Psychosomatics 43:347-353, October 2002
© 2002 The Academy of Psychosomatic Medicine
Some Ethical and Psychiatric Aspects of Right-Lobe Liver Transplantation in the United States and Japan
Owen S. Surman, M.D.,
A.B. Cosimi, M.D.,
Isao Fukunishi, M.D., Ph.D.,
Tatsuo Kawaii, M.D.,
John Findley, M.D.,
Yoshiaki Kita, M.D., Ph.D., and
Masatoshi Makuuchi, M.D., Ph.D.
Received Dec. 3, 2001; revisions received April 16 and May 10, 2002; accepted May 22, 2002. From the Transplant Unit and the Department of Psychiatry, Massachusetts General Hospital; the Tokyo Institute of Psychiatry; and the Department of Surgery, University of Tokyo Hospital. Address reprint requests to Dr. Surman, Department of Psychiatry, Massachusetts General Hospital, WACC 815, 15 Parkman St., Boston, MA 02114-3117; osurman{at}partners.org (e-mail).
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ABSTRACT
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Cadaver sources are insufficient for the increasing demand for liver transplantation. Right-lobe liver transplantation from living donors is fully developed in Japan and has been rapidly increasing in the United States during the past 2 years, although donor risk is greater than in other types of solid organ transplantation. The authors examine the psychiatric and ethical aspects of right-lobe liver transplantation in light of cultural differences between the United States and Japan.
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INTRODUCTION
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Solid organ transplantation from live donors began in 1954, during an era when transplantation biology had not yet afforded a means for effective use of cadaveric sources. In that year, Dr. Joseph Murray successfully transplanted a kidney to a recipient from his twin brother.1 With improved methods for immune suppression, transplantation from cadavers later became the principal source of organs in the United States, but the quantity of organs from this source is now insufficient to meet growing demand.
Right-lobe liver transplantation from living donors is a recent development that has proved lifesaving for many patients. This technological advance was achieved in the mid-1990s in Japan, where cultural factors make cadaveric transplantation an uncommon event.2,3 More than 1,500 adult-to-adult liver transplants have been performed in Japan, with no reported donor mortality. In one series, no major postoperative surgical complications were reported among 41 right-lobe donors.4
Approximately 900 living donor liver transplant operations were performed in the United States between 1991 and January 2002, according to the Scientific Registry of Transplant Recipients (June 2002 presentation to the Board of Directors of the Organ Procurement and Transplantation Network/United Network of Organ Sharing by Hui-Hsing Wong, M.D., J.D., Office of Special Programs, Health Resources and Services Administration). Two known donor deaths were reported, and a third occurred soon thereafter (two right-lobe donors and one donor of the left lateral lobe). In one case, adverse effects led to subsequent successful liver transplantation in the donor. Trotter et al.5 estimated a 5% risk of biliary leaks among donors and a 9%–19% risk of complications related to major abdominal surgery. In a review of reports of right-lobe liver transplants, Beavers et al.6 found rates of donor morbidity ranging from 0%–67%. A recent report of severe pulmonary embolism in a donor7 underscored the risk of medical complications and need for an international registry to document adverse events. The American Association of Transplant Surgeons and the National Institutes of Health are currently seeking to develop such a registry.
The actual rate of mortality from adult-to-adult right-lobe liver transplantation has not been established.8 Despite the lack of a mortality rate, one recent report suggested that the American public may accept a substantially greater level of risk than is tolerable to the transplantation surgery community.9 It is also possible that the public may prove less accepting as reports of actual donor injury appear in the press. From a psychiatric and ethical standpoint, right-lobe liver transplantation from living donors must be seen within a broad social context. The emergence of this technology in two different cultural settings allows a comparative perspective in examining its psychiatric and ethical implications.
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EVOLUTION OF TRANSPLANTATION POLICY AND PRACTICE
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Japanese expertise in live-donor transplantation of liver lobes evolved from lack of acceptance of cadaveric transplantation in Japanese society. In the United States, cadaveric transplantation was facilitated by the acceptance of criteria for brain death. The Japanese public has been resistant to this concept, partly because of a greater concern among the Japanese about defining the end of life. Nudeshima,10 a leading Japanese medical ethicist, has explained that traditionally, "a person was ... recognized as truly deceased only after a long process of funerary and death anniversary rites." Americans, in contrast, tend to have greater concern about medical issues dealing with the beginnings of life.
