LIVER TRANSPLANT SERVICES
DONOR ORGAN USE - PROTOCOLS AND GUIDELINES
FOR ADULTS UNDERGOING CADAVERIC LIVER TRANSPLANTATION
Published: November 1999
Revised: March 2000
Revised: April 2001
Reviewed: May 2002
Revised: August 2003
Reviewed: May 2004
Revised: January 2005
- Introduction
- The Need for Transplantation
- Assessment
- Patient Registration
- Allocation of Donor Livers
- Conclusion
There remains a gap between the number of patients suitable for liver transplantation and the number of donated human livers so that decisions on selection of patients for liver transplantation have to be made on criteria other than just medical need. Following the death of a young woman with liver failure, a colloquium was set up in 1999 to discuss guidelines for selection of patients for transplantation and attended by transplant clinicians, patient representatives, health care professionals and medical ethicists. This paper combines the results of that colloquium with other extant guidance on the allocation of donor livers.
It was agreed that livers donated for transplantation should be considered a national resource and therefore guidelines for their use needed to be agreed publicly and followed nationally. Patients should be considered for transplantation if they had an anticipated length of life (in the absence of transplantation) of less than one year or an unacceptable quality of life. Patients should be accepted for transplantation only if they had an estimated probability of being alive 5 years after transplantation of at least 50% with a quality of life acceptable to the patient. Should the patient’s condition deteriorate whilst waiting for a liver so that these criteria are no longer met, the patient should be removed from the list. Other medical and social factors (such as alcohol or drug mis-use, age or antisocial life style) are not directly relevant other than whether they affected the above criteria; implementation of these guidelines should be left to those responsible for the care of the patient. As with any guidelines, there needs to be continued re-assessment and modification.
The full guidelines produced from the colloquium, and accepted as the basis for assessing patients for liver transplantation by the Directors of Liver Transplant Units in the UK and Republic of Ireland, were published in the Lancet (Guidelines for selection of patients for Liver Transplant in an era of Donor Organ shortage: 199 vol 354 (910): 1636-1639).
The principles through which donor livers will be allocated are discussed and agreed through the UK Transplant Advisory Group network. Copies of the protocol (which is updated from time to time) are available at UK Transplant.
It should be noted that this document considers transplantation into adult patients of whole or split deceased donor livers and for routine and super-urgent listed patients but not transplants of livers from living donors. The same principles will be applied to transplantation into paediatric patients (under 17 years), but see Section 2.2.
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1.1 The transplant specialty within the NHS is relatively new: liver transplants have a shorter history than the specialty as a whole. All forms of transplantation do, however, carry certain common features: with the exception of kidney failure for which dialysis is an option, it is the only treatment available in the case of major vital organ failure; it is also entirely dependent upon a source of donor organs which is outside the control of clinicians or commercial suppliers. Developments in cell growth techniques and xenografting give rise to hope but for the future. The following guidelines are intended to apply to the use of cadaveric donated livers (whole or split) but not to livers from living donors. The method of allocation of donor livers is subject to separate guidelines.
1.2 As with most emerging specialities, the number of patients who could benefit from the treatment has changed over the years and waiting lists have risen in recent years. Equally, research and development has ensured that outcomes in terms of survival have increased to a remarkable degree.
1.3 The supply of donor organs is a limiting factor and one which has resulted in the development of a national organ sharing scheme to ensure equality of access to treatment throughout the NHS. The rapid increase in the number of patients with disorders which may benefit from transplantation and ‘diagnosed’ as suitable for transplantation has not been matched by the availability of donor organs. In recent years research and development by transplant units extended the margins and has increased the proportion of available organs, which are useable. Splitting livers has, in some cases, also been possible so as to increase the organ transplants available; similarly, living lobe donation has also provided a transplant for a few patients. Non-heartbeating donors may also provide suitable grafts.
1.4 A high level of co-operation is necessary UK-wide between Units and exists to ensure the retrieval of all possible available organs. The surgical technique for transplanting organs and associated skills have been developed in order to use a higher proportion of retrieved organs. Also, their rapid and efficient use, with sharing based on equitable protocols, which are agreed by the profession nationwide, is needed.
