Why choose a living donor transplant? According to the American Liver Foundation, more than 18,700 people in the United States are on the waiting list for a donor liver, while fewer than 5000 cadaveric livers are available for transplant each year.⁷ The need for donors is striking: in 2001, for example, more than 1500 patients on the waiting list died before receiving a liver transplant.⁸ A large group of patients who remain on the list from year to year grow sicker, as the likelihood of a healthy outcome when a donor liver does become available declines. Of the more than 2.7 million people who have chronic hepatitis C virus infection, approximately 20% to 30% will need a liver transplant, another indication of the growing disparity between supply and demand.⁸

The introduction of immunosuppressive agents such as cyclosporine in the early 1980s dramatically improved the feasibility of transplant procedures. Pediatric liver transplants have been performed successfully since 1967. A shortage of pediatric cadaveric livers and the high mortality rate of children on the waiting list pushed transplant surgeons to consider adult-to-child LDLT (typically with a parent or other family member serving as the donor). The success of this procedure, and the increasing disparity between the number of adults on the waiting list and the number of cadaveric livers available, made the prospects for adult LDLT appealing as well as socially and ethically acceptable. In fact, LDLT has 2 main advantages; the availability of a donor liver without the need to wait until the patient's name arrives at the top of the waiting list for cadaveric organs, and the ability to thoroughly evaluate the donor and insure the health of the donor organ.⁹

Although nearly all patients on the waiting list for cadaveric organs can be considered candidates for LDLT, only 5% to 15% may ultimately pass the strict criteria and undergo the procedure.¹⁰ Generally, recipients of LDLT are less ill than recipients of deceased donor grafts. In deceased donor transplantation, patients receive a whole liver, whereas in right lobe LDLT they receive about 55% of the donor liver and accompanying structures and vasculature. Much less frequently, in special circumstances such as when the donor is larger than the recipient, a protocol using the left lobe may be preferable. In adult-to-child LDLT, the child typically receives a segment of the left lateral lobe representing about 20% of the donor liver.

With a right lobe adult LDLT, both the donor and the recipient are left with approximately half of the normal adult liver volume, which adds some risk to the procedure. In general, the added risk for the recipient is compensated for by their better health status at the time of the transplant. Because of the remarkable regenerative capacity of the liver, both hemi-livers rapidly regenerate to reach the volume of a normal human liver. However, in the donor, the left lobe will expand to yield this volume, resulting in one large left lobe, whereas the recipient will have an oversized right lobe. Available data suggest that this does not compromise liver function in either the donor or the recipient. Typically, the remaining liver doubles in size. It reaches greater than 85% of initial hepatic volume within 1 week after transplant, and regeneration is complete within about 3 months.³ Older livers generally do not regenerate as quickly.¹¹

At present, about 15% of liver transplants are performed using a liver from a living donor. In comparison, more than half of kidney transplants use organs from living donors. It is doubtful that the percentage of LDLTs will increase much; rigorous donor selection is necessitated by the inherently more dangerous liver donation as compared with kidney donation. Many factors enter into the decision to become—and to accept—a potential donor. The transplant program must make a team decision about the eligibility of a donor based on careful evaluations, painstaking attention to detail, and considerable discussion by physicians, surgeons, psychologists, psychiatrists, and social workers. Acceptance of adult LDLT as a viable alternative, the right of a person to become a donor, and permission for the transplant team to perform the procedure, are ultimately not only personal decisions, but medical, surgical, psychological and societal decisions as well.

Educating patients about being a living donor At the center of the debate about organ donation is the immutable belief that the decision to donate must be completely voluntary. It is the difficult responsibility of the transplant team and the donor advocate to rule out any evidence of coercion. For this reason, most transplant teams prefer the donor to be a close relative or at least a very close friend of the recipient. Good Samaritan donations are rare and controversial, but can be considered in some circumstances.

The three factors crucial to ensuring that organ donations are voluntary are educated informed consent, the inclusion of an independent donor evaluator, and the requirement that the donor is the one who initiates the evaluation process. Educated informed consent demands that the prospective donor clearly understand all aspects of the evaluation and procedure and, in particular, the potential risks. Donor candidates tend to be very altruistic people who have good intentions, and may too often underestimate the risk to themselves, despite appropriate efforts at education and counseling.