Japanese surgeons performed cadaveric donor transplantation for the first time in 1964. Liver transplantation and lung transplantation were each accomplished at that time. Cadaveric donor renal transplantation was introduced in 1967.11 Great controversy developed in the following year when a Japanese thoracic surgeon, Jiro Wada, at Sapporo Medical University, successfully transplanted the heart from a young drowning victim. The recipient survived for 8 months, which at that point was among the longest periods of survival that had been accomplished worldwide. Unfortunately, many in Japan concluded that the survival was prolonged because the donor was not truly dead when his heart was removed. This urban myth provoked a journalistic uproar. Dr. Wada was accused of murder, although he was never prosecuted.
Ultimately, Japan's major legislative body, the Diet, provided a solid legal basis for cadaveric transplantation. The Diet does not endorse the use of brain-death criteria for determination of death. However, there is an exception—the Sekine revision—for persons who have given prior consent in writing and who subsequently meet brain-death criteria.12 Truog13 has suggested that this provision is an attractive alternative to rules requiring brain death in the donor. Truog wrote: "When considering the transplantation of vital organs could we shift the central question from, ‘Is the donor dead?’ to ‘Do we have the donor's permission, and/or would donation significantly harm the donor?’ " Action by the Diet has not, however, changed the climate for cadaveric transplantation in Japan.
Japanese people are not unique in their concern about the brain-death paradigm. Youngner et al.14 reported the results of a survey of U.S. health care professionals, many of whom did not believe that brain-dead patients were "really dead." They believed that the patients were dying or damaged irreparably. Capron15 observed that, "this confusion is reinforced when hospital personnel state that ... ‘life support’ is being removed from such patients." Ambiguity and ethical debate about the concept of brain death have not, however, impeded the development of cadaveric transplantation in the United States.
Given that there is far less emphasis in Japan than in the United States on formal religion and spirituality, other factors are evidently important in restraining performance of cadaveric transplantation. Nudeshima16 has explained that there is less public trust in Japan about medical practice and self-regulatory procedures of the medical establishment. Taken together, the traditional orientation to end-of-life matters and the public perception of medical practice have restricted cadaveric transplantation in Japan. Few Japanese citizens have signed donor cards. Most are unwilling to donate their organs in the event of brain death. Some recipients of cadaver organs are secretive about their transplants because they fear disapprobation.17 Japanese surgeons have been understandably reluctant to perform cadaveric transplantation. Only about 100–200 such procedures are performed annually for patients with end-stage renal disease. The Japanese experience in this area supports the notion expressed elsewhere that for some "cases in which science appears to be driving policy, it is really politics driving science."18
Liver-lobe transplantation from live donors thus became the only means of significantly prolonging life for Japanese victims of liver failure. Japanese surgeons who perform these procedures have substantial training and skill. Moore,19 writing about the ethical implications of transplantation, has referred to the level of expertise in a particular procedure as "field strength." Skill levels, or field strength, in the same type of hepatobiliary surgery are less uniform in the United States.
Variations in field strength are influenced in part by socioeconomic factors. Japan has one of the world's most comprehensive national health care plans. Hospitalization periods after transplantation are considerably longer in Japan—3 months for the recipient, 1 month for the donor—than in the United States. In Japan, patients are medically able to return to work at the time of discharge. Therefore, relatively little economic incentive exists for Japanese surgeons to take on the attendant challenges of liver-lobe transplantation. In contrast, patterns of health care practice in the United States make liver transplantation very attractive to major medical centers. In light of intense competition among American transplant centers, there is considerable pressure to offer adult-to-adult living donor liver transplantation
Moore's major concern regarding therapeutic innovation was related to the ethical climate of institutions.19 His forthright cautionary comments addressed circumstances in which "institutional reputation, fame, surgeon ego, municipal pride and chauvinism become the true objectives of the procedure." He added that "these matters of ethical climate might appear difficult for the lay public or municipal bodies to judge."
Cronin et al.8 concluded that some of the U.S. centers performing these procedures may have had insufficient experience. Busuttil20 advocated for a five-point certification program for transplant centers that intend to offer adult-to-adult living donor liver transplants. The certification process would have federal oversight through linkage with the Centers for Medicare & Medicaid Services. Approved transplant centers would be required to establish the need (for a new center) and the availability of essential resources for living donor transplantation. They would have extensive experience in hepatobiliary surgery, a comprehensive approach to informed consent, and a system for recording donor outcome.
