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In 1990, the world's first successful living donor liver transplantation, from a mother to her child, was performed in Brisbane.¹ Over the past three years, living donor liver transplantation has taken off in both the United States and Europe.² In this issue of the Journal, House and colleagues from Western Australia report the first adult-to-adult living donor liver transplantation in Australia.³

This report is worthy of comment because it raises questions as to whether this procedure should be widely adopted in Australia, whether donor safety issues have been adequately addressed, and whether adult-to-adult living donor liver transplantation should be monitored and regulated in Australia.

The upsurge of adult-to-adult living donor liver transplantation in the US and Europe reflects pressures from a mismatch between the demand for liver transplantation and the availability of cadaveric donor organs. In the US, there is a waiting list for liver transplantation of more than 14 000 patients, and a transplantation rate between 4000 and 5000 per year.⁴ The situation in the US is aggravated by an organ allocation system which gives priority to time on the waiting list for non-urgent cases: a patient entering the waiting list "late" is likely to receive a transplant only when there is deterioration to a more urgent category. In this system, deaths of patients while waiting for a transplant have dramatically increased over the past few years (in the US, about 1800 in 1999).⁴ The availability of living donor liver transplantation in an elective setting would presumably reduce or minimise these tragedies by increasing supply to match demand.

This situation is not likely to apply in Australia because, although deaths on the waiting list have risen in the past few years, cases can be prioritised without the need to take time on the waiting list into consideration. Furthermore, in Australia, as in the US, patients with acute liver failure have a national priority listing that potentially minimises death while waiting for a suitable cadaveric donor. Nevertheless, the case report by House et al indicates that some of our liver transplantation units wish to introduce this procedure as an option. Hence, there is a need to address some important issues.

What are the indications for adult-to-adult living donor liver transplantation? In Australia and New Zealand, it has been agreed to offer adult-to-adult living donor liver transplantation only to patients who have already fulfilled the criteria for a cadaveric donation. In the US and Europe, there is also general agreement on this, although some individual units feel that this is too restrictive and perform adult-to-adult living donor liver transplantation on patients who do not fulfil current criteria for liver transplantation, such as patients with large hepatocellular cancers or with acute alcoholic hepatitis. We believe that this is inappropriate; it is nonsensical to argue for the introduction of adult-to-adult living donor liver transplantation to address the supply-demand imbalance and simultaneously expand recipient criteria to increase demand.

How are donors selected? Donor selection clearly requires an agreed formal informed consent process.^5,6 The potential donor should be prepared by a team independent of the team advising and caring for the liver transplant recipient. Input from liaison psychiatrists is crucial. Any hint of coercion should lead to automatic exclusion, with the donor team having the final veto for progressing with adult-to-adult living donor liver transplantation. Potential donors should be selected using criteria that include psychological stability, appropriate vascular and biliary anatomy, age, and absence of underlying systemic or liver disease (eg, donation is contraindicated in an obese subject who is a smoker). A donor should be required to have a major emotional link to the recipient and should not be under any financial indebtedness to the recipient. A donor will usually, but not necessarily, be a close family member. A "cooling off" period after donor consent is also recommended.

Size-matching of donor and recipient is crucial, since "shortchanging" of functioning hepatic mass in either may be fatal. In Australia, this would generally mean that the donation of an adult right hemiliver is required, although in Japan the left liver volume is often sufficient.^7-9

What is the donor morbidity and mortality with adult-to-adult living donor liver transplantation? More than 1000 living donor liver transplantations have been performed worldwide with at least four deaths, although a report of only one has been published.⁴ Significant biliary complications have occurred in up to 5% of donors, and 2%-3% have required more than one surgical procedure. The donor is usually unable to work for 2-3 months, and 70% have persisting symptoms at six-month follow-up.¹⁰

Most living donor liver transplantations have been performed between adults and children, and those between adults include a large number of left liver grafts. This means that the true incidence of morbidity and mortality for right liver grafts remains unresolved. One would expect it to be higher for technical and other reasons related to hepatic mass.

What are the outcomes for the recipient? The survival outcomes for recipients of adult-to-adult living donor liver transplantation are the same as with cadaveric donation, although biliary and vascular complications are increased.⁴

In the case reported by House et al, the patient met the listing criteria for liver transplantation and was on the urgent Australian and New Zealand list for the first available suitable cadaveric donation. The donor was prepared by an independent team in a process that took five days. The outcomes were favourable for both recipient and donor, although the follow-up of the donor is short and the recipient has already had significant biliary complications. However, the use of adult-to-adult living donor liver transplantation for fulminant hepatic failure requires comment. There is an Australasian priority listing for such patients. In the US, such a priority listing has usually obviated the need for adult-to-adult living donor liver transplantation.¹¹ In Australia and New Zealand, waiting list deaths for fulminant hepatic failure are high, in the order of 30%. In Western Australia, the rate is 60%; the reason for this is unclear. Furthermore, in many patients with fulminant hepatic failure, for whom transplantation may be required within 24-72 hours of presentation, a donor consent "cooling off" period may not be possible. In the reported case, five days passed without a cadaveric donor, allowing such fears to be allayed. In many cases, this may not be so.

