Liver transplantation

Liver transplantation was first undertaken in humans in 1983 by Starzl and later Sir Roy Calne started the first UK liver transplant programme in the UK in 1985. At first, outcomes were very poor, with few patients surviving the first year. However, advances in surgical expertise, in selection of donors and recipients, in the medical and anaesthetic management, newer agents to combat infection and to prevent and to treat rejection have meant that outcomes are now hugely better, with many patients returning to a length and quality of life that approaches normal.

Liver transplantation is a major procedure that has enormous implications for the patient and their family. Life after transplant is usually very good but it is not normal. Thus, transplantation is not to be considered as a cure but more as a swap, where the benefits and risks of the procedure must be balanced against the risks and benefits of no-transplant.

Indications for transplant
In general, patients are offered transplantation to improve either length or quality life.

Length of life:
There are many conditions that affect the liver and result in liver failure, when the liver fails to sustain a normal life and may lead to premature death. Liver failure is usually divided into two categories: acute and chronic.
    Acute liver failure: in acute liver failure, some one with a previously normal liver develops liver failure and, in some cases, this rapidly leads to coma and then is associated with a high risk of death, unless transplantation is undertaken.
    Chronic liver failure: this results from a large number of causes that can lead to cirrhosis: causes include excess alcohol, viruses (such as Hepatitis B and C), autoimmune conditions (such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis) and metabolic diseases. The liver function progressively deteriorates and this results in symptoms such as jaundice, confusion, fluid in the abdomen (ascites) and liver cancer.
    
Quality of life
Sometimes, although the liver is working reasonably well, the liver disease is associated with severe symptoms, such as intense itching that cannot be controlled by medical or other surgical means. This can be an indication for transplantation.

Assessment for transplantation
This section will focus on assessment of the patient with chronic liver disease.
Most patients with chronic liver disease are followed in specialist liver clinics and the doctors involved will consider whether the time is right for assessment for liver transplantation. When the time to consider transplantation approaches and if the patient is keen to consider this option, a period of assessment will arranged: depending on the situation, this can be done either as an in-patient or an out-patient in a designated transplant unit.

Transplant Units
There are seven liver transplant units in the UK, located in
    Addenbrookes Hospital Cambridge
    Freeman Hospital, Newcastle-upon-Tyne
    St James’s University Hospital, Leeds
    King’s College Hospital, London
    Queen Elizabeth Hospital, Birmingham
    Royal Free Hospital, London
    Royal Infirmary, Edinburgh

These Units are designated by the National Commissioning Group which represents the Health Departments of all four UK nations.

The purpose of the assessment is to answer the following questions:
•    Is now the time for consideration of a transplant
•    Are there other treatments that can make the patient better or ‘buy time’
•    Can a transplant be done safely
•    Are there issues that need to be resolved before a transplant can be done safely
•    Does the patient want a transplant
 
Before these questions can be answered, the clinical team have to have full information not only about the condition of the liver but also the heart, lungs circulation and so on. The patient will need to have time to be given all the information and understand both the benefits and risks of the procedure and what it will mean not only for the patient but their family. It is a key part of the assessment that all information is given and there should, where possible, be enough time to take in all the issues.

What is done at the assessment
Centres will vary but the process involves a full educational programme for the patient so that he/she knows what is involved for them and their family. Most centres will arrange for the possible transplant patient to meet those who have had the procedure. The patient will also meet the team which will include physicians and surgeons, anaesthetists, pharmacists, coordinators, physiotherapists, dieticians, nurses amongst others.

There will be many investigations undertaken, the nature will depend on the individual.

At the end of the assessment period, the patient and the clinical team will reach one of the following conclusions:
•    The person is placed on the transplant list
•    Transplantation is considered too early and the decision deferred
•    The person wishes to have more time to reach a decision
•    The transplant cannot proceed for technical or other reasons
•    The transplant cannot take place because it is too high risk
•    The patient does not wish to have a transplant

Selection
This is when the patient is placed on the waiting list.

There is a shortage of livers for transplantation in the UK (as in all countries) and therefore not everyone who could benefit from a transplant can get one. Therefore there has to be rationing: this has to be done on a basis that is transparent and fair and applies to all patients across the UK.

The agency responsible for overseeing this is the Organ Donation and Transplantation Directorate of NHS Blood and Transplant. Guidelines have been drawn up so that there is transparency, equity and equality. The criteria for selection have been published and are available from NHSBT. These guidelines cover not only the medical indications but also social factors, such as dealing with those who have damaged their liver from alcohol. These were drawn up after discussion with health care professionals, those expert in ethics as well as patients, their families and patient support groups. These guidelines are being monitored and revised as needed.

When a person is placed on the transplant list, the coordinators will agree the process of letting you know when a suitable graft is available and agree how you will get to hospital safely.

The National Waiting list
There is a national waiting list which is held by NHSBT. There are two lists:
Super-urgent list: this list is for those patients who have acute liver failure. Patients on this list will normally be expected to live only a few days before dying from the liver failure.
Urgent list: this list includes every one who is listed for a transplant and is not in the super-urgent class.

Suspended: sometimes patients are suspended from the waiting list, because of, for example, an infection or a wish to have a holiday.

While on the waiting list
This is a very difficult time for the patient and their family: there is a constant tension waiting for a call. It is important to use the time to maintain and even improve (where possible) fitness for surgery. It is important that the patient keeps in contact with the Recipient Transplant Coordinator who should be informed when there is any change in the clinical condition.

