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Problems associated with liver transplantation

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Bob Hayzen
Former Chairman
ALTA
(Addenbrooke’s
Liver Transplant Association)
Royston
UK
E:rhayzen@bigfoot.com

The first liver transplant to be carried out in Europe was performed by Sir Roy Calne in 1968 at Addenbrooke’s Hospital (Cambridge, UK). During that year, seven such operations were performed. In the year 2000, over 4,000 patients received liver transplants throughout Europe, and by then over 40,000 operations had been performed. Life expectancy has also dramatically increased, due in no small part to improved surgical techniques and the introduction of vital immunosuppressant drugs. Today, it is quite common to hear of patients who have had more than 10 years of normal life following liver transplantation.

Different groups involved
Liver transplantation is a remarkable process that creates a number of very special situations. The relationship between the patient, their family and the hospital team has the potential to develop into a real friendship. This is partly due to the special circumstances associated with transplantation and the fact that, for the patient, hospital visits will probably be necessary for the rest of their lives. In addition, there is the enormous psychological pressure of knowing that, for a transplant recipient to live, almost certainly someone else has to die.

The patient’s perspective
Patients initially meet the hepatologist. After diagnosis and before having a liver transplant, a number of vital hurdles have to be crossed before a patient is placed onto a waiting list. This involves an assessment, which means a hospital stay of one to two weeks, and a series of tests. Donor livers are matched to recipients according to blood group, height, weight and the severity of the patient’s condition. During this time, patients will meet many of the people involved in the transplant process, including transplant surgeons and other doctors, specialist nursing staff, physiotherapists, pharmacists, radiographers and transplant coordinators. For those who are then placed on the list, this is the beginning of what can be a long and anxious waiting period. For those who are not placed on the list, the future is bleak.

Among the patients put on the list, some may be so ill that they have to be admitted to hospital to await their lifesaving operation. Others, supplied with a “bleeper” or carrying a mobile phone, try to lead normal lives, while awaiting the vital call that, hopefully, will be the beginning of a new life for them and their families. For others, the call will not come in time and they will die while still on the waiting list.

This waiting period is described by many patients as the most stressful time of all for themselves and their families.
So much time to think, question their decision and wonder about the risks, and so many things to try to organise: financial and work concerns, children, dependent relatives, visiting arrangements and all the associated time and cost. In addition, someone has to die to provide a new liver. Patients may be given very little notice of their transplant operation, and they are advised to keep a bag ready packed and to have a plan regarding getting to the hospital. When the call does come, it is still not a guarantee that the donor liver will be suitable, as often it has not been seen and examined at that stage. For some, this can mean hopes being raised and then dashed within a matter of hours, and a return to the “waiting game”. During this period of waiting, patients’ minds are often filled with doubts and questions.

Patients need differing amounts of information. Hospital liver transplant teams can usually assess this and respond accordingly. Some, such as the Scottish Liver Transplant Unit, have excellent patient booklets specifically catering for liver transplant patients. In addition, support groups can help with most of these questions. Many patients awaiting a liver transplant will welcome support and a listening ear from someone who has been through the same experience.
These support groups can also provide contacts with community-based organisations and continue to support patients and their families long after their transplant.

In recent years, the internet has become an important source of information for patients, and a number of websites contain information for liver transplant patients.

Transplant unit staff
A special bond develops between the patient and the transplant unit team, and the patient and their family place an enormous amount of trust in them. Inevitably, things will go wrong on occasions, and staff can be deeply affected too, a problem that is often underestimated.

Donors
The increasing effectiveness of transplantation means that many more patients can be considered for such a treatment. However, although there are over 10 million people on the donor register in the UK, there is still a serious shortage of donors. For some people this can mean waiting, sometimes for many months, and of course for too many it means they will die before a suitable organ becomes available.

In recent years, organisations such as UK Transplant and the British Organ Donor Society have run campaigns to increase awareness among the general public. Some local authorities have sent out material inviting people to sign the organ donor register. Discussions are being held between various European governments, and one consideration is to encourage nations to accept a system of “opting out” when it comes to organ donation, with some European countries having already implemented this system. This would mean that, unless a person specifically signs an “opt-out” clause, their organs could be used for transplantation in the event of their death.

The transplant operation
When the call does come, further blood tests and X-rays will be performed when the patient arrives at the hospital. After the donor liver has been confirmed as suitable, the operation can take place. The length of the operation varies with each person but tends to take between 6 and 10 hours on average. If the patient has had previous abdominal surgery, it may take longer.

Immediately after the transplant operation, patients are taken to an intensive care unit, or high-dependency unit, where they are closely monitored and have a designated nurse to specifically care for them. They stay in the unit for approximately 1 to 3 days, depending on their condition.

