Health-related quality of life after anonymous nondirected living liver donation: A multicenter collaboration.

In the study period, 5.6% (12/215) of LLDs were nondirected at UA, 5.2% (12/231) at UC, and 3.5% (12/344) at USC. Across all three centers, 86 ND-LLDs presented for consideration of anonymous donation, while 36 were approved and completed donation ( Supplemental Figure 1 ). Thirty-eight were excluded for medical or anatomic reasons, eleven for psychosocial reasons, and one who withdrew after approval ( Supplemental Table 1 ). Six approved donors had a history of depression, including four patients with active diagnoses at evaluation which were deemed well-controlled. Of the 36 ND-LLDs that completed donation, 30 completed surveys a median of 1.1 [IQR 0.4–3.2] years from donation, representing a response rate of 83%. Four ND-LLDs from UA, one from USC, and zero from UC could not be contacted via telephone. One donor >10 years post-donation declined to participate for personal reasons. Fifty-percent (n=15) of ND-LLDs donated a left lateral segment, 27% a right lobe, and 23% a left lobe ( Table 1 ). Most ND-LLDs were female (67%) and non-Hispanic White (n=27, 90%). The average age at donation was 38.9±11.2 years. Most ND-LLDs were highly educated (83%) and were married, partnered, or in a long-term relationship (57%). Review of pre-transplant evaluations indicated that most ND-LLDs (n=26, 87%) had definitively engaged in prior altruistic acts, including prior kidney donation (n=11, 37%), blood donation (43%), organ (57%) or bone marrow (30%) donor registration, community volunteerism (37%), or unsuccessful attempts at directed solid organ donation (13%) ( Table 1 ). Many ND-LLDs (n=14, 47%) had careers that were either grounded in altruism or involved service, including education, emergency response, foreign service, healthcare, human resources, law enforcement, or the military. The majority of liver donations were allocated to pediatric recipients with a pre-transplant diagnosis of biliary atresia ( Table 1 ). One-year patient and graft survival for ND-LLD recipients was 90%, with 100% patient and graft survival for pediatric recipients. Among pediatric recipients, all were healthy with functioning grafts and no indication of recurrent liver disease by the time of donor follow-up (median 1.7 [IQR 0.5–3.3] years). Three adult recipients had died by the time of ND-LLD follow-up ( Supplemental Table 2 ). In all, 11 donors (37%) experienced a complication of Clavien-Dindo Grade I or higher with only one major complication (Clavien-Dindo Grade IIIb) ( Table 2 ). This donor experienced hemorrhage on postoperative day 1 which required a blood transfusion and surgical exploration for a small arterial bleed. There was no evidence of long-term medical sequelae in any ND-LLD, whether participating in this study or not, who had a post-operative complication. Of the 20 ND-LLDs visiting a physician since surgery, the majority (n=14, 70%) reported doing so for routine follow up with their primary care provider. Eight ND-LLDs (27%) reported a new medical condition since post-donation ( Table 4 ). Five donors (17%) reported undergoing surgery since donation, none of which were directly relevant to their history of liver donation. A majority of ND-LLDs (73%) reported resuming normal physical activity post-donation ( Table 3 ). ND-LLDs (n=8, 27%) not resuming the same level of physical activity were surveyed less than six months post-donation. The majority of ND-LLDs reported exercising since donation (n=28, 93%), and 63% (n=19) reported their physical strength to be equal to or greater than prior to surgery. Of the ND-LLDs who reported a reduction in physical strength (n=11, 37%), the majority (n=8, 73%) were surveyed within one year of undergoing donation. The majority of ND-LLDs reported feeling positive or neutral about their surgery (n=28, 93%) ( Table 3 ). One donor reported conflicted feelings initially due to surgery-related complications but ultimately felt reassured of their decision as “everything worked out in the end”. The remaining donor did not elaborate. Regarding ND-LLD perception of overall health since surgery, 100% expressed either a positive or neutral outlook. All but two ND-LLDs reported that surgery had a positive or neutral impact on them emotionally (n=28, 93%). Many indicated that they experienced newfound gratitude for their good health, found it easier to empathize with others, or became an advocate for living organ donation. Two ND-LLDs reported conflicted feelings regarding the emotional impact of donation: one attributed the feelings to a painful recovery and the second indicated that their perspective on life changed after experiencing surgery-related post-traumatic stress. No ND-LLD regretted their overall decision to donate. A majority of ND-LLDs (n=17, 57%) reported surgery-related discomfort to be less than or similar to pre-operative expectations ( Table 3 ). Of the 11 ND-LLDs who had donated a kidney in the past, five (45%) reported discomfort to be greater than initially expected. Many donors reported feeling positive about their surgical scar (n=11, 37%) or neutral due to indifference (n=15, 50%). Three donors (10%) felt negatively about their surgical scar. Two donors reported feelings of self-awareness during abdominal exposure in public areas, while the third did