Living donor liver transplantation (LDLT) was first successfully performed in 1989. The procedure was developed in response to a shortage of acceptable organs for transplantation and was initially employed to provide partial grafts (usually left lateral segments) to pediatric recipients facing a high likelihood of dying while waiting for a deceased donor graft meeting the stringent size parameters required.1 Success in this arena was followed by the expansion of the technique to include adult recipients and larger grafts, including entire right lobes and extended right lobes. Patients with end-stage liver disease who have living donors are able to undergo transplantation more quickly, and this has led to patient and graft survival rates similar to (or in some cases superior to) those achieved with deceased donor liver allografts.2-6
The benefit of LDLT to the recipient is obvious. The benefit to the donor, though real in many instances, must be weighed against the equally real possibility that harm may accompany donor hepatectomy. As illustrated by the recent deaths of right hepatic lobe donors in the United States, the potential for a catastrophic outcome, though small, is not an abstraction.3 Approximately 35% to 40% of right hepatic lobe donors will experience an adverse event related to the donation, and 10% to 12% of these events will be serious and require intervention.2-4
Currently, there are no widely accepted standards for the evaluation of potential living liver donors, nor are there standards for reporting and reviewing adverse events that occur during the perioperative and recovery periods following actual donation. Programs practicing LDLT must be actively involved in the evaluation of current processes with the aim of identifying factors associated with donor morbidity and devising solutions to mitigate the incidence. It is impossible to completely eliminate risk for donors. In this article, we review some of the factors associated with increased donor safety.
EXPERIENCE OF THE PROGRAM
LDLT is an extremely complex undertaking, and success requires a multidisciplinary approach. Skilled surgical talent is an obvious requirement, but strong input from hepatologists, anesthesiologists, blood bank staff, radiologists, social workers, pathologists, and nurses is essential. The transplant center must be able to perform complex donor and recipient evaluations in an expeditious manner to allow the selection of compatible pairs. The teams must be able to coordinate 2 surgeries, and the institution must have the facilities to deal with patients recovering from major hepatobiliary surgery. Even when groups possess all these attributes, there is clearly a learning curve of approximately 20 procedures for LDLT.4 Later cases will have better outcomes than earlier ones, even when teams and institutions are used to providing complex care.
It is impossible to overemphasize the critical importance of having a skilled hepatobiliary surgeon responsible for performing the donor hepatectomy. The skills required to perform a living donor right hepatic lobectomy are different from those required to procure and implant a deceased donor liver allograft. This was implicitly recognized by the Organ Procurement and Transplantation Network/United Network for Organ Sharing (the agency charged with accrediting transplant programs in the United States) when it began to require a program to have at least 2 surgeons who had performed at least 20 documented hepatobiliary procedures within the preceding 2 years in order to be designated as an approved LDLT program.3 The end result must be a division of the hepatic parenchymal, vascular, and biliary structures that results in a graft for transplantation and a donor remnant that are life-sustaining for the recipient and the donor and are associated with minimal surgical complications. This is best accomplished by individuals proficient in hepatobiliary and transplant surgery.
LDLT, living donor liver transplantation; MHV, middle hepatic vein.
SELECTION OF DONORS
A comprehensive review of donor-recipient physical matching for LDLT is beyond the scope of this article and has been reported previously,5-7 but the ethical principals that allow LDLT to occur require the transplant to have a reasonable chance of being successful. In general, this means that the recipient must be well enough to survive the surgery and to function with a reduced liver mass until hepatic regeneration occurs. The pair must be ABO-compatible, and the liver must be of adequate size and possess no variant anatomy that precludes the use of a partial graft or leaves the donor with a liver remnant of suboptimal function.
The medical and psychological suitability of donor candidates for progressing to actual donation should be determined by individuals who are independent of the recipient providers. The minimally acceptable donor team should include a surgeon, a physician, a psychiatrist and/or social worker, and a nurse coordinator. There should also be a designated independent donor advocate whose role is to ensure that the donor is educated about the process and is a willing participant.
We and others5, 7 have previously published detailed descriptions of our preferred donor evaluation algorithm. All candidates must undergo a complete physical examination and blood workup, which includes routine hematology and chemistry tests, liver function tests, hepatitis serologies, a lipid profile, and autoimmune markers. Additional testing should be added as indicated for donors with a family history of liver or autoimmune disease. It is important that this portion of the evaluation be thorough. Significant occult diseases, including unsuspected and potentially life-threatening malignancies, have been uncovered during this phase of the evaluation.