The transplant team must always weigh the potential risk to the donor against the risk that the recipient could die before becoming eligible for a cadaveric organ. Whether to expand the definition of what makes an acceptable donor when the recipient has only a 50% chance of surviving until a donor organ becomes available is only one of the difficult questions that must be deliberated on a case-by-case basis.

Who is an acceptable donor? The age cutoff for living liver donors varies from program to program and state to state, but typically donors are between 21 and 55.³ In general, donors should be healthy individuals without liver disease, coronary artery disease, or cerebrovascular disease, and they should have an emotional link to the patient. In this regard, the evaluation process for a donor is more intensive than for a recipient, as physicians aim to "first do no harm."

Of the donor candidates who present for evaluation, 15% to 45% may be suitable donors.³ Candidates are most often excluded because of blood type incompatibility or a red flag in their medical history, such as diabetes, elevated cholesterol, kidney problems, or hypertension. Virtually any relevant abnormality will result in exclusion. Another group of prospective donors will be filtered out based on psychological issues, and about half of donors who are finally offered the opportunity to donate will exclude themselves. The findings of a National Institutes of Health conference held in 2000 revealed that about half of potential donors were accepted as candidates and 37% of those chose not to donate.⁸ Thus, only about 20% to 25% of potential donors ultimately participated in a transplant.

The goal of donor candidate evaluation is to identify contraindications as early as possible and with a minimum of invasive testing.² Donors should be given multiple opportunities to reevaluate and reaffirm their decision throughout the evaluation process.² The transplant team needs to carefully and completely explain the short-term risks of living liver donation and advise potential donors that the long-term risks are unknown.⁸ In addition to receiving a description of the procedure itself, the potential donor may benefit from a drawing or picture of the scar that will result.¹² As soon as a potential donor begins the evaluation process he becomes a patient who is entitled to the same privacy considerations as any other patient.¹² For example, the donor should have a separate medical chart, and all information regarding the evaluation should be kept confidential.

TABLE 1: UCLA adult-to-adult liver living donor selection protocol.

Evaluating a potential donor The donor evaluation comprises 6 main components: blood type compatibility; a general medical assessment of all organ systems; a more detailed evaluation of the liver, possibly including liver biopsy; a psychological and psychiatric assessment of the donor; a look at the donor's family and support system; and financial considerations (see Table 1 ). When a prospective donor voluntarily seeks an evaluation, the first step is to determine blood type compatibility. Human leukocyte antigen testing, as performed for bone marrow transplantation, is not necessary. Assuming a donor's blood type is compatible, a screening interview (often by phone) and then a complete medical history and general medical evaluation will follow.

The prospective donor's primary care physician can help in conducting these early assessments. The initial assessment will also include standard laboratory tests to establish baseline values, including liver function tests, blood chemistries, hematology and coagulation profiles, urinalysis, serum alpha-fetoprotein level, and tests for carcinoembryonic antigen, hepatitis, cytomegalovirus, Epstein-Barr virus, and HIV.²

If the donor undergoes and passes a medical evaluation outside the transplant program, the transplant team may still repeat some of the tests. Throughout the evaluation period, the prospective donor will be assigned an independent transplant hepatologist, who is not on the transplant team, who will examine the donor and serve as his or her advocate to ensure that the donor is physically and psychologically fit to donate, understands the procedure, the risks, and the follow-up protocol, and is not being coerced in any way.³ After the initial laboratory studies, the prospective donor will undergo a battery of psychological tests and detailed interviews with a psychiatrist, a social worker, and other members of the transplant team.

Donors must be healthy, close to their ideal body weight, not taking many medications, and not have had abdominal surgery. Additionally, their liver must be large enough to temporarily support the donor and the recipient with only half of its initial volume. Contraindications include obesity, hepatitis, use of oral contraceptives, a history of smoking, HIV infection, substance abuse, a coagulation disorder, and psychiatric illness.²

The final step in donor evaluation is radiologic or histologic examination of the liver. Generally, most donors undergo only CT or MRI to evaluate liver substance and vasculature, but some donors may require more invasive testing such as liver biopsy, liver angiography, or endoscopic study of biliary anatomy.² Pulmonary function tests and echocardiography are also commonly done. Liver biopsy to exclude parenchymal abnormalities or macrovesicular steatosis is routinely performed at some centers and not at others.⁴

What are the risks?

TABLE 2: Complications reported in donors for living donor liver transplantation.

