Role of living liver donation in the United Kingdom

Short abstract

Patients who need a new liver usually face a long wait. Some die before a suitable donor is found. Living liver donation is offered routinely in some countries. Should the United Kingdom follow suit?

Liver transplantation has become an accepted form of treatment for patients with end stage liver disease and those with an unacceptable quality of life because of liver disease. Despite government initiatives to increase donor rates and surgical innovations to maximise the use of existing donor livers, the number of donor organs is insufficient to meet the existing demand. Living liver donation has the potential to help mitigate the deficit and is offered routinely in many countries in North America, Asia, and continental Europe. Living liver donation is not routinely available in the United Kingdom, although a few living transplant operations have been done led by Roger Williams and Nigel Heaton.¹ We believe that living liver donation should be available on the NHS, although it should not be adopted without full public debate and agreement because of the risks to donors.

Current practice

The United Kingdom has no reliable information on requirements for liver transplantation. Although we have data on the number accepted for transplantation,² not everyone who might benefit from transplantation is referred.³ The rate of transplantation is relatively low compared with other European countries (11.6/million population compared with 19.3/million in France and 24.3/million in Spain). However, we do not know the requirement for transplantation because the burden of liver disease in these countries may differ. Donor rates also vary between countries, but the proportion of potential donors who are offered for transplantation is not known. The number of patients dying from liver disease in England is increasing.⁴

Figure 1.

Liver transplant operation

Credit: J L MARTRA/PUBLIPHOTO DIFFUSION/SPL

To be accepted on the transplant list in the United Kingdom, a patient must have a survival probability of greater than 50% five years after transplantation, with a quality of life acceptable to the patient.⁵ These criteria were developed to ensure equity of access and best use of donated livers and to match the numbers of donors and recipients. Patients who would benefit from transplantation but do not fulfil these criteria are not offered transplantation. Thus, not everyone who is put on the transplant list receives a graft (box).

In some cases, the use of the liver can be maximised by splitting it (when the larger right lobe is grafted into an adult and the left lobe into a child or small adult) or the liver can be used after removing a lobe or part of the lobe. Use of livers from non-heart-beating donors and domino transplants can also increase the supply of donors. In domino transplants, a liver is taken from a living donor who has a metabolic defect in the liver such as familial amyloidotic polyneuropathy that results in extrahepatic organ disease; the donor receives a graft (from a cadaveric or a living donor) and the diseased liver is transplanted into an informed recipient whose prognosis is unlikely to be affected by the metabolic defect.

Of the 675 liver transplantations in 2001 in the United Kingdom, 18 were reduced grafts and 62 split liver grafts; no domino transplants were recorded. Survival (based on patients grafted between January 1994 and December 1999) is 80% at one year, 73% at three years, and 64% at five years.

Transplant activity in United Kingdom²

Average No of patients on waiting list 160-170

Average No of transplants/year 720

5 year patient survival 65%

Transplant rate 11.6/million population

Audit of 2001

No of adults registered 647 (139 super urgent)

No of deaths on waiting list 62 (19 super urgent)

No removed from waiting list 47 (25 became too ill)

No of cadaveric liver donors 661

No of transplantations 675

Super urgent patients—not expected to live more than 3 days without grafting

What is living liver donation?

Initially, transplantation was done using whole livers from donors who met the criteria for brain death but whose heart was still beating. Matching was based on blood group and the size of the liver. The graft can be put in the place of the recipient's liver (orthotopic) or elsewhere (heterotopic).

Raia and colleagues introduced living liver donation for children in 1989 because the shortage of donors was increasing the mortality among children on the waiting list.⁶ The left lateral segment (usually about 20% of the donor's liver mass) was taken and implanted into the child (figure). The procedure was then extended to include small adults. By the early 1990s, improvements in the technique had made living liver donation potentially possible for almost all adults.⁷

Figure 2.

Living liver donation may use either the right lobe (for an adult) or the left lobe (for a child)

Adult recipients usually require the right lobe of the donor's liver in order to ensure adequate liver mass. A minimum graft to donor weight ratio of 1% or a graft to recipient standard liver volume ratio of 50% is safe, although a few procedures have been successful at lower ratios. The donor's liver usually regenerates completely in about 12 months, but concerns remain over the risks of the resection and possible complications such as anastomotic strictures or leaks.

Risks to the donor

Current registries suggest that donation of a right lobe for adult to adult transplantation is associated with a 0.5-1% mortality and 40-60% morbidity. The risks of removal of the left lobe are less (mortality about 0.1%).^8-12 The lack of comprehensive registries makes it difficult to assess accurately the risks to the donor, although reports suggest that published mortality data may be underestimates. In comparison, living kidney donors have a mortality risk of about 0.03%, with a 2% risk of major morbidity and 10-20% risk of minor morbidity.¹³ The long term physical and psychological consequences of living organ donation are not established.

Who might benefit?

The potential for living liver donation is limited. In 2002, around one third of liver transplants in Europe and about 7% in North America were from living donors.¹⁴,¹⁵ Many potential recipients cannot receive a liver from a living donor because of medical contraindications in the donor or having no matching potential donors.¹⁶,¹⁷ We believe that living liver donation is indicated for patients who are eligible to receive a liver graft but who have a high probability of death or clinical deterioration that would preclude transplantation before a cadaveric graft became available.