PREDONATION LIVER BIOPSY
The performance of liver biopsy during the donor evaluation is controversial, with some groups recommending routine biopsy in all potential donors and others not recommending it.8-10 The advantages are that occult pathologies will likely be identified before the time of donation and that the incidence of aborted hepatectomies with the attendant surgical and anesthetic risks will, therefore, be reduced. The disadvantage is that the positive biopsy yield is low, and there is a risk of complications, including hemorrhaging. We recommend liver biopsy for select donor candidates. Biopsy is recommended for candidates with any abnormalities in liver function tests or autoimmune markers, with imaging studies suggestive of steatosis, with a body mass index > 28 kg/m2, with a genetic relationship to an individual with immune-mediated liver disease, or with a personal history of alcohol or substance abuse. In our experience, this algorithm has allowed 78% of our potential donors to avoid liver biopsy and has not resulted in any unexpected pathologies or aborted hepatectomies at the time of donation. The complete algorithm, which focuses on those at significant risk for hepatic pathologies, has been published.11
DETERMINATION OF THE HEPATIC VOLUME AND ANATOMY
Donor safety is best served if an accurate determination of the hepatic volume and the vascular and biliary anatomy is made before the actual hepatectomy. Modern high-resolution magnetic resonance imaging and computed tomography imaging combined with sophisticated computer-assisted analysis techniques are available that can create 3-dimensional models of the vessels, ducts, and hepatic volume.12, 13 The identification of an aberrant anatomy that would preclude the safe division of a donor's vascular or biliary tree during the early stages of the evaluation would allow the evaluation to be truncated well before surgery and prevent the dangers of an aborted hepatectomy. Precise volume calculations allow informed planning of the surgical procedure before the actual donation. Decisions about which lobe will be used and what (if any) back-table reconstruction or recipient inflow modulation will be needed to optimize adequate graft function can be made ahead of the actual surgery. Any specialized vessels needed for the recipient reconstruction or any necessary equipment (eg, flow monitors) may be obtained in advance. No amount of preparation or imaging can eliminate all unexpected occurrences during donor hepatectomy. However, modern imaging and volumetric analysis have greatly reduced the incidence of the intraoperative discovery of anatomic variants that render grafts suboptimal or unusable. As such, they should be employed in LDLT donor evaluations whenever possible (Fig. 1).
EXTENT OF DONOR HEPATECTOMY
The unique regenerative capacity of the liver allows up to 70% of the original liver volume to be removed without irreparable damage being caused.14 In the past, this characteristic, along with data indicating that recipients of larger volume grafts enjoy better clinical outcomes than recipients of smaller grafts, may have influenced LDLT teams to procure larger grafts whenever possible. However, the amount of hepatic parenchyma remaining in the donor after hepatectomy has been repeatedly identified as the single most important predictive factor for donor outcomes. Individuals with larger remnant volumes consistently have fewer adverse events, shorter lengths of stay, and faster returns to predonation activity levels.15-20 Many of the studies had low patient numbers, and there was no matching by donor age or predonation physical condition, but their findings were consistent in that donors with lower residual liver volumes experienced more problems.
The Toronto group recently published a comprehensive review of its experience with different types of donor hepatectomies.15 This well-controlled study compared 45 consecutive patients who underwent left hepatectomy [left hepatectomy (4) and left lateral segmentectomy (41)] with matched controls who underwent right or extended right hepatectomy. The overall complication rates were similar (31%-37%), but the incidence of Clavien grade 3 complications was significantly higher in the right hepatectomy (13.3%) and extended right hepatectomy groups (15.6%) versus the left hepatectomy/left lateral segment group (2.2%, P = 0.005). Additionally, they demonstrated significant associations between the remnant volume, hepatic dysfunction, grade 3 complications, and longer hospital stays. Together, these reports provide convincing evidence that multiple measures of donor safety improve when less liver volume is removed for transplantation, and they suggest that henceforth the goal should be to minimize the liver volume removed from the donor.
An additional area of donor hepatectomy that must be discussed is the disposition of the middle hepatic vein (MHV). There is no consensus about whether it should remain with the donor or be included in the graft, although in a recent survey, only 11.8% of LDLT programs worldwide reported the routine inclusion of the MHV in the graft (personal communication). Proponents of leaving the MHV with the donor remnant argue that it increases the margin of donor safety. Those who favor including the MHV with the graft cite the frequent occurrence of venous congestion in segments 5 and 8 in grafts lacking the MHV, and they believe that this lack contributes to an increased incidence of graft dysfunction and impaired regeneration. To compensate for this, programs that do not include the MHV with the graft will often reconstruct significant hepatic veins found in segment 5 and/or segment 8 with autogenous or cryopreserved vein grafts or synthetic conduits.6 Several studies have suggested that the MHV can be included in the graft without increased donor morbidity and may decrease operative times.21-23 Of particular interest is the development of a patient-centered algorithm for deciding whether the MHV should stay with the donor or go with the graft. It is based on the particular hepatic vein (right, left, middle, or inferior) dominant in the total liver volume and the graft weight to body weight ratio in the donor remnant.23 Although these reports are from experienced centers, they represent individual programmatic efforts, and it is not yet clear whether donor safety margins will be maintained if the MHV is routinely included in the graft at less experienced centers.