Pain control is often achieved by using a regulated pump that enables the patient to inject small, carefully controlled doses of analgesic. Morphine still tends to be the drug of choice. Many patients experience hallucinations and nightmares, and some liver units are carrying out research into this particular problem.

Patients have a large wound in the shape of an inverted T and two tubes, which are usually removed after 2–3 days. They are also attached via necklines that provide nutrition, fluids and drugs. A nasogastric tube is used to drain stomach contents, in addition to a catheter. If progress is satisfactory, these tubes can be removed after a few days.

Once the patient’s condition is stable and they can breathe unaided, they are usually transferred to the transplant ward, where the average length of stay is three weeks. However, this can vary enormously, depending on a number of factors.

Problems following transplant

Transplant rejection
A number of problems can follow liver transplantation, the most serious of which being rejection. Despite the use of immunosuppressant drugs (such as tacrolimus, sirolimus, azothioprine and cyclosporine), it is estimated that up to 60% of patients develop some degree of acute rejection in the first few weeks following a transplant. This is often treated with a short course of high-dose steroids.

The symptoms of rejection vary. Some people feel feverish and lethargic, others become jaundiced or suffer from severe itching, while others feel no symptoms at all although changes in their liver function are detected on their blood tests. The suspected diagnosis of acute liver rejection is usually confirmed by a liver biopsy.

Dosage levels are critical, and regular blood tests are performed to check blood levels. The pharmacist’s advice is vital to ensure that patients fully understand the importance of taking these drugs. Patients are advised not to take these drugs with grapefruit juice or to eat grapefruit, as it can significantly affect the blood levels of the immunosuppressant drugs. Drug interactions are also an important factor that patients need to be aware of.

Finally, a small proportion of patients experience chronic rejection, which occurs later, is much more difficult to treat and can lead to the need for a second transplant.

Potential infections following transplantation
As a result of the antirejection therapy and the suppression of the immune system, patients are more likely to develop infections, particularly during the first 3 months. The more common infections include viral infections, cytomegalovirus CMV, herpes simplex, herpes zoster, varicella zoster and candida.

Diet
The dietician takes an active interest in the transplant patient. Some people lose a large amount of weight before their operation. Thus, it is important that during the first 3 months after a transplant patients avoid eating food that may contain listeria.

Drinking alcohol is not advised in the first few months following a transplant, and any subsequent consumption should be carefully discussed with a hepatologist. Liver disease decreases ability to absorb vitamin D, and the diet needs to take this into account.

Thanking the donor’s family
Many people wish to find out at least a little about their donor. However, as a promise is made to the donor’s family that confidentiality will be maintained, minimal information is available at first. If a recipient wishes, they will be told their donor’s age and the cause of their death. Many families of donors are grateful to receive a letter from the recipient or a member of their family. The transplant coordinator is usually the most appropriate person to answer questions of this kind and regarding any letters to the donor’s family. The decision to write to a donor’s family is one of personal choice. Advice regarding the content and style of such letters may be obtained from the transplant coordinator.

Support groups
Patient support groups have developed in many liver transplant units. They have been set up in response to an overwhelming need for help and advice from people who have been through transplantation themselves. Working closely with hospital staff, they are able to provide support before, during and after the transplant. Many of the groups have telephone helplines, websites, newsletters and information leaflets. Some provide volunteers who visit the wards and also attend the outpatient clinics to support and advise patients.

Conclusion
Liver transplantation is a dramatic event involving many people and leading to many serious challenges. It literally provides a dying patient with a second chance. In the past 30 years, diagnosis, assessment, technique and medication have all improved significantly. However, waiting lists have grown, and the limited number of available donor organs is a cause for serious concern.

In an attempt to resolve this problem, various solutions have been envisioned. Live liver donation is practised in some countries, particularly the USA. However, there are a number of serious problems associated with this practice, not least the huge psychological challenge of having two family members undergoing serious life-threatening surgery. Research into new immunosuppressant drugs continues, and in the long term there is the possibility for stem cell research to provide an answer.

Resources
Addenbrooke’s Hospital Transplant Unit
W:www.cambridge-transplant.org.uk
British Liver Trust
W:www.britishlivertrust.org.uk
Children’s Liver Disease Foundation
W:www.childliverdisease.org
Primary Sclerosing Cholangitis Support Group
W:www.psc-support.demon.co.uk
Primary Biliary Cirrhosis Foundation
W:www.pbcfoundation.org.uk
Hepatitis C Information Page
W:www.hepc.org.uk
Haemochromatosis Society
W:www.ghsoc.org
British Organ Donor Society (BODY)
W:users.argonet.co.uk/body
UK Transplant (NHS)
W:www.uktransplant.org.uk



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