Donation
In the UK, there are several types of donor:
Living donor: in living donation, a healthy individual (usually a close family member) will donate part of their liver to the recipient. The operation on the donor carries a very small risk but the consequences can be very severe. For this reason, all potential living donors are very carefully evaluated before donation can proceed and the Government (through the Human Tissue Authority) plays an important role in ensuring that the donor is fully informed as to the risks and benefits and there is no coercion. Few centres in the UK undertake this at present.
Deceased donor: this is a patient who is brain dead (perhaps as a result of a massive stroke or head trauma in a car collision) but the heart is still beating. When a potential donor is identified, the clinical team will approach the relatives to find out if the person had indicated they would like to be a donor. If so, a donor transplant coordinator will approach the family, take a full history and request blood tests to make sure that the donation will not give excess risk to the recipient. An independent team will conduct two sets of tests to make sure that the donor is truly brain dead before the surgical team will come to retrieve the organs for transplantation.
Non-heart beating donor: in some cases, the team will wait until the heart stops beating and then the surgical team will remove the organs for transplantation.

The liver that is removed may be:
A whole liver
A split liver: this is where the liver is divided into two halves: usually the bigger portion is used for a larger adult and the smaller portion for a child or a small adult. All livers are considered for splitting.
A cut-down liver: where the liver is too big, part of the liver may be removed by the surgeons and the rest transplanted.

Many people who have had a transplant take time to come to terms with the fact that the liver comes from a dead person. It is important to remember that the donor did not die to provide a liver, rather out of one person’s and one family’s tragedy has come new life not only for the recipient or recipients of the liver but may be also the kidneys, the pancreas, the heart, the lungs, the eyes and the intestine. This thought is often a great consolation for the family.

Allocation
Allocation describes the process where a recipient is selected for a liver that has been donated.
There are several factors that will determine how the recipient is selected. The most important factors are blood group and size match between donor and recipient. The next most important factor is whether there is a recipient on the super-urgent list. Such a patient gets top priority: there is a national waiting list that covers the entire UK.

If there is no suitable recipient on the super-urgent list, then the liver will be allocated to the transplant centre in the zone of the donor. The size of the zone will depend on the number of patients on the waiting list for each centre and is carefully adjusted to ensure that all patients have an equal chance of getting a liver, irrespective of which centre they are listed.

The surgeon will decide, often after consultation with colleagues, who is the best candidate to get the liver. Many factors will come into play in reaching the selection and will include the health of the recipients and the quality of the liver. Some livers (also called extended criteria livers) may not work quickly so are more suitable for those who are less ill.

The call
When a liver graft is available and the recipient selected, the patient is contacted and arrangements made for admission. There is usually no great urgency; patients are often contacted in the afternoon and the procedure scheduled for the following morning. On admission, the patient is examined and blood tests taken. Sometimes the operation may not proceed: either the recipient is not well enough (such as a chest infection) or the donor is not suitable (for example, the liver is very fatty and will not function or the donor may have a cancer that would be transmitted with the liver. While it is always a huge disappointment for all concerned, it is far better to postpone surgery for another day rather than proceed with an operation doomed to failure.

The operation
This is a complex procedure where the old liver is removed and the new one plumbed in. The procedure is often very time consuming and make take 8 or 12 hours; the length of time of the procedure is no guide to the success. Blood loss, which used to be a major problem, is much less of an issue with many operations being done without any blood transfusion.

The new liver is usually put in the same place as the old liver (orthotopic) but very occasionally the native liver is left alone and the new liver placed elsewhere in the abdomen (heterotopic). Sometimes, only part of the native liver is removed and a split liver put alongside the old liver (auxiliary orthotopic)

Post-operation
After the operation, the patient is returned to the Intensive Care Unit. Depending on many factors, the patient will remain on the ventilator for a few hours or days and be discharged after several days to the ward and then home. The length of time varies greatly but many patients are home within 2 weeks of surgery.

Recovery is gradual and, for most people, it takes 9 to 12 months to get full recovery.

Rejection and Immunosuppression
To prevent the liver being rejected, the recipient must take immunosuppression. For the great majority, this is life long. There are many different agents available, all with their own activity and side-effects. Usually, for the first few weeks, there are a lot of medicines to take, but as the liver ‘beds in’, these are reduced but most recipients will need life long monitoring to ensure that they are getting the minimum amount to present rejection.

Rejection of the liver is divided into two types: acute and chronic; both forms can occur at any stage although acute rejection, seen in less than half, often occurs within the first three months and chronic mainly within the first year. Rejection can be diagnosed only on liver biopsy and usually responds well to changes in immunosuppression. The liver is less susceptible to rejection than the kidney or heart.

Survival after transplant
There is the potential for all sorts of complications after transplant. Overall, there is a greater than 90% chance that the recipient will be alive and well after one year. Survival after that is usually very good, both in terms of length of life and quality of life. Initially, doctors focussed on one year survival but now we are seeing many people 20 years out from their transplant and still doing well. Survival of the graft depends on many factors.

Sometimes the original disease can recur in the graft and this may affect the long-term function of the graft. People who have had a liver transplant are also at slightly greater risk of some conditions, including an increased risk of heart disease and stroke as well as some cancers (particularly of the skin). These can often be prevented or treated successfully. Patients should lead a normal healthy life, avoiding smoking and eating a sensible, balanced diet. Return to work is to be encouraged in most cases (not, for example, for boxers or sword swallowers!) and many female recipients are able to have a successful pregnancy. These and other medical matters should discussed with the clinicians responsible for the care.

The whole point of the transplant is to return, as far as possible, to a normal life: certainly, there will be some restrictions, such as the need to take life-long medication and attend follow-up but, for most, this is an acceptable price to pay for a longer symptom free life.