Ethical Issues in Split Versus Whole Liver Transplantation
*Corresponding author: Peter G. Stock, firstname.lastname@example.org
Technologic advances in split liver transplantation have resulted in an ethical dilemma. Although splitting a liver maximizes the number of patients receiving an organ transplant, it may increase the morbidity and mortality for the individual patient receiving the split liver. This essay explores the ethical issues involved in the allocation of split livers, and proposes general policy guidelines for the allocation of split versus whole liver transplants.
Split liver transplantation (SLT) allows two recipients, in current practice usually an adult and a child, to benefit from one deceased donor liver. Recent comprehensive studies confirm that split liver transplants generally lead to less favorable results for individual recipients, but also lead to more individuals getting the benefit of a liver transplant. Surgeons' pioneering advances in the operating room have left a classic ethical dilemma in their wake: where and how should the transplant community draw a balance between the rights and interests of patient A (an adult recipient), who is at the top of the transplant list, and patient B (most likely a pediatric recipient), who is somewhere down the list and will get a timely liver transplant if and only if patient A shares the donor liver. The purpose of this essay is to explore this difficult issue and also to propose general ethical and policy guidelines for the use of split liver transplants vis-à-vis whole liver transplants.
Background Information on SLT
The donor shortage and development of SLT
The exigency in liver transplantation today is the shortage of organs. Results of liver transplants have steadily improved, thus making transplantation more attractive to more people, while at the same time, the prevalence of degenerative hepatic diseases, for which transplantation is the only effective remedy, has also increased (1). Unfortunately, the rate of liver donation continues to be relatively stagnant. Together, these factors ensure that the organ shortage will not only remain an intractable problem for the transplant community, but is likely to be exacerbated in coming years.
SLT is at the forefront of transplant surgeons' attempts to overcome the organ shortage. The results of these efforts are apparent: in the past, mortality rates for children on the transplant waitlist approached 40% in some locations, but today, with the increased use of split liver and pediatric living donor transplantation, mortality rates for pediatric recipients have declined precipitously (2). Depending on the age group examined, the results of SLT appear to be somewhat worse than whole organ transplantation (3). It might be expected that time to transplantation would be decreased with SLT providing a decreased risk of death while waiting for the recipient with lower priority, therefore providing a net benefit.
Outcomes associated with SLT
As the study by Merion and colleagues shows, transplantation with a liver split between an adult and pediatric recipient offers less favorable outcomes for the individual patient than whole liver transplantation (WLT) (4). Merion compared results from 907 split and 21 913 whole deceased donor liver transplants between January 1, 1995 and February 26, 2002 with each other as well as with survival rates for 48 888 patients waitlisted during this time. Over a 2-year period after transplantation, adult whole liver recipients lived an extra 5.1 months of life compared to patients still on the waitlist. Compared to similar patients on the waitlist in the same time frame, an adult who received a portion of a liver split for use between him or her and a pediatric recipient lived an extra 4.8 months of life, and the pediatric recipient lived an extra 2.8 months of life. The 2-year retransplant rate for adult whole liver recipients was 7%, and the commensurate retransplant rate for adult recipients of split livers was 13% (4).
Merion's study highlights the conflict at the center of this essay: while adult whole liver recipients lived an extra 0.3 months of life over adult split liver recipients, more people are alive when livers are split. With adult WLT, every 93 transplants used 100 livers (seven livers were used for retransplantation). However, when the split procedure was used, 100 livers were enough for 152 successful transplants (76 livers were split and 24 whole livers were used for retransplantation)—leading to an aggregate of 48 extra years of life lived over patients still on the waitlist, as compared to whole liver recipients' aggregate of 40 extra years of life lived over waitlist patients (4).
While Merion's study is the factual foundation for our inquiry, it should again be emphasized that there is considerable variation in results between transplant centers (3,5,6).
Information regarding SLT, where a deceased donor liver is split for use by two adult recipients (adult-adult SLT), is far less complete. Adult-adult SLT has been done only in small numbers. While there is variation among different centers, in the largest single center study to date, graft survival outcomes for adult-adult SLT were worse than those for whole liver transplants. Recipients of right lobe transplants fared about as well as adult recipients in adult/pediatric SLT, while recipients of left lobe transplants fared significantly worse (7). There are promising anecdotal accounts (8) of effective solutions to the complications inherent to this procedure, and it is likely that outcomes will continue to improve.
Discussion of the Implications of SLT
For reasons set out below, the authors of this paper suggest that under certain circumstances, splitting a liver between an adult and a pediatric recipient is ethically most appropriate. The focus of our inquiry is primarily patient survival rather than graft survival.
Competing objectives of organ allocation policy
Allocating organs ethically depends on a just compromise between several morally appropriate ends. The authors of a United Network for Organ Sharing (UNOS) white paper on the ‘UNOS Rationale for Objectives of Equitable Organ Allocation’ emphasize in their introduction that organ allocation policy ‘must strike a balance among competing, and often conflicting, objectives’ (9). The two main, potentially conflicting, objectives here are:
Objective 1: maximizing the number of patients receiving organ transplants, and
Objective 2: maximizing the individual patient's survival.
