So far, there have been two main approaches. One of these involves passing the patient's blood through large tubes containing granules of charcoal or other adsorbents. The granules are coated with a polymer that provides a semi-permeable membrane. The membrane has pores of different sizes that allow relatively small toxic substances, but not blood cells or large molecules such as proteins, to pass across it and become trapped by the adsorbents - thereby removing them from the blood. The membrane also acts as a barrier to stop any fragments of the granules entering the blood. These devices are mainly geared to reproducing the liver's detoxifying functions.

The second approach is to pass the blood through numerous fine hollow-fibre tubes made of semi-permeable membranes, which are contained in canisters filled with living human or animal liver cells. The liver cells are on the outside of the fibres and cannot pass through the membranes into the blood, but the membranes can allow quite large molecules such as proteins to pass back and forth between the blood and the cells - much as happens normally within the liver itself. The idea here is to get the cells to perform most of both the detoxifying and manufacturing functions of the normal liver.

The main problems with these devices are ones of engineering and 'biocompatibility'. They need to be constructed in a way, and from the right materials, such that they do what they are intended to do without damaging the patient's blood cells or removing beneficial substances from the blood. Two additional problems with the devices using living liver cells are: how to get sufficient of these cells into the systems to be really useful, and how to keep the cells alive during use. Progress is being made and clinical trials are currently underway with several of these devices, but none is yet at the stage where it can be used routinely.

Research on AIH.
Research on AIH over the past 30 years has mainly addressed the following:

1. Understanding the variability of the disease between different people who are affected.
2. Understanding the potential complications and how to prevent/treat them.
3. Investigating new treatment strategies, especially for people who do not respond to standard therapy or develop complications with this.
4. How does the immune system become activated in such a way as to attack the body's own tissues (liver), and to such an extent ?
5. How is the liver actually damaged ?
6. What are the genetic defects in the immune system that underlie the development of AIH ?
7. How can tests for diagnosing AIH and monitoring the response to treatment be improved, and can such tests provide clues to the mechanisms involved in the disease ?

Research into the clinical aspects of AIH, i.e. how to diagnose and treat it (points 1-3 above), has been going on continuously and a great deal is now known. Currently, most of the research in this area is being devoted to looking for new ways of treating it.

Most of the work relating to points 4 and 5 above was done in the 1970s and 1980s. Investigators learned a lot about these issues but then seemed to hit a brick wall. This is because there is no known animal that spontaneously develops AIH and most of that type of research had therefore to be done with the patients themselves. But, partly for technical reasons and also because the disease varies so much between patients, it has been very difficult to make further progress. There have been several attempts in the past to develop models of AIH in mice, rats or rabbits. Although these experiments have provided some information, none of the models has been entirely satisfactory because the animals do not have the genetic defects that lead to development of AIH. So this type of research has more or less ground to a halt.

At present, much of the research effort is aimed at trying to identify the genetic defects in the immune system that make people susceptible to developing AIH (point 6). This is painstaking research because it is clear that there are several defects which probably act together, and finding the correct combination of defects is very difficult. The other major area of research relates to identifying the liver proteins with which some of the autoantibodies in patients' blood react (point 7). This is partly to try to develop more specific tests for AIH but, more importantly, by studying these proteins researchers may be able to find out more about how the liver damage occurs.

"The increasing number of middle-aged patients with chronic liver disease caused by heavy drinking is forcing doctors to look at new ways of saving their lives.

A pioneering trial to help seriously ill people will begin this month, using the patient's own cells to regenerate the organ. By injecting patients with their own stem cells, the basic 'building blocks' for all kinds of cells, doctors hope that the liver can regrow itself to a point where the organ starts to work again.

The trial is experimental, but follows other work which shows that stem cells have helped patients with heart failure. The dire shortage of donor organs for transplant has encouraged the specialists to think of new ways of helping patients who otherwise have a very bleak future.

One in 20 people in Britain is now dependent on alcohol and a similar number are at serious risk of liver disease. Physicians and government experts have warned that alcohol-related harm - severe liver disease and injuries caused by drink-related violence - are on the rise as the nation's drinking habits become heavier.

Deaths from liver disease in patients under 50 have risen sevenfold in the past 30 years and surgeons have warned they are seeing a growing number of patients with cirrhosis of the liver, a condition where the healthy liver tissue is gradually replaced by scarred, useless tissue. The disease is insidious, because apparently healthy people may have it without knowing and the first signs do not occur until a late stage of the disease.

When alcohol is drunk, it is quickly absorbed and passes in the bloodstream to the liver, where it can cause excessive fat to be deposited within the liver cells. Between 20 and 30 per cent of those who drink heavily beyond the initial stages of liver damage will develop alcoholic hepatitis, a condition which can be fatal. A smaller number, about 10 per cent, go on to develop cirrhosis. Although alcohol is the leading cause of cirrhosis, it can also be brought on by forms of hepatitis or by some toxic chemicals. Scientists at Imperial College London believe stem cell therapy holds out enormous hope for those who need new organs. Professor Nagy Habib, head of liver surgery at London's Hammersmith Hospital, who is running the trial, said: 'The liver is a wonderful organ in the way it can regenerate itself, but if there is a lot of damage it stops functioning properly. If we can get 15 to 20 per cent of the organ regenerated, then that is enough to really improve the patient's condition. These cells seem to have the fantastic ability to become whatever is needed in order to repair the damage.'

By injecting the patient's own stem cells, taken from their blood, directly into the bloodstream, the researchers hope they may be able to improve the function of the liver by getting the stem cells to repopulate the liver.

The procedure, known as leukapheris, involves taking blood from a patient and then separating it into its component parts. The stem cells are taken from the white blood cells, while the red blood cells are returned to the body through the arm. Habib and his team then inject the stem cells into the hepatic artery, the vessel which goes into the liver.

Habib believes they have to look at all the potential cures. There are about 700 liver transplants in the UK each year, but 7,500 die annually from liver disease. Alcohol is the major reason for a transplant, followed by the virus hepatitis C. 'The demand for a transplant has really risen,' said Habib. 'We don't have the equivalent of a kidney dialysis machine for these patients, so unfortunately most of them will die while waiting for an organ.'

It is not yet known how many stem cells may be needed for the trial to succeed. The worse the patient's liver function, the more cells may be necessary. 'If you can provide 1 per cent of liver cell mass, and then allow that 1 per cent to grow over a three-month period, it's possible that the liver will have enough healthy cells to behave properly, and start to produce what it needs,' said Habib.

Like many specialists, he worries that people do not understand the damage that can be done by heavy, prolonged drinking. 'If people could see what life was like in the final stages of liver failure, they might think seriously about giving up at a much earlier point,' he said. 'The liver is a very forgiving organ, but there's a limit to how much alcohol it can process before the damage sets in.'

Children's Liver Disease Research

British Liver Trust Research