not elaborate. One donor did not respond. The majority of ND-LLDs felt that their transplant team provided them with adequate education (n=21, 70%). Nine ND-LLDs (30%) felt they could have been provided with more information and offered suggestions for improvement ( Table 5 ). There was consensus that informed consent and donor wellbeing were a high priority. ND-LLDs shared common motivations to donate. Representative quotes from detailed survey answers are displayed in Table 6 . We caution against interpreting these motivations as the sole justification used by the transplant team before approving a candidate for donation. Many reported positive experiences with past kidney donation and a desire to extend their altruism through liver donation. Some had undergone evaluation for directed liver donation only for their intended recipient to die prior to transplant or no longer remain eligible, motivating them to inquire about ND-LLD. Others felt motivated by a personal connection to organ donation from the experience of an unmatched loved one in past or present awaiting transplant. Although most ND-LLDs viewed anonymity positively in that it preserved their altruistic act, many donors were willing to set it aside if it could motivate others to donate. Most donors felt comfortable with breaking donor: recipient anonymity insofar as their recipient was agreeable. Some noted interacting with their recipient on a regular basis via letters or phone calls; others noted that a future date had been set. Prior to donation, all but one donor was either in school or employed (97%) ( Table 7 ). Two donors, <3 months post-donation, were still on leave from employment, with scheduled returns within two weeks of survey completion. Only 11% (n=3) of respondents reported transient difficulties upon initial return to work, attributed to fatigue. No ND-LLD reported that living donation affected their ability to find employment. All ND-LLDs (n=30, 100%) reported that donation did not impact their health insurance status ( Table 7 ). One donor was uninsured at the time of survey and was waiting for the next enrollment period to obtain health coverage. With regards to life insurance, four ND-LLDs attempted to purchase coverage after surgery, and three (75%) did not report difficulty doing so. One ND-LLD was denied life insurance coverage due to applying <5 years after undergoing major surgery. One donor who purchased life-insurance prior to surgery had maintained coverage. To assess long-term HR-QOL outcomes, ND-LLD SF-36 results were compared to U.S. population norms ( 29 ). Briefly, PCS c is a summary measure that aggregates physical functioning, role-physical, bodily pain, and general health scale scores of the SF-36, whereas MCS c aggregates vitality, social functioning, role-emotional, and mental health scale scores ( 29 ). Comparatively, ND-LLDs experience similar outcomes, with no difference in mean scores for most individual SF-36 scales as well as aggregate PCS c , and MCS c summary measures ( Figure 1 ). There were no differences in PCS c ( P =0.10) and MCS c ( P =0.14) for each type of donation (LLS, left, or right lobe) ( Supplemental Figure 4 ). No differences in SF-36 outcomes were observed in ND-LLDs donating to adult recipients who had died by the time of donor follow-up (n=3) (data not shown).

This study represents the first examination of HR-QOL in 30 ND-LLDs followed for a median of 1.1 years post-donation at three North American LDLT centers. The overall ND-LLD survey response rate was high (83%). Demographically, ND-LLDs in this sample were similar to U.S. registry data ( 13 ). The majority of donor grafts were allocated to pediatric recipients, all of whom remain alive with no evidence of recurrent liver disease. In all, ND-LLDs experienced a 37% complication rate, with only one Clavien-Dindo IIIb, comparable to the overall morbidity of 40% for LLDs from the A2ALL experience ( 33 ). None of the ND-LLDs, whether participating in this study or not, have been documented to experience long-term sequelae related to donation. Between our three centers, the first anonymous nondirected living liver donation was performed in 2000. This case was also first to be documented in the U.S., occurring prior to published reports in North America and Europe ( 8 – 10 ). There were no guidelines at the time to establish best practices for evaluating these donors, nor recommendations regarding allocation. Ultimately, a decision to accept the first ND-LLD was made, guided by principles similar to those reported by Toronto in 2007 ( 9 , 11 , 12 ). Briefly, these included 1) expectation of excellent medical outcomes associated with the procedure for both donors and recipients, 2) respect for donor autonomy, 3) potential for psychological benefit for the donor, and 4) a chance to expand the organ pool for transplant candidates with no living donor options. Eligibility criteria for accepting ND-LLDs were similar across our centers. In this regard, motivations and mental health of individuals volunteering as ND-LLDs are an important consideration. A recent study assessing long-term donor mortality in >10,000 live liver donors in Korea found suicide, while extremely rare, to be the most common cause of donor death ( 38 ). With the understanding that ND-LLDs as a group are motivated by factors intrinsically difficult to define, these