In addition to cultural differences between Japan and the United States, differences in genetic factors significantly affect surgical practice and operative outcome in the two countries. The Japanese have leaner body mass, which reduces the technical demands of right-lobe liver transplantation and also makes left-lobe donation a feasible alternative in some adult-to-adult living donor transplants.21,22 The smaller mass left-lobe allograft makes the procedure less risky for the donor, but in the United States this procedure has provided insufficient liver mass for the recipient. For pediatric patients, partial left-lobe transplantation utilizing only segments 2 and 3 has been a mainstay of liver transplantation in both countries since 1989.23
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RECIPIENT SELECTION
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Indications for liver transplantation are similar in the United States and Japan. Hepatitis C, which currently accounts for 60% of liver failure in the United States, is far less common in Japan than in the United States. The Japanese have a much lower prevalence of drug abuse, and alcohol produces less liver toxicity in the Japanese because of genetic differences in alcohol dehydrogenase. Transplant candidate selection in both countries is determined by the capacity for medical benefit.
In the United States there has been a significant shift in distribution of medical resources since kidney transplantation first became feasible in the 1960s. Availability of treatment for renal failure was severely limited, and a social-worth or "life-boat" ethics model governed the choice of recipients. Patients with other systemic disease and those over age 50 were excluded.24 Congress passed legislation to support treatment of end-stage renal disease in 1972. Thereafter, the ethical climate for distribution of resources became more equitable. This trend was subsequently enhanced with the passage of the Americans With Disabilities Act. However, those with a limited prognosis are excluded. For example, the United Network for Organ Sharing considers a patient with a single lesion of hepatocellular carcinoma eligible for transplantation only if the lesion is less than 5 centimeters in diameter.25 There remain significant differences among U.S. transplant centers in regard to selection of patients with psychiatric disorders.26,27
Trotter et al.5 have reported that 10% of patients with end-stage liver disease die while waiting for a suitable organ. Priority in candidate selection has been based on urgency and time waiting. Recently in the United States, the United Network for Organ Sharing adopted the Model for End-Stage Liver Disease, which is based on probability of dying while waiting for a suitable organ.28 The change from previous reliance on the Child Turcotte Pugh Grading of Liver Disease Severity and time waiting increases the emphasis on urgency.28 The new policy has substantially altered the status of some patients awaiting a cadaveric liver. For some there is benefit; for others, increased suffering.
Some medical ethicists consider that fairness in "tragic choices" is negatively affected when the system for distribution of scarce resources becomes complex.29 Emphasis on probability of death within the short term may also result in preferential treatment of patients with less likelihood for favorable long-term prognosis and productivity. Availability of living adult-to-adult liver transplantation offers relief for this category of patients. Right-lobe transplantation is less well suited than cadaveric transplantation for patients bound to the intensive care unit who require a larger hepatic mass for survival.5
An additional question is whether living donor transplantation should be offered to recipients who have a low prognosis for long-term survival and a good quality of life as currently measured. In both the United States and Japan right-lobe transplantation from live donors has been extended to some cancer patients who are currently ineligible for cadaveric transplantation. In the case of allograft failure, these patients are then placed at a priority on the cadaveric transplant list. From a utilitarian standpoint, one may ask as well whether extensive medical resources should be deployed to sustain life in marginal transplant candidates with multiple comorbidities. For example, a recipient may have liver failure from hepatitis C as well as comorbid adult diabetes mellitus, renal insufficiency, and a past alcohol dependency. Any of these conditions could progress or recur after otherwise successful living donor transplantation. A recent survey of 150 individuals presenting for routine primary care found support for live-donor liver transplantation in candidates with a 55% rate of projected survival.9 Methodological limitations related to survey techniques make it impossible to generalize from these data, but the findings support a need for further investigation.
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LIVING DONOR PARTICIPATION
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The ethical climate for living organ donor volunteerism in the United States has been increasingly favorable since its inception. In the 1960s there was general concern in the medical community about risk to the donor and also about underlying factors in donor motivation. A qualitative naturalistic clinical study by Fellner and Marshall30 documented the genuine altruism and psychological benefit among 12 kidney donors. Subsequent studies confirmed this finding. Predictors of negative donor experience included pretransplant evidence of ambivalence or of "low happiness and low self-esteem."31 Postoperative donor experience was more likely to be negative among "black sheep donors," those who were less close to the recipient, and those who received less gratitude.32
While the American medical community regarded living-organ donation with initial skepticism, the American public found it reasonable, and many expressed the willingness to volunteer.33 Currently in the United States there is broad acceptance of even living donor transplantation involving nonrelatives. New approaches include donor-swap programs, nondirected donation, and directed donation to a kidney transplant waiting list when highly motivated family donors prove immunologically incompatible with the intended recipient.34 Donation of a lobe of lung by each of two participants has been provided for selected lung transplantation recipients.