The main risks of adult LDLT are those associated with any major surgery, including bleeding, infection, a negative reaction to the anesthesia, and, rarely, death (see Table 2). Complications typically occur in 15% to 30% of donors.³ Pain is the most common postoperative complication, but rarer complications such as pneumonia, bleeding, infection, or formation of blood clots can also occur and may prolong the hospital stay and slow recovery and return to daily activities and work.

Biliary leak is one of the more common complications.² Because the donor liver is resected, there is a risk of bleeding and bile leakage from the cut edge. This is usually treatable without surgery. Other common complications include hernia and bowel obstruction. Problems with bile duct function can pose a serious, long-term risk. Half of the donor's bile duct is removed, and half is left behind. Any blockage of bile flow from the remaining portion may damage the liver. The estimated risk of death from right hepatectomy is 1 death in 300 patients undergoing right lobe donations (0.2%-0.5%).⁶ Complications are more common for the recipients.

In a study of living related pediatric liver transplant patients, biliary complications occurred in 38% of transplants.¹³ Strictures accounted for 44% of the biliary complications in half of the transplant recipients, and leaks were responsible for 56% of the complications. The study reported that organ rejection and length of hospital stay were significantly greater in patients with biliary complications, although they were not linked to decreased patient survival.

Follow-up care The donor can expect to spend 5 to 7 days in the hospital, followed by 2 to 6 weeks of recovery at home. Donors should be able to return to full-time activity at about 3 months. Most transplant teams provide follow-up care for at least a year, although an effort is under way to require transplant centers to provide longer-term follow-up, perhaps for up to 10 years. This proposal presents several complicating factors. For example, some donors may want to end their association with the transplant center and not participate in additional follow-up care. Financial issues are also a key consideration. Should the recipient's health insurance continue to fund donor care beyond a year? What if the recipient changes insurance coverage; could the new plan be required to pay for long-term follow-up care for a "preexisting" condition? Other issues relate to the willingness of the donor's health insurance to cover late complications related to the transplant and the ability of the donor to get new health care coverage following LDLT.

This article was written by Vicki Glaser in consultation with Drs Brown and Everson.

Drs Brown and Everson disclose that they have no financial relationship with any manufacturer in this therapeutic area.

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4. Brown RS Jr, Russo MW, Lai M, et al. A survey of liver transplantation from living adult donors in the United States. N Engl J Med. 2003;348: 818-825.

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7. American Liver Foundation Web site. Available at: http://www.liverfoundation.org Accessed September 10, 2004.

8. Shiffman MI, Brown Jr. RS, Olthoff KM, et al. Living donor liver transplantation: summary of a conference at The National Institutes of Health. Liver Transpl. 2002;8:174-188.

9. Trotter JF, Wachs M, Everson GT, et al. Adult-to-adult transplantation of the right hepatic lobe from a living donor. N Engl J Med. 2002;346:1074-1082.

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13. Kling K, Lau H, Colombani P. Biliary complications of living related pediatric liver transplant patients. Pediatr Transplantation. 2004;8:178-184.

SUGGESTED READINGBasaran O, Karakayali H, Emiroglu R, et al. Donor safety and quality of life after left hepatic lobe donation in living-donor liver transplantation. Transplant Proc. 2003;35(7):2768-2769.

Beavers KL, Cassara JE, Shreshta R. Practice patterns for long-term follow-up of adult-to-adult right lobectomy donors at US transplantation centers. 2003;9:645-648.

Brown RS Jr. Evaluation of the potential living donor. Transplant Proc. 2003;35:915-916.

Goldstein MJ, Salame E, Kapur S. Analysis of failure in living donor liver transplantation: differential outcomes in children and adults. World J Surg. 2003;27(3):356-364.

Humar A. Donor and recipient outcomes after living donor liver transplantation. Liver Transpl. 2003;9 (suppl 2):42-44.

Rudow DL, Brown RS Jr. Evaluation of living liver donors. Prog Transplant. 2003;13:110-116.

Schwartz M. Candidate selection criteria for living donor liver transplantation. Mt Sinai J Med. 2003;70:171-173.

Walter M, Bronner E, Pascher A, et al. Psychosocial outcome of living donors after living donor liver transplantation: a pilot study. Clin Transplant. 2002;16:339-344.

Winsett RP, Russell C, Grewal HP, et al. Perceptions of the donation process from adult-to-adult living liver donors. Prog Transplant. 2003;13:123-129.