The Problem
Every year in the UK thousands of people die of liver failure, and worldwide this affects millions.
Liver failure is a catastrophic disaster. Without a functioning liver death is inevitable.
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The balance of the body's chemistry cannot be maintained, and all other organs begin to fail
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The kidneys stop working
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Blood ceases to clot, often leading to internal haemorrhage
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The brain stops working, leading to coma and death
The Unique Opportunity
YET the liver, unlike other organs, has a remarkable capacity to RE-GROW after acute damage - given time...
'Before' and 'after' surgery - illustrates how the normal fragment of liver (shown in pink) can grow to restore normal functions.
The Solution
Thus, the solution our funds support is a Bio-Artificial Liver Machine, that temporarily replaces liver function, giving the liver those critical few days necessary to heal itself.
The difficulty in replacing the liver artificially, and the reason why this solution does not already exist, is that, unlike most other organs which have a sole function, the liver performs a myriad of duties to keep us alive, which cannot simply be replaced with a single mechanical operation.
An artificial liver must perform all of the liver functions. The only feasible approach is to use liver cells themselves.
With this in mind, the researchers we support have established a new way of growing human liver cells outside the body. This has overcome the loss of performance when liver cells are kept in culture outside the body, one of the major problems of establishing an artificial liver. With this new technique, a liver cell can perform many of the functions as well in culture as it would in the liver itself. With this new method clinicians will be able to 'clean up' and improve the quality of 'sick' blood.
In the near future we envisage that a patient with liver failure will be treated with a Bioartifical Liver Machine, probably for several days, taking their blood with plastic tubes, passing the blood plasma over a culture of liver cells, and returning the 'cleaned' blood to the patient.
Diseases of the Liver
Hepatocellular Carcinoma / Cancer of the Liver
Cancers that develop in a particular organ are primary to that organ whereas metastases are cancers that have come from another organ and taken root in a new place. Liver cancers can be primary or secondary (metastatic), from cancers in other parts of the body including the lungs, gut, spleen, breast and ovaries. Similarly cancer of the liver can also spread to other parts of the body. Primary Hepatocellular cancers are less common than metastatic or secondary liver cancers.
Cancer of the liver can arise from the cells that make up the liver (hepatocytes) as well as the cells that line the bile ducts (cholangiocytes).
Cancer of the liver can be the end stage of a variety of diseases and processes that take place within the liver including:
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Alcoholic Liver disease
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Cirrhosis and scaring of the liver
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Hepatitis (inflammation of the liver)
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Fatty liver
Liver Cancer is said to be multifactorial; whether or not one goes on to develop the disease is a result of the risks that are associated with each individual. A person’s genes and environment interact in ways that are not yet entirely clear to determine each person’s risk of liver cancer.
It is known that increasing age, male gender, alcohol misuse, chronic hepatitis, a family history of liver (and other cancer), smoking, and liver cirrhosis are associated with an increased risk of developing liver cancer.
Diagnosis of liver cancer is made by doctors based on the person’s symptoms, the signs observed when the person is examined, a number of blood tests and diagnostic imaging such as a CT scan or MRI.
The main problem with liver cancer is that it has usually already spread to other organs before it is detected. Consequently removal of a tumour lump (called resection) is only appropriate in a minority of patients. with secondary tumours in the liver. Transplants are also quite rare in treatment of liver cancers for the same reason.
Chemotherapy is improving but the 5 year survival rate is less than 20% in men and women.
Cirrhosis
Cirrhosis of the liver describes the hardening of the liver from its usual wobbly consistency to a tougher, scarred almost “cooked” state. As time goes by, healthy working liver is damaged and less and less of the liver works properly. Initially the liver is able to compensate by growing bigger and renewing itself. After a point, the liver’s day to day functions decrease and individuals become increasingly unwell and unable to function.
Cirrhosis can be caused by an prolonged or intense contact of liver tissue with various substances including excess alcohol, damage by some drugs, poisons such as arsenic, hepatitis, NASH, inherited diseases such as haemochromatosis, and Wilson’s disease. Sometimes the cause of cirrhosis is not known; the disease is said to be idiopathic.
Alcoholic Liver Disease
When alcohol is broken down by the body the liver does most of the work. There are various stages to the process and some of the compounds that the body changes alcohol into, during the process of converting it to carbon dioxide and water, are toxic. Where small to moderate amounts of alcohol are consumed or where the whole liver functions normally the organ is able to cope and there are few problems. However in many people for reasons that are not yet entirely clear excessive alcohol use, beyond the recommended number of units a week results in damage to various parts of the body but especially the liver in the process of breaking down the alcohol.
The liver reacts initially by accumulating fat (fatty liver) then by accumulating cells of the immune system that react as if the liver were being attacked by a virus or bacteria (hepatitis). If alcohol misuse continues individuals then can go on to develop cirrhosis of the liver and or liver cancer.
Auto-Immune Liver Disease
The body’s immune system is designed to attack bacteria, viruses and other germs that are detected as foreign to the body. One way in which the immune system does this is by producing antibodies to bind those germs and target them for killing by cells that make the immune system. Auto-immune liver disease, also called auto-immune hepatitis is a result of the body making antibodies to parts of liver cells. As with bacteria and viruses, the liver cells are then destroyed by the body’s own immune system. Auto-immune liver disease is a progressive disease; it worsens over time and individuals show more and more signs of illness as they lose more and more of their livers to this illness.
Hepatitis
Hepatitis is an accumulation of the cells and molecules of the immune system into the liver because of infection by a virus. Currently, there are 5 major viral causes of viral hepatitis around the world Hepatitis A, B, C, D, and E.
People are exposed to the viruses in different ways; drinking water contaminated with human faeces, mother to child during pregnancy and the birth process, blood transfusions and blood products as well as sexual contact. The viruses also differ in the detail of how they cause damage to the liver. However the end result is the same; the liver is damaged, unable to work and people become ill.
NASH - Non Alcoholic Steatohepatitis
Alcoholic liver disease differs from NASH because NASH develops in people that drink little or no alcohol. Current thinking is that NASH is one of the most common liver diseases in the developed countries of the Western hemisphere and considered to be influenced by rising obesity, coronary heart disease and diabetes in the same population. Initially NASH does not affect the person’s liver function but may progress to cirrhosis.
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