigious journal which provides an opportunity to promote to other research workers and hepatologists world wide.’