LIVE – DONOR LIVER TRANSPLANTATION

Background

Live-donor liver transplants have been undertaken since 1988. The method was not successful until Russell Strong in Brisbane (NEJM 1990 322:1505-1507) undertook his 1989 case of a 17-month old Japanese boy who had a graft from his 29-year old mother – both of whom are long-term survivors. There have now been approximately 1500 performed worldwide, by far and away the majority of which have been adult-to-child (approximately 1250). Adult-to-child transplants involve taking the left lateral segment (segments 2 and 3) or the left lobe (segments 2,3 and 4) from an adult, procedures which have proven to be relatively safe when applied to liver resection. It is not possible to know for certain the number of fatalities amongst these 1250 donors but the reported number at the 1999 International Liver Transplantation Society Meeting (Pittsburgh) was 3, giving a donor mortality rate of 0.24%. This is approximately twice that of the accepted donor mortality rate for live kidney donors of about 0.1%. Whilst live-donor liver transplants for paediatric recipients have been done in reasonable numbers with what has been regarded as an acceptable donor mortality, it is a procedure that has been confined to relatively few centers worldwide. With the more frequent use of split liver transplants (using one cadaveric liver for one adult and one paediatric recipient) the need to use live donors for paediatric patients is seen to be diminishing. There has, however, been a surge of interest in adult-to-adult live donor liver transplants because of the increasing size of waiting lists, the concomitant increase in waiting list deaths and the apparent success of the procedure in Japan where cadaveric organs are scarce and there are no alternatives. Adult-to-adult transplants potentially increase the stakes because; (i) the transplanted portion is necessarily larger, representing a more major donor procedure, and (ii) the transplanted portion may be marginal in terms of size for the recipient, resulting in increased morbidity and potentially mortality. It is these issues that demand discussion prior to the implementation of such a procedure.

The risk to the donor

There have been approximately 250 adult-to-adult live donor liver transplants performed worldwide. Most of these, approximately 180, have been done in Japan where no donor mortality has been observed. There has been one reported right lobe donor death in the U.S. that resulted from torsion of the liver remnant on the hepatic vein(s) resulting in acute outflow obstruction and subsequent liver failure. This would put the risk at 0.4%, 4 times that of live kidney donation. The prospective donor surgeon for our unit would be Dr John McCall who has personally performed more than 100 elective liver resections without a perioperative death in non-cirrhotic patients, and without encountering torsion to the remnant liver. The chief complications described in donors include bile leak, prolonged jaundice, pulmonary embolism, pneumothorax, bleeding peptic ulcer, and other more minor morbidity. Nevertheless, the mean hospital stay for the donors is about 8 days.

The risk to the recipient

The overall one-year survival rate of adults receiving live-donor liver transplants is 78% in Kyoto, Japan there being a significant difference in outcome for elective (80%) versus acute (64%) cases. All other centers have performed fewer transplants but in general with better outcomes. In Hong Kong, there have been 23 right lobe transplants and 21 patients (91%) were alive at the time of the ILTS meeting in August 1999, although this does not represent one-year survival. In Richmond, Virginia there have been 40 right lobe transplants. Of these 40 recipients, 35 (88%) were alive at the time of the report, but again the follow-up is relatively short. The 5 deaths were all in the first 15 cases and were in patients with very advanced chronic liver disease unable to leave the hospital (UNOS status 2A). Subsequently, such patients have been avoided. The one-year survival rate at Shinshu University in Matsumoto, Japan is 85%. These results are probably not statistically different from those achieved in patients receiving whole organ transplants or split liver transplants. Many of the more excellent centers around the world achieve patient survival figures of 90% at one year with whole liver allografts, and the Australian and New Zealand Liver Transplant Registry indicates a current one-year survival rate of 90%.

The other aspect of recipient risk is morbidity. There is little doubt that this is dramatically increased in recipients of live-donor grafts. The key differences are prolonged post-transplant cholestasis, biliary leaks and concomitant sepsis. These combine to produce an average length of stay that is several fold higher than for recipients of whole organs. The cholestasis seems to be related to the size of the transplanted portion of liver and to the degree of portal hypertension. Where the portion of liver is well above 1% of body weight or >50% of the predicted liver volume, and portal hypertension is absent or minimal, the incidence and duration of cholestasis seems reduced. The increased incidence of biliary leaks seems inevitable because most right lobes require Roux-en-Y drainage of >1 bile duct. The contribution of insufficient arterial supply to the transected bile duct ends is unknown but is a theoretical possibility given current concepts of microvascular anatomy. While the majority of leaks can be dealt with either surgically or by stenting, the accompanying sepsis is problematic and potentially lethal.

Issues of consent

Informed consent is clearly crucial to laying out the option of adult-to-adult (or for that matter adult-to-child) live donor liver transplantation to either a potential donor or a patient awaiting a liver transplant. Most centers involved in providing this option are very careful in relation to donor consent. Most would regard perceived solicitation or coercion as contraindications to allowing donation to proceed. Once a prospective donor has identified himself or herself, there is usually a two or three part process involving a medical and psychiatric review, the granting of consent, a "cooling off" period where consent can be withdrawn, the final portion of evaluation (including radiology) and it is not until this point that live donation proceeds. While this is clearly important it is not qualitatively different to the consent process used in Auckland Hospital for live kidney donation. Urgent cases (for recipients with fulminant hepatic failure) require compression of this consent process into the time available (36-48 hrs) and the possibility of coercion is seen as a potential issue in such a scenario. Recipient consent is less problematic in that such patients have already been informed about the usual risks and benefits of liver transplantation. Apart from those patients with fulminant hepatic failure, all that is required is a clear identification of the increased risk posed by receiving a portion of a liver rather than a whole organ. Such a discussion would also need to occur if the patient was offered a split or cut-down liver, as is the case for most children.

The issue of innovative procedures

Whilst live-donor liver transplantation is not novel, it is new to New Zealand. As a group we are therefore committed to a consultative process to ensure that ethical considerations are properly addressed. The 1996 National Standard for Ethics Committees included in the job description of regional ethics committees that they "ensure that the ethical aspects of innovative procedures, both therapeutic and diagnostic, are adequately considered". The purpose of lodging this discussion page on our website is to allow feedback and to thereby provide both public and peer review of the proposed introduction of this procedure. Such feedback could help shape the final proposal and any submission to the regional or national ethics committees that may care to review such a proposal. In general we would like to proceed with the following:

1. Lodge this discussion page on our website and encourage feedback
2. Allude to this discussion page in a letter to the New Zealand Medical Journal
3. Formulate a plan regarding the selection of patients for whom living donation would offer an advantage*
4. Submit the plan to regional/national ethics committees
5. Undertake an initial series of live donor transplants
6. Publish the results of this series in a letter to the New Zealand Medical Journal and on our website

If the endeavor turned out to be clearly successful, we may wish to broaden its application. If, on the other hand, this were disadvantageous for either donors or recipients then we would desist and state our reasons for so doing.

* For discussion purposes, patients who currently have a limited time that they can safely wait for a donor organ include; those with small hepatocellular cancers (6 months), those with hepatitis B-related cirrhosis on lamivudine treatment (mutants arise after 6 months) and those with fulminant hepatic failure (who usually die within 72 hours of listing if no donor organ is found).

Feedback

Please provide feedback directly to me via email at:

smunn@ahsl.co.nz

Submitted on 3/11/99 by:
Stephen Munn
Director,
New Zealand Liver Transplant Unit