findings underscore a critical need for transplant teams to identify those at risk for post-donation psychiatric morbidity. In our study sample, four patients had an active diagnosis of depression, which was assessed and determined to be well-controlled with medication at the time of donation. All patients with psychiatric histories were followed closely by their primary care providers after surgery. None of these individuals reported worsening of baseline symptoms post-donation. Most survey respondents had a history of altruistic acts. Eleven (37%) had previously donated a kidney, which is consistent with 29% of ND-LLDs with prior kidney donation in U.S. registry data ( 13 ). There is debate regarding the ethical justification of utilizing this distinct donor group ( 12 ). Although we did not observe differences in HR-QOL outcomes in patients with prior kidney donation, 45% reported greater post-operative discomfort than initially expected. This may be in comparison with their kidney donation experience and should be highlighted in pre-transplant counseling of this population. Continued long-term follow-up is required to accurately assess the risks of living liver donation in the subgroup of patients with a history of kidney donation. Allocation of ND-LLDs is not standardized and has many considerations ( 13 ). OPTN guidelines indicate that living nondirected donor organs be allocated to the first transplant candidate on the waiting list following the same standardized policies of nondiscrimination utilized for allocation of deceased donor organs ( 39 ). The collective experience of our three transplant centers has been to preferentially allocate ND-LLD allografts to children, secondary to the perception of less donor operative risk for left lateral segment donation when compared to right lobe liver resections and the observation that children are disadvantaged in the current allocation scheme ( 40 , 41 ). That being said, we continue to face the challenge of how, and if, donors can play a role in the allocation process without compromising on equity and justice for all stakeholders involved. Although there is no best accepted practice for allocating ND-LLD allografts, we believe that continued reporting of transplant center practices is critical for development of policy that balances the altruism and well-being of ND-LLDs with the needs of transplant candidates ( 42 ). Return to baseline physical health is an important consideration for LLD candidates. Optimizing informed consent requires disclosure of comprehensible information in this regard, considering that LLDs can experience greater morbidity than initially expected ( 43 ). In a recent longitudinal study involving self-reported outcomes in 220 directed living liver donors, 23% mentioned a decrease in physical activity ( 18 ). Concerns related to difficult recovery, fatigue, nutrition and weight changes, and financial preparation were also endorsed. These are similar to concerns reflected by ND-LLDs participating in this study through suggestions to improve the donation process. Although overall feedback from survey respondents indicated that they felt well-informed, all LLD candidates and ND-LLDs in particular should continue to not only be apprised of such concerns, but also convincingly demonstrate an understanding during informed consent. Financial considerations may play an important role in the future of ND-LLD ( 13 ). Living donors often incur out-of-pocket expenses, related to indirect costs including transportation, childcare, or lost wages ( 44 ). Our data indicate that anonymous donation does not affect employment post-donation. The impact of anonymous donation on financial well-being in our highly educated and employed population of ND-LLDs may not be representative. Thus far, no center in this study has ruled out a willing ND-LLD for financial reasons. Achieving financial neutrality for living organ donors, regardless of relationship (or lack thereof) to the recipient, is critical as LDLT is expanded ( 45 ). Our study reveals that ND-LLDs experience similar outcomes when compared to the general U.S. population across all categories of the SF-36. These findings are in line with both A2ALL and single-center reports, which have consistently characterized SF-36-measured HR-QOL in LLDs as similar, if not better, than U.S. norms ( 16 , 17 , 20 ). With these findings and 1.1 years of median follow-up, we cannot establish direct psychological benefit derived from anonymous donation for ND-LLDs specifically, as has been previously hypothesized ( 11 ). Nevertheless, our analysis of SF-36 responses from a population of primarily left lateral segment ND-LLDs indicates that HR-QOL post-donation remains well preserved. This cross-sectional study has several strengths. It is the first to report psychosocial outcomes in ND-LLDs using HR-QOL survey tools, including the validated SF-36. The population includes donors from three North American LDLT centers who are demographically similar to the profile of ND-LLDs in national reports, which may increase the generalizability of results. Although an 83% response rate is high for a study of this design, six ND-LLDs lost to follow-up cannot be ignored. It is reassuring that U.S. ND-LLDs lost to follow-up (n=2) would be noted in U.S. registry data had they experienced catastrophic outcomes