1.5 Associated with the increased success of transplants is an increased length of survival for transplant patients, coupled with groups of higher risk patients being treated. Such protocols must balance the often-competing issues of equity of access for all with overall utility(or benefit in outcome). Higher levels of skills are now required in assessing patients prior to their being placed on the waiting list, and in their post transplant maintenance and follow-up.
1.6 The Government has invested additional resources to increase the donor pool and in the year 2003/4, there was a 4% increase in donor rates. The number of patients listed for transplantation, and grafted, is remaining stable but this observation does not indicate that the overall need for liver transplantation is stable. The assessment process remains critical and as more patients at higher risk are being treated, the follow-up protocols required for individual patients may be more complex.
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2 THE NEED FOR TRANSPLANTATION
Conditions preliminary to assessment for Transplant
2.1 Referral to a Transplant Unit - Most patients with liver disease are not managed in transplant units. Patients referred for assessment for liver transplant will include those with the following broad categories of conditions.
| PRIMARY RECIPIENT DISEASE | |
|---|---|
Cirrhosis: |
Secondary sclerosing cholangitis |
|
Alpha -1-antitrypsin deficiency |
| Budd-Chiari syndrome | |
| Wilson's disease | |
| Biliary atresia | |
| Non-alcoholic fatty liver disease | Other congenital biliary abnormalities |
| Chronic active hepatitis (autoimmune) | Acute/subacute fulminant hepatic failure (FHF) |
| Chronic viral hepatitis B | Primary hepatocellular CA in cirrhotic liver |
| Chronic viral hepatitis C | Primary hepatic malignancy |
| Congenital hepatic fibrosis | Inborn errors of metabolism not in CLF group |
| Primary sclerosing cholangitis | |
2.2 The broad indications for transplantation are usually accepted to be either an unacceptable quality of life (because of liver disease) or anticipated length of life is less than one year (because of liver disease). For many conditions there are clinical guidelines and algorithms to help the clinician decide whether a patient meets either of these criteria: patients meeting either of these should be offered a transplant only if the clinician feels that they have a greater than 50% probability of survival at 5 years after transplantation with a quality of life that is acceptable to the patient. Thus outcome criteria become an integral factor in the selection process. It should be noted that these criteria are not based on validated rationale and further work is being done to refine them; additionally, the criteria will need to be modified according to the balance between donor livers and recipients. It should also be noted that different criteria may be appropriate for children. The British Society of Gastroenterology has published guidelines on the indications for referral and assessment in adult liver transplantation: a clinical guide (Devlin J, O'Grady J, Gut 1999:45;suppl 6; vi1-vi22).
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3.1 Assessment is carried out by the transplant multi-disciplinary team. It is usually desirable for the patient's family to be involved in the assessment process. These initial assessment procedures often follow outpatient review and consultation and are undertaken over several days; patients remaining on the waiting list will be re-assessed at intervals during their wait for a donor organ.
3.2 The decision whether or not to register a patient on the transplant waiting list will be made after discussion with the patient and other relevant healthcare professionals. The patient’s family and partner usually will be involved as patients find that helpful and the family’s support is likely to improve the eventual outcome. Other factors which will need to be considered will include the reason which gave rise to the primary cause of liver failure (for example, alcohol-induced liver diseases); a history of illegal drug use or of self-inflicted; medical or psychiatric conditions; and the patient’s age. These are discussed briefly below.
3.2.1 Alcohol-induced liver disease A history of excess alcohol is relevant in regard to potential or actual significant damage to cardiovascular and neurological tissue, or to the risk that patients might revert to alcohol abuse or might not comply with medication or follow up schedules and thus damage the new liver. A multi-disciplinary approach is required to select patients who are likely to comply with follow-up and not return to a damaging pattern of alcohol consumption after transplantation and may include psychological/psychiatric assessment. Appropriate follow-up strategies may be needed.
3.2.2 Illegal drug use Is not a contraindication to transplant if the patient will comply with the required schedules. However, continued intravenous drug use is considered a contra-indication owing to the possible risk of infection in an immune-suppressed patient.
3.2.3 Age In itself is not a contra-indication, although the survival rate after transplant of the over 65s is significantly worse than that of younger patients.