At the outset, it is apparent that in some contexts, there is no SLT dilemma because the two objectives do not conflict. Where a transplant center reports SLT outcomes that are the same as those for WLT, at that center, the first objective is satisfied without undermining the second objective. In other words, more people are getting help, and no one is getting hurt in the process.
Outside of this situation, however, there is a conflict, as the data in the section ‘Background Information on Split Liver Transplantation’ of this paper show. To resolve it, we start with commonly held ethical principles and traditions.
Principles governing the ethical allocation of organs
In the medical context, there has been considerable debate over whether physicians' primary loyalty is to their individual patient, or to society. For purposes of this inquiry (and considering historical precedent), the authors are prepared to err on the side of the individual patient. For example, according to the policies of the World Medical Association, physicians owe their patients ‘complete loyalty’ (10). In practice, this may mean that physicians will find themselves doing what is best for a patient even when it is not what is best for society. Clearly, however, there are limits to what costs society, and especially other similarly situated patients, should bear for the benefit of the individual.
Applying these principles and objectives to SLT and WLT
In discussing the appropriateness of SLT, we may look at the conflict between Objective 1 and Objective 2 through two separate inquiries. Each objective can now be qualified, in light of the above discussion on governing principles, that it will be pursued only so far as it does not lead to disproportionate costs. Thus, the two relevant objectives now are:
Modified Objective 1: maximizing the number of patients receiving organ transplants, so long as individual patients do not suffer disproportionate costs for societal benefit, and
Modified Objective 2: maximizing the individual patient's survival, so long as society does not suffer disproportionate costs for individual benefit.
WLT with a donor suitable for splitting fails Objective 1 because Merion's analysis shows that use of SLT leads to a greater number of successful transplants (63% more) than use of WLT alone, and more years of life lived (20% more) (4). The difficult judgment comes in analyzing whether SLT's societal benefits come at disproportionate costs to individual recipients. Merion's study shows that adult whole liver recipients would lose an average of 0.3 months of life over 2 years (a 6% decrease) if they instead received split livers. These patients are worse off, but their disadvantage is neither egregious in absolute terms, nor is it disproportionate to the 63% gain in the number of transplants, and 20% gain in the number of years of life lived. Graft survival rates are a bigger hurdle, and indeed the difference between WLT and SLT in this aspect is distinct (7% vs. 13% for adult recipients, respectively) (4). There is no easy resolution, and there is clearly room for further analysis. However, based on the more definitive measure of patient survival, SLT satisfies Objective 1.
SLT fails to satisfy Objective 2, though Merion's study shows that this failure is not dramatic (only a 6% decrease in individual life years compared with WLT) (4). Further, it is not apparent that WLT satisfies Objective 1 either, because of disproportionate costs. For every 100 donor livers, adult recipients of whole livers will gain an aggregate 10 more life years than they would have had the organs been split (4). At the same time, pediatric patients who would have received transplants had the livers been split, will lose 18 years of life over the 2-year period (4). The loss in extra years of life for pediatric patients will be twice as high as the gain for adult recipients of whole livers. This is more clearly disproportionate.
Looking at the results of the two inquiries, SLT arguably satisfies Objective 1 and fails Objective 2 marginally, while WLT decisively fails both objectives. On balance, SLT seems preferable to exclusive reliance on WLT.
This, again, is a difficult judgment, though it need not be so all circumstances. As stated previously, different transplant centers have different experience with the procedure. In some centers with very poor outcomes, SLT should not be encouraged. On the other hand, at this point in time, centers with comparable results for right trisegment/left lateral lobe splits to whole liver transplants clearly fulfill Objectives 1 and 2 more than exclusive reliance on WLT, and should be performed. However, adult-adult SLT more clearly fails to meet the second objective because of significantly higher morbidity and mortality rates associated with this procedure (7).
Livers for transplantation are offered to a patient with the highest priority. A patient with the highest priority can accept or refuse the offer for transplantation without prejudice. One question is whether the patient can decide if he or she would accept only the whole liver or the SLT. One objection to greater use of SLT is that it is coercive to limit patients at the top of the transplant list to a split liver. Apart from whether this is justified because of the corresponding benefit to others, the problem is at least partially addressed by affirming patient autonomy.
Patients have the unequivocal right to refuse any organ offered to them. Regardless of how patients are affected by SLT, in all stages of the transplantation process, physicians should make decisions in partnership with their patients. While this does not mean that individual patients are entitled to decide how a donor liver is to be used—the organ procurement system is based on stewardship, not ownership—it does mean that patients are entitled to make effective decisions about their health.