In the US, it has been estimated that 600 transplantations per year may be possible with the widespread introduction of adult-to-adult living donor liver transplantation.⁴ If this figure is extrapolated to Australia and New Zealand, then between 20 and 30 cases can be expected each year. This amounts to only 1-15 cases in each Australian unit. Is this enough to justify widespread adoption of this procedure? Probably not. A recent commentary suggests that adult-to-adult living donor liver transplantation be restricted to "high case load" institutions,¹² and states:

The rapid proliferation of programmes that perform (liver) transplantation in adults with the use of grafts from living donors (most of those in the United States have performed fewer than 10 procedures each) is alarming for an innovative, nonstandardised operation that places two people, one of whom is healthy, at risk.

It is clear there is a significant learning curve, with higher morbidity in donors and increased complications in recipients at units that have performed fewer than 50 adult-to-adult living donor liver transplantation procedures.⁴ Perhaps a single Australian centre should be established to do these procedures in the elective setting, although this may be logistically difficult to achieve. What is certainly achievable, however, is an agreed Australian and New Zealand protocol for donor and recipient selection, together with a central registry of transplantations performed. The Transplant Society of Australia and New Zealand is currently undertaking this process with the support of all liver transplantation units. The resulting protocol will be placed in the public arena for comment. Similarly, the Australian Safety and Efficacy Registry of New Interventional Procedures (Royal Australasian College of Surgeons) is undertaking a review of the need for adult-to-adult living donor liver transplantation in Australia.

House and colleagues are to be recognised for their courage and ethical and technical skill in performing this procedure in a life-or-death situation. However, only time will tell whether this Pandora's box, containing within it all the issues of adult-to-adult living donor liver transplantation, should have stayed shut.¹³

Geoffrey W McCaughan
A W Morrow Professor of Medicine, and Director
Australian National Liver Transplantation Unit
Royal Prince Alfred Hospital, Sydney, NSW

Stephen V Lynch
Associate Professor of Surgery, and
Director, Queensland Liver Transplantation Unit
Princess Alexandra Hospital, Brisbane, QLD

1. Strong RW, Lynch SV, Ong TN, et al. Successful liver transplantation from a living donor to her son. N Engl J Med 1990; 322: 1505-1507.
2. Renz JF, Busuttil RW. Adult-to-adult living-donor liver transplantation: a critical analysis. Sem Liver Dis 2000; 20: 411-424.
3. House AK, Jeffrey GP, Edyvane KA, et al. Adult-to-adult living donor liver transplantation for fulminant hepatic failure. Med J Aust 2001; 175: 202-204.
4. Proceedings of the 2nd international symposium dedicated to expand the donor pool. Rome. 26 August 2000. Tokyo: CD Toppon Medical Science, 2000.
5. Abecassis M, Adams M, Adams P, et al. Consensus statement on the live organ donor. JAMA 2000; 284: 2919-2926.
6. American Society of Transplant Surgeons' position paper on adult-to-adult living donor liver transplantation. Liver Transpl 2000; 6: 815-817.
7. Yamaoka Y, Morimoto T, Inamoto T, et al. Safety of the donor in living-related liver transplantation — an analysis of 100 parental donors. Transplantation 1995; 59: 224-226.
8. Marcos A. Right lobe living donor transplantation: a review. Liver Transpl 2000; 6: 3-20.
9. Fan S, Lo C, Liu C, et al. Safety of donors in live donor liver transplantation using right lobe grafts. Arch Surg 2000; 135: 336-340.
10. Trotter J, Talamantes M, McClure M, et al. Right hepatic lobe donation for living donor liver transplantation: impact on donor quality of life. Liver Transpl 2001; 7: 485-493.
11. Hymar A, Durand B, Knaak M, et al. Sharing of livers for status I recipients in Region 7 — A good thing. Am J Transpl 2001; 1 Suppl I: 283 (A587).
12. Cronin DC, Millis JM, Siegler M. Transplantation of liver grafts from living donors into adults — too much, too soon. N Engl J Med 2001; 344: 1633-1637.
13. Strong RW. Whither living donor liver transplantation? Liver Transpl Surg 1999; 5: 536-538.

©MJA 2001
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