3.2.4 Self-inflicted conditions Such as resulting from an overdose of paracetamol would only be contra-indicated if there were good reason to believe that the patient would, despite appropriate support, return to a behavioural pattern that would lead to liver failure or result in a quality of life unacceptable to the patient. The views of the family doctor and other support agencies and the family may have to be taken into account.
3.2.5 Medical and psychiatric conditions
3.2.5.1 Concurrent extra-hepatic co-morbid medical or psychiatric conditions are relevant if they will affect the patient’s quality of life or prospect for survival post transplant. Where uncertainty remains,evaluation should be considered in discussion with other transplant units and, where appropriate, the Managing & Transplant Director of UK Transplant/Chairman of UK Transplant Liver Advisory Group.
3.2.5.2 Patients in whom early graft damage from recurrent disease can be anticipated should only be transplanted as part of an agreed protocol of treatment. There are well-developed protocols now to prevent or treat the effects of recurrent HCV and HBV infections but problems remain with hepatic malignancy.
3.2.5.3 With the advent of effective treatment, those co-infected with the HIV may be suitable candidates for transplantation.
3.2.6 Regrafts Will need special consideration dependent on the circumstances which gave rise to the need for regraft, as results after early re-graft are poor and only limited benefit may be achieved. However, the principles that apply to primary grafts should also apply to re-grafts.
3.2.7 Malignancy Where potential liver allograft recipients have suffered from previous extrahepatic malignancy, the decision to proceed for liver transplantation should depend, in part, on the probability of malignancy recurring following liver transplantation. Some immunosuppressive agents may encourage the growth of malignancy. Patients should be considered in the light of section 2.2. With patients with primary hepatic malignancy, there are agreed criteria which predict a high probability of tumour persistence after transplantation: these include number of lesions, size of lesions, portal vein involvement and spread outside the liver capsule. Most data suggest that more than 3 liver tumours with a maximum diameter of 5 cm indicates that hapatocellular cancer is likely to persist following liver transplantation and the criteria in section 2.2. will not be met. However. These criteria are under regular review and a slight expansion, using the UCSF criteria, may be appropriate. The role of interventions that shrink the tumour (such as chemoembolisation) remains uncertain and extension of the conventional indications should be done in the context of agreed studies. In general, those known to have cholangiocarcinoma are not appropriate candidates for transplantation.
3.3 It also has to be recognised that patients awaiting a liver transplant are, by definition, ill and their condition may deteriorate to the extent that the probability of a 5-year survival may fall below 50%. In these circumstances, the patient will be removed from the waiting list but only after full discussion with them. Such patients - although in greatest need - are at greatest risk of not benefiting after transplantation.
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4.1 Patients placed on the transplant waiting list following assessment must be registered on the National Transplant Database and logged into the local hospital patient administration system. The National Transplant Database is managed by UK Transplant which holds detailed information about each patient awaiting any organ transplant in order that they may have as up to date as possible a picture, at any one time, of the state of waiting list requirements. Patients who have not been registered should not be offered an organ.
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5.1 The principles through which donor livers will be allocated are discussed and agreed through the UKT Users' Advisory Group network.
You may access the Donor Organ Sharing Scheme by clicking here.
5.2 These guidelines do not specify which patient to select when a liver suitable for more than one patient becomes available. There may be many factors such as the quality and size of the liver and blood group, the health of the patient and pressures on beds and staff, which will influence the choice of recipient. In general however patients with equal criteria will be selected on the basis of length of time they have waited. Similarly, these guidelines do not help the clinician decide between two recipients or to decide whether a liver should be transplanted into a patient who is dying from end-stage liver disease or into a patient with an intolerable quality of life (for example, because of intractable itching). However, when equal outcome is anticipated then the sicker patient would normally be selected. A patient’s contribution to society or ability to pay must never be factors in consideration. For these and other reasons, the development of these guidelines will be assumed by the United Kingdom Transplant Liver Advisory Group.
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The imbalance between donor supply and need for liver transplantation is likely to grow further. Inevitably clinicians will face complex issues and should be encouraged to discuss them openly in a mutli disciplinary team environment which encompasses the views and needs of patients who should have every opportunity to express their concerns.
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