The practice of segmental left-lobe liver transplantation was first introduced at the University of Chicago. Singer et al.23 discussed the ethical aspects of this procedure and allowed for a 6-month delay before its inception. This delay gave the opportunity for widespread consideration and comment within the medical community. Right-lobe liver transplantation presents a further increase in donor risk, but it has evolved without a similar opportunity for broad preliminary discussion and debate.8,35 Cronin et al.8 have contended that right-lobe transplantation has proceeded too far too fast.
Urgency for pressing ahead with liver lobe transplantation is provided by the 10% incidence of death among liver-transplant candidates waiting for a suitable organ.5 In practice, a referral for liver transplantation is facilitated by the treating hepatologist, who in turn faces a progressively ill patient with diminishing opportunity for life-saving intervention. Family members of patients with end-stage liver disease are increasingly well informed about the possibility of right-lobe donation and actively seek out that option. The current favorable climate for organ donation in the United States encourages organ donation from spouses and friends and sometimes from strangers. Olbrisch et al.36 have identified six classes of organ donors: genetically related donors, emotionally related donors, Good Samaritan donors (directed), Good Samaritan donors (nondirected), vendors, and organ exchangers. Sale of organs is prohibited in all but a few countries. All of the other approaches to organ donation are approved in American practice. In Japan, organ donation is only acceptable within the context of a biological relationship.
Current practice guidelines require that the donor be fully willing, independently motivated, and fully informed.34 The depth of psychosocial evaluation and the sophistication with which it is accomplished depend on the training, skill, and experience of the psychiatrists, psychologists, and social workers engaged in this process. Under the best of circumstances, the donor's actual motivations and intent are often difficult to know.8 Olbrisch et al.36 have cautioned that the donor may engage in impression management, concealment of important health information, or, less commonly, deception about financial incentives.
Some potential donors who volunteer initially to learn more about the process may subsequently feel that they cannot gracefully withdraw. Some examples from clinical practice illustrate the possibility for varying degrees of coercion. In one case, a potential kidney donor received an initial information packet from the spouse of the intended recipient. In that case, the donor's confidentiality was compromised when the recipient's spouse was able to obtain advance notice of the donor's medical eligibility. In a more dramatic situation, a kidney donor who had come to the United States from abroad was able to confide with the help of a native-language interpreter that she feared that she might "disappear behind the light" if she changed her mind about donating.
The donor may be inalterably motivated or uncomfortably ambivalent. "Why wouldn't anybody want to do this?" one right-lobe donor confidently stated on postoperative day 3. After providing informed consent, another donor quietly asked one of the authors (O.S.S.), "What would you do?"
Some potential donors are unfailingly guarded about sharing their concerns. This phenomenon is especially likely in Japan, where importance is placed on keeping emotions in check. Fukunishi37 has described the use of house-tree-person projective testing under these circumstances. Some donors drew truncated trees, indicative of a perceived threat to bodily integrity.
It would be interesting to know to what extent such findings differ for highly altruistic donors and for those motivated chiefly by duty to family, which is an especially compelling value in Japanese society. Under all circumstances, it is essential that the donor understand the transplant team's willingness to help donor candidates withdraw gracefully if such action is best.
When we meet with altruistic transplant donors, they are primarily focused on needs of the intended recipient. Transplantation psychiatrists familiar with right-lobe liver donation have found that donor candidates often say that they would be willing to proceed even if risk of their dying were far beyond the range acceptable to the medical community. In the primary care survey by Cotler et al.,9 60% of those who indicated a theoretical willingness to be a partial liver donor preferred to donate and die rather than to abstain from donating and see the recipient succumb to liver failure. It is difficult to know to what extent this represents true acknowledgment of risk versus the expectation that the surgeon will ensure that none of the potential adverse outcomes will come to pass. In effect, the donor's internal dialogue may be, "The surgeon would not be doing it if it were not all right for me to participate."