Whether living liver donation should be used for people who do not meet the current criteria for a cadaveric organ remains controversial. Some people believe it is inappropriate to use living liver donation to meet the imbalance between supply and demand while at the same time expanding eligibility criteria to increase demand. However, since the main reason for many of the exclusion criteria is shortage of donor organs, it seems illogical to refuse living liver donation for extended indications if the balance of risks and benefits is reasonable and both donor and recipient understand this balance. We suggest a 25% probability of recipient survival at 5 years with an acceptable quality of life should be the minimal criteria for living donated livers. However, if the graft fails, such recipients should not be eligible to receive a cadaveric organ as they would effectively be bypassing the agreed eligibility criteria.

Is living donation ethical?

It can be argued that well informed donors have an absolute right to determine whether they will give tissue to benefit a recipient and that society (be it government, the courts, or professional bodies) has no right to obstruct an altruistic decision. If so, guidelines need only ensure that the donor receives all the information required to make a well informed decision. However, doctors have an obligation to act in the individual's best interests, which may differ when the donation is to an adult or a child.⁷ Whether the psychological benefit of donation is a sufficient reason to risk a person's life is a matter for debate. An individual's rights can be curtailed for the individual's benefit (such as the enforced wearing of seat belts in cars). The clinical team will have a role in assessing the acceptability of each potential procedure.

A donor may think that the potentially life saving benefits justify the procedure despite the risks. However, these risks should not rise above an acceptable societal ceiling, and the overall balance of risks and benefits between the parties must be favourable. If the recipient's chance of benefit is very slim, the risks to the donor may not be worth taking. The donor must freely and willingly consent to the procedure having been given sufficient knowledge to make an informed decision. Thus, adults who lack the capacity to make such decisions, and probably minors, are not eligible to donate.

The Council of Europe recommendation on liver transplantation from living related donors suggested that living donation should not be done in emergency situations.¹⁸ The time between knowing a patient needs a transplant and the onset of irreversible complications precluding a successful outcome is often short. This gives little time for potential donors to be screened for suitability and adequately educated so that they can make a properly informed decision. Nevertheless, use of living liver donation for fulminant liver failure is widely accepted, and the imminent plight of the patient should not itself rule out the possibility of a live donation.

Current UK legislation

The Human Organ Transplant Act 1989 prohibits commercial arrangements relating to the transplantation of organs from either living persons or cadavers. When a genetic relationship cannot be satisfactorily established, living donation must be approved by the Unrelated Live Transplant Regulatory Authority (ULTRA). The authority will consider close blood relations or anyone with a “close personal relationship” as possible donors. It must be satisfied that there is no commercial arrangement, financial inducement, or coercion and that the donor understands the nature of the procedure and the risks involved.

The 1989 act prohibits donors from being paid for donating but permits payment of expenses connected with donation, such as loss of earnings and travel costs. Donors should also be protected against any financial loss in the future arising from the treatment of injuries caused by donating.¹⁹ Whether the criteria for acceptance for related and non-related donors should be different has been argued.²⁰,²¹ The use of emotionally related donors (which includes family members) for adult-to-adult living liver donations is supported.²²

For cadaveric donation, the graft is considered as a freely given gift and no stipulations are made about the donor; the donation is unconditional and not directed. In contrast, in living liver donation, the organ is given to a specific recipient. We believe that it is unacceptable for family members who are unsuitable donors for their relative to donate to a third party recipient so that the relative gets priority from the donor pool.

Summary points

Living liver donation is available in the United States and parts of Europe but not the United Kingdom

The technique could benefit patients who are likely to die or deteriorate before a cadaveric donor becomes available

The risk of mortality to donors is 40-60% and mortality is 0.5-1%

Procedures must be set up to ensure donors are not coerced and fully understand the risks and benefits

Living liver donation should not be introduced without public debate and approval

Requirements for UK programme

If living liver donation becomes available in the NHS, United Kingdom Transplant (the NHS body charged with overseeing organ transplantation) will need to agree procedures for monitoring the process and, if the technique is used for patients with fulminant hepatic failure, provide a system for rapid response.

Units will need to develop protocols and procedures to ensure that all potential donors are appropriately screened and educated about the risks. Relatives of patients with liver disease will inevitably be under implicit pressure to be assessed for donation, whatever healthcare professionals may say or do. Clinicians must be vigilant in determining whether the donor is really voluntary and in excluding unwilling donors from donation. Independent assessors will be needed to ensure that there is no coercion and safeguard the interests of all participants (including clinical staff).

Standards will need to be agreed and monitored to ensure that the best possible care is given to donors. In addition, a central registry of donors and recipients should, we believe, be set up to follow up donors for life so that long term consequences can be monitored. These steps will require additional resources, but money must not be diverted from initiatives to expand the donor pool and develop alternative treatments for end stage liver disease.

Public support is vital to a living donor programme. A survey of 2000 adults in Great Britain in 2003 showed that nearly three quarters supported living liver donation.²³ Those in favour were more likely to be men, better educated, and younger. Most (74%) supported donors being reimbursed for costs incurred in donation, and 19% agreed that the donor should be paid for donation, although the amount suggested varied widely. About half of respondents thought that a risk of death of 1 in 200 was acceptable for donation to a family member, and 14% thought this was acceptable for donation to a friend.

Conclusions

Making living liver donation available in the NHS will have a small but important effect on the number of people able to receive a graft. It is time for a full public debate on the risks and benefits.