What Are the Risks to Donors in Living Liver Transplantation?

From Medscape Gastroenterology > Ask the Experts

William F. Balistreri, MD

This question may have been prompted by the recent publicity[1] about the death of a man in Colorado after donating part of his liver to his brother. Subsequently, all live donor liver transplants were temporarily suspended at that hospital.
If the death is ultimately attributed to the procedure it would be the fourth such death in the United States, according to the United Network of Organ Sharing (UNOS) and the second such death this year. This comes at a time when living liver donation has fallen to less than 50% of the number of live donations performed at the peak in 2001, currently accounting for approximately 3% of all adult liver transplants in the United States.[2,3]

Live donor liver transplantation, specifically, performance of a major hepatectomy on a healthy individual who has no medical indication other than offering an allograft liver for the recipient, has long been viewed with caution and skepticism.[4] Therefore, substantial efforts are expended to ensure the safety and long-term well being of the donor. The best outcomes for both donors and recipients have been maximized via technical refinements, innovative pre- and postoperative management strategies, and careful follow-up.

Why are living donors needed? The number of patients awaiting liver transplantation in the United States (approximately 15,000) greatly exceeds the supply of cadaver donor organs (approximately 4500/year), according to the UNOS registry. Thus the waiting time for liver transplantation and death on the waiting list have increased in recent years. This growing disparity between the demand for liver transplant and the supply of deceased donor organs was the stimulus for the development of living donor liver transplantation. Initial success with transplantation of live donor liver segments into children and the use of cadaver donor split-liver transplantation evolved into adult-to-adult living donor liver transplantation (A2ALL) using the right portion of the liver.[5] The multicenter A2ALL consortium has provided evidence that adult living donor liver transplantation is a viable option for liver replacement and approximately 300 A2ALL procedures have been performed in the United States.[6]

Living donor liver transplantation has several advantages over cadaver donor transplantation, including transplantation in a scheduled, elective, and timely fashion, permitting areduction in waiting time and waiting list morbidity and mortality.[4] In addition, donors may derive a psychological benefit from the fact that they were able to help the recipients; the donors express a sense of deep satisfaction from giving a loved one their "gift of life."[7]Nevertheless,every effort is made to ensure that donors who choose to proceed are free from coercion. The transplant team provides recipients, potential donors, and families with counseling and support through every phase of the process. A donor advocate, independent from the team, is available to ensure that the donor understands the issues involved with donation and excludes donors who have issues related to personal life, work, or finances that would be affected by their serving as a donor. Potential living donors then undergo an extensive evaluation to ensure that they are in optimal medical condition to proceed with organ donation. Medical evaluation also carries risks.[8,9]

Following living donor liver transplantation, the donor's liver regenerates to full size within a few weeks, without long-term impairment of liver function. Most donors are hospitalized briefly (about 1 week after the donation) and recover completely. However, as illustrated by the Colorado case, this procedure is not without risks. The estimated risk of mortality is 0.5 to 1%. Overall donor morbidity is high, estimated to be roughly 35%.[10] This is usually related to the surgical incision and the possibility of blood clots; other reported problems include bleeding, infection, bile leaks, damage to the bile tree, or risks from anesthesia. Donors have reported chronic problems, including bile strictures, reoperations, and chronic pain.

The most common postoperative complications among donors for living donor liver transplant involve the biliary tract; the incidence of biliary complications in donors is approximately 5%.[11] Most of the biliary complications can be treated by nonsurgical methods or interventional procedures. Guba and colleagues performed a single-center, retrospective review of all patients brought to the operating room for donor hepatectomy.[12] Of 257 right lobe donors, the donor operation was aborted in 5% primarily because of aberrant biliary ductal or vascular anatomy or unsuitable liver quality.

In rare cases, if the remaining liver is damaged, the donor may also need a liver transplant. Organ Procurement and Transplant Network data reveal that 5 of 3632 (0.1%) living liver donors were subsequently listed for liver transplant.[13] One living donor died after being placed on the waiting list, 3 candidates received deceased donor liver transplants within 4 days after listing, and one candidate was removed from the waiting list following improved health.

In several recent case series, the rate of complications in living liver donors has been tracked. The Clavien 5-tier grading system was applied retrospectively by Marsh and colleagues to determine the incidence of potentially (grade 3), actually (grade 4), or ultimately fatal (grade 5) complications during the first post-transplant year.[14] All 121 donors survived; however, 13 donors (11%) had grade 3 (n = 9) or IV (n = 4) complications.Adcock and associates analyzed the outcomes of the first 202 consecutive donors performed at their center.[15] Donor survival was 100%; however, 40% of the donors experienced a medical complication during the first year after surgery (21 grade 1, 27 grade 2, 32 grade 3). All donors returned to predonation employment or studies, although 4 donors (2%) experienced a psychiatric complication. Fernandes and colleagues analyzed the outcomes of live liver donors in a single Brazilian center.[16] None of the 74 donors experienced life-threatening complications or died; however, 28 complications were observed in 26 patients: grade 1 (n = 11; 40%); grade 2 (n = 8; 29%); and grade 3 (n = 9; 32%). No patient presented with grade 4 or 5. In a study of 1262 living donors by Iida and associates, the overall complication rate and the severity were significantly higher in right and extended right lobe graft donors than in other donors (44% vs. 19%, P < 0.05).[17] Donor age and prolonged operation time were also found in multivariate analyses to be independent risk factors for complications.

In summary, the risk of dying from living liver donor surgery may be as high as 0.5% when donating the right lobe. If all complications are included, 1 of every 3 donors will experience a complication; most are considered minor or have no permanent sequelae.[18] Thus, centers must carefully weigh the risks against the benefits. Likewise, potential living liver donors should balance the decision to donate with the advice of family, friends, an independent donor advocate, and the medical/surgical team. As stated by Marsh and colleagues, "no matter how carefully right lobar living donor transplantation is applied, the historical verdict on the ethics of this procedure may be harsh."[14]

Cadaver donor organ availability appears to have reached a plateau despite initiatives directed at increasing organ donation.
If enough cadaver organs could be obtained to meet the needs for liver transplantation, living donor liver transplants would not be necessary. Thus, we all need to expand our efforts to increase donor awareness and promote registration.