Further, at all times, patients are entitled to receive complete and accurate information about their care. Specifically, doctors and others must inform a patient, as accurately as possible, of the risks attending SLT, and their center's experience with the procedure. An area of further investigation is to develop tools to allow patients and physicians the ability to decide to accept these split livers or await the offer for a whole organ.
Recommendations for Split Versus Whole Liver
We will summarize these ethical considerations in the context of the concluding recommendations (in italics below) proposed in the UNOS Ethics Committee White Paper on ‘Split vs. Whole Liver Transplantation’ (11).
- 1Transplant centers and OPOs have a clear ethical obligation to maximize the number of potential recipients of donated organs. Splitting medically suitable livers is ethically proper. Given the net benefit of splitting as demonstrated in Merion's paper, split livers should be performed in the 15% of livers ideally suited for splitting, as identified by objective tests and benchmarks (12). A question remains if the liver from the donor should be directed to centers and patients who would be willing to split such a liver.
- 2Patients have the clear and unequivocal right to refuse an offered organ, including a liver segment. If an adult at the top of the list who receives the primary offer of liver has not consented to split a liver, which is ideally suited for splitting (only 15–20% of livers), then the liver should be offered to the next person on the local list who consents to splitting the liver. This currently pertains only to the right trisegment/left lateral lobe splits until such a time a societal benefit is demonstrated for adult-adult SLT. This policy is also only justified at centers that have acceptable graft and patient survival with the right trisegment/left lateral split (see point 4 below). In this case, the adult with the highest MELD who received the primary offer, but has not consented to splitting a suitable liver, would maintain their position based on MELD score. They would be offered the next whole liver, which is not ideally suited for splitting (>80% of all deceased donor livers). Patients who decide against accepting a split liver should nevertheless be offered the option at the time a split liver becomes available, insofar as patients may change their minds with changing circumstances. If children receive the primary liver offer based on their high PELD score (the more frequent scenario), the right trisegment should be offered to the adult at the top of the list (based on MELD). In this scenario, most adults will accept the right trisegment. If the segment is refused, it would be offered to the next adult on the local list based on high MELD score. Ideally, the split livers should be shared between different centers sharing a local list, so that the segment is offered to the next person on the local list based on MELD/PELD score. Sharing segments between centers requires expertise for splitting at all centers involved, as well as excellent communication between the different centers with regards to the planned technical aspects of the split (i.e., which segment will get the celiac trunk, which segment will get the main bile duct).
- 3Patients have the right to exercise informed consent concerning risks they are willing and unwilling to accept regarding their own care. This should be based on the best currently available information regarding: The potential of the split liver procedure for increased morbidity and longer hospitalization; and experience with SLT versus WLT in the transplant center where they are listed and in other transplant centers.
- 4All parties involved in the transplantation process must understand that there is no claim of ownership of an organ by a potential recipient, transplant center/program or transplant surgeon. There is, however, a stewardship responsibility inherent in this process. Each person involved in the recovery, placement and transplantation of an organ is a guardian rather than owner of that particular organ. The responsibility of stewardship should entail utilizing the donor liver in a manner, which increases the number of available organs without undue risk to the individual patient. For centers with comparable graft and patient survival, split livers (right trisegment, left lateral for a child) should be performed in the 15% of livers, which are ideally suited for splitting. However, for centers that do not have comparable graft and patient survival with the right trisegment/left lateral lobe split, this action could not be justified. Similarly, for the ‘true’ split, this action is not currently justified secondary to the significant morbidity and mortality associated with transplantation of the smaller left lobe. In these latter cases, the risk to individual patient survival outweighs the potential benefit of increasing the number of patients receiving an organ transplant. These circumstances will change with technologic advances.
- 5An overriding responsibility of transplant surgeons is to inform potential recipients of the current practices of their program regarding SLT including the potential for increased morbidity, the possibility of further invasive interventions and the prospect of longer hospitalizations, as well as supply outcome data regarding SLT versus WLT. To maximize utilization of such scarce resources, this discussion should take place at the time of listing or several months prior to the patient ascending to the top of the transplant list. If recipients are fully informed at an appropriate time regarding the potential advantages of receiving a split graft (i.e., only ideal donors utilized for split livers), these incentives will be properly weighed against the potential complications/risks. It is imperative that the consent process occurs early in the transplant process to facilitate informed consent, without the duress that accompanies the period immediately preceding the liver transplant. If patients are made aware of the fact that only high quality organs (i.e., young deceased donors with low BMI) are used for splitting with a child, the slightly increased morbidity of the split would be counterbalanced by the higher quality of the organ. Similarly, during the early consent process, it should be emphasized that the left lateral lobe made possible by splitting the liver will be used to benefit a child. An early discussion and documentation of consent for receiving a segment will also facilitate the rapid placement of the scarce donor organs.
Finally, policies regarding the allocation of split livers versus whole livers should be continually reevaluated with technologic advances. Ultimately, the moral inquiry is about balancing, and to do so effectively requires accurate information.