The majority of individuals who volunteer to be living liver donors are genetically or emotionally related to the potential recipients and become involved in the process in hopes of extending the recipients' lives. They tend to be in better physical and emotional health than their contemporaries and express satisfaction and no regrets with their decision to donate, and most indicate that they would do so again if possible.24-26 However, a minority of donors suffer psychological disorders ranging from mild ambivalence or anxiety to suicidal ideation and completed suicide.27-29 The estimates of affected donors range from 1%-2% to 40% or higher. This variation makes it very difficult to discern an actual rate of psychiatric abnormalities and equally difficult to develop a rational plan for identifying affected individuals and subsequently providing effective treatment for those in need. The problem is multifactorial, but a major contributor is the lack of standardized criteria for gauging when the normal and expected anxiety associated with impending major surgery against the background of a loved one with a life-threatening illness crosses the line and becomes a psychiatric condition of concern. Another variable is the degree to which the psychosocial evaluation influences the outcome of a donor's candidacy. Some programs will eliminate a potential donor with a negative psychiatric report, whereas others consider it in the context of the entire evaluation.24-28 Because of the small but real potential for suicide,29 LDLT programs must develop ways of identifying patients at risk before subjecting them to the stress of donor hepatectomy and the uncertainty of recipient outcomes.
The most commonly reported complications following donor hepatectomy are bile leaks from the cut surface of the liver, wound infections, incisional hernias, and unplanned surgical re-explorations.2, 5, 7, 30 Among these, the most serious are unplanned re-explorations. These usually occur because of hemorrhaging or potentially life-threatening complications such as portal vein thrombosis. The incidence of serious complications, which are defined as events requiring intervention, is 10% to 12%, and the incidence of overall complications is 35% to 40%. It is difficult to assign a cause or devise specific interventions that would reduce these events. Strict adherence to established patient safety protocols must be maintained, but it is unlikely that the aforementioned types of events can be totally eliminated. Information about the incidence of these events must be updated frequently and incorporated into the information provided to potential donors during the education and consent process.
The donation-related death of a living liver donor is a tragedy of indescribable proportions. It is beyond the scope of this article to describe the enormous devastation experienced by the family. It is, however, important to remember that the event wreaks havoc on the transplant team as well. It is, therefore, imperative for LDLT programs to develop a well-considered plan for dealing with all aspects of a donor's death or a catastrophic event. The events surrounding the death must be subjected to an in-depth analysis in close temporal proximity to the event so that pertinent details are not lost and potential causative factors can be identified and corrected. Ratnera and Sandovala et al.31 suggested the establishment of a centralized committee under the auspices of the Organ Procurement and Transplantation Network/United Network for Organ Sharing to review donor deaths in an impartial fashion and to be responsible for the dissemination of pertinent safety lessons learned to other programs. This type of mechanism would in theory have prevented a repetition of the events associated with the continued use of vascular clips implicated in the deaths of kidney donors even after a warning was issued by the manufacturer. Donor safety must be the first priority of all LDLT programs; however, it is unrealistic to assume that the risk of mortality can be completely eliminated from any surgical procedure. Donor candidates must be informed that death is possible, although it is unlikely. The current best estimate is that living liver donors face a mortality risk of approximately 0.5%.
Currently in the United States, there is mandatory follow-up for living liver donors at 6 months and 1 and 2 years. The amount of required information is minimal, and it provides no meaningful insight into the overall well-being of donors. Information obtained during the first phase of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study suggests that there might be long-term negative effects of donation for some individuals.29, 32 Donors must be encouraged to maintain long-term contact with the transplant center, and the center must ensure that the donor is free from adverse donation-related effects or, if such effects are present, is receiving adequate treatment.
LDLT is among the most complex procedures currently performed in medical practice. This high-risk, high-reward endeavor has the potential to restore the recipient to health and to provide the donor with the satisfaction of knowing that his or her willingness to accept some risk has resulted in the saving of the life of another person. The medical professionals involved in LDLT must ensure that the procedure is conducted in a way minimizing the risk to the donor. LDLT has been performed in sufficient numbers to allow the development of experience-based recommendations. We hope that the transplant community will work toward the implementation of this goal in the near future.