Research on informed consent in clinical trials has revealed that volunteers typically defer to the investigator.38 The surgeon's willingness to perform surgery on a right-lobe liver donor may be taken as tacit reassurance of the donor's safety.35 The donor may acknowledge risk but expect a favorable outcome. This may explain the finding by Trotter et al.39 that 15 (63%) right-lobe donors encountered greater postoperative pain than expected. These authors subsequently modified the informed consent process and encouraged donors to meet with previous donors with similar life circumstances. They also share with donors the results of a survey on donors' postoperative quality of life.40
Given the readiness of people to come forward as right-lobe donors, the attendant risks of the process, and the implicit trust by those who donate, it is important for clinicians to carefully scrutinize the general health of the donor and to carefully assess the prognosis of the recipient in terms of both survival and expected quality of life. Moore,19 concluding that ethical considerations for innovative procedures are essentially probabilistic, wrote: "What is the likelihood of harm being done, as opposed to the likelihood of good accruing to the patient? Here is an ethical problem that comes down to mathematical calculation of statistical likelihood."
There is little available information regarding psychological experience after right-lobe liver donation. In a prospective study that controlled for the type of donor surgery, Fukunishi et al.4 found a 10% (four of 41 cases) incidence of psychiatric complications among adult-to-adult liver donors at 1 month after transplantation. The prevalence rate of psychiatric complications was significantly lower—1% (two in 234 cases)—among kidney donors. To our knowledge, no comparative data for the U.S. experience are currently available. Trotter et al.39 used the Medical Outcomes Study 36-item short-form survey to assess quality of life among 24 right-lobe donors at 4–37 months after the operation. Twenty-three donors (96%) had returned to their previous job, six donors (25%) indicated that they had not made a complete recovery, and 10 (42%) reported changes in body image. All 24 donors indicated that they would donate again. The authors were enthusiastic about the overall outcome. In another survey, Beavers et al.40 found that 100% of 27 donors would both donate again and recommend the operation to others who were thinking about donating. One must be aware of cognitive dissonance (uncritical reaffirmation of previous choices) in reports of this type.
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ETHICAL CONSTRUCTS
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Ethical paradigms ultimately conflict with one another.41 Current policy regarding living donors places emphasis on autonomy and also on nonmalfeasance.34 The inevitable conflict between these two perspectives at the extreme is dramatized in statement made by Dr. Thomas Starzl more than two decades ago at a national psycho-nephrology conference directed by psychiatrist Norman Levy, M.D. (New York, Oct. 1978). Dr. Starzl, who was opposed to living organ donation, was challenged about whether he would choose to give a kidney to a son with end-stage kidney disease. He replied, "I would give him my heart!"
American medicine is primarily guided by an emphasis on individual rights; however, other communitarian principles also require attention.42 In the case of Dr. Starzl's theoretical gift for his son, individual rights are in extreme conflict with overall social good. The decision to go forward with living partial liver donation has ultilitarian value to the extent that the donor's risk is in balance with expected net social benefit.
In acts of altruism, an individual behaves in a fashion that is potentially disadvantageous to self but advantageous to others. From an evolutionary perspective such behavior runs counter to the "selfish gene" hypothesis of natural selection.43 Sober and Wilson44 have argued, however, that group selection is a basic factor in human evolution. Groups that rank high in altruism compete successfully with other groups that have fewer altruists. This argument presupposes that altruistic acts contribute to social advantage.
The development of guidelines for right-lobe liver donation requires careful consideration. Is distributive justice served when an adolescent donor is at risk on behalf of a recipient who is decades older? What of instances in which a single parent is at risk on behalf of a recipient with limited future productivity? The ultimate shortcoming of placing any live donor at risk is a steady stimulus to scientific advance in emergent areas of xenografting and tissue engineering.45
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- Hashikura Y, Makuuchi M, Kawasaki S, Matsunami H, Ikegami T, Nakazawa Y, Kiyosawa K, Ichida T: Successful living-related partial liver transplantation to an adult patient (letter). Lancet 1994; 343:1233-1234[Medline]
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This article has been cited by other articles:
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O. S. Surman, I. Fukunishi, T. Allen, and M. Hertl
Live Organ Donation: Social Context, Clinical Encounter, and the Psychology of Communication
Psychosomatics,
February 1, 2005;
46(1):
1 - 6.
[Abstract]
[Full Text]
[PDF]
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ABSTRACT
INTRODUCTION
