Research offers hope of new treatments for liver damage ‘plague’

Millions of patients suffering from liver damage (cirrhosis) and failure may benefit from research by the Universities of Southampton and Edinburgh that could lead to new life-saving treatments. There is currently no cure for liver cirrhosis and a patient’s only hope of survival is to receive a liver transplant.

The Southampton scientists from the University’s Infection, Inflammation and Repair Division of the School of Medicine, in collaboration with colleagues from the University of Edinburgh and Cincinnati, USA have, for the first time, identified two separate populations of immune cells — macrophages — in the liver. One group of macrophages causes scarring to the liver, but the next wave of immune cells, produced only a few days later, change function to break down and reabsorb the scarring. These findings, published in the January edition of Journal of Clinical Investigation, will help doctors to understand the mechanisms by which the liver is damaged and repaired and may lead to future treatments.

Professor John Iredale of the University of Southampton said: ‘We are facing a huge increase in the numbers of patients with advanced liver fibrosis (scarring) and cirrhosis (end stage scarring of the liver). Currently we have no effective treatment for liver cirrhosis which is associated with internal bleeding, liver failure and the development of primary liver cancer. There is a huge imperative to develop new approaches to the treatment of liver scarring. Exciting insights such as these will inform the design of future therapies.’

Researcher Dr Jeremy Duffield of Edinburgh explained: ‘The links between the immune system, inflammation and scarring in the liver have not been well understood, and this has hindered progress in finding ways to prevent and repair liver damage. Now that we have shown how the macrophages work, we aim to find out how to create, activate and de-activate these cells to make them repair, rather than damage, liver tissue.’

He added: ‘Cirrhosis, commonly but not always caused by alcohol consumption, can lead to liver failure. At a time when outcomes for other diseases such as cancers and heart trouble have made dramatic gains, liver damage — described as the new plague of the 21st century — has yet to be understood and in turn to become treatable. More women in the UK now die of liver failure than do of cancer of the cervix.’

There has been a fourfold increase in the number of men aged 45–54 dying of cirrhosis since 1970 and a threefold increase in women of the same age group. Liver failure is also rapidly increasing in younger people with the deaths in the UK of 500 men and 300 women aged 25–44 in 2003.

Further research into macrophages is set to follow and scientists will explore the role of these immune-system cells in damage and repair to other organs, including the kidney.