post-donation ( 13 ). The present status of Canadian ND-LLDs lost to follow-up >1 year post-donation (n=4) remains to be confirmed. Our study presents several limitations. A small sample size precludes ND-LLD subgroup analysis. Also, although the USC DQLS was developed in a structured manner by LLD professionals, it has not been validated using principle components analysis ( 46 ). The USC DQLS also does not explicitly query ND-LLDs for symptoms such as incisional pain, gastrointestinal side effects, and depression which have been previously reported in the LLD literature, instead relying on self-reported outcomes. This introduces the possibility of 1) recall bias, particularly for ND-LLDs followed many years after donation, and 2) implicit bias resulting from a telephone survey conducted by a physician, which may have led to underreporting of negative symptoms. This study is also limited by a relatively short duration of follow-up. As such, risk of de novo liver disease in the remnant liver of ND-LLDs was not apparent. Nevertheless, patients with a prior partial hepatectomy should still be candidates for partial nonanatomic liver resection or other ablative therapy if required. To limit unexpected hardship and maximize informed consent, future ND-LLDs should be counseled with regards to potential impact on management of unexpected future medical diagnoses. Our assessment of a unique cohort of ND-LLDs reveals that morbidity, comparable to directed donor counterparts, was well tolerated and accepted. Overall satisfaction was high, and no donor reported any regrets upon follow-up. Both donor and recipient medical outcomes were excellent, with ND-LLDs experiencing positive financial, psychosocial, and HR-QOL outcomes well after surgery. Thus, in a selected cohort of ND-LLDs, there does not appear to be any clear contraindication to anonymous partial liver donation. Despite good HR-QOL outcomes, our findings indicate that recipients of ND-LLD grafts may derive more benefit from than ND-LLDs themselves. Therefore, continued long-term follow-up of this donor group on a prospective, multicenter basis is required. Guidelines establishing best practices for anonymous donor graft allocation, along with the donors’ role in the allocation process, remain topics of future investigation.

Institutional Review Board authorization was obtained for each center: HS-16-00876 (USC), 19-072 (UC) and 00086036 (UA). All ND-LLDs who had donated between 6/2000–6/2019 at USC (n=12), UC (n=12), or UA (n=12) were approached between 6/2019–1/2020 to participate in this study ( Supplemental Figure 1 ). No donor hepatectomy was performed laparoscopically. Based on registry data, USC and UC are in the top three American centers and UA is second to the Toronto group for Canadian experience with ND-LLD ( 25 , 26 ). Each institution offers LDLT at separate pediatric and adult LT programs with the same surgical team. Demographic data and post-operative complications occurring up until the date of survey were retrospectively reviewed for ND-LLDs at each center ( 27 ). The following data were collected: age at donation, race/ethnicity, BMI, education level, marital status, children, documentation of prior altruistic acts, type of liver donation, and length of initial hospital stay. For recipients of ND-LLD grafts, data on pre-transplant diagnoses, age at transplant, and post-transplant outcomes were also collected. ND-LLDs were contacted by physician members of the research team via telephone to complete two surveys: the RAND version of the SF-36 and the USC DQLS ( 28 ). ND-LLD SF-36 results were compared to the most recently available U.S. population norms ( 29 ). At all centers, the same donor team evaluates ND-LLD candidates for both adult and pediatric recipients. Potential donors undergo an independent assessment by an internist physician, transplant surgeon, psychosocial assessment by a social worker, and selective independent psychiatric assessment when deemed necessary. Per national regulatory board requirements, all donors are assigned an independent living donor advocate, who is a social worker designated to advocate for and promote donor autonomy, protect voluntariness, and assist communication and understanding of the consent process. Potential donors are informed of their option to withdraw at any time in the process leading up to donation. Potential ND-LLD candidates do not qualify for donation if they are unsuitable secondary to medical or psychosocial risk ( Supplemental Table 1 ). During psychosocial evaluation, donors are screened for their capacity to give informed consent, emotional and mental health, financial status, and social support system. Additional attention, in comparison to directed donor evaluation, is focused on motivation, prior history of altruistic behavior in keeping with consistent motivation, as well as willingness to maintain anonymity. At UC, all donors are assessed for psychosocial risk using tools such as the Psychosocial Assessment of Candidates for Transplantation (PACT) ( 30 ) and Personality Assessment Inventory (PAI) (beginning 2018) which provides indices of psychopathology and personality disorders ( 31 , 32 ). ND-LLDs with a history of psychiatric conditions must be deemed low risk for complications post-donation prior to approval. All candidates are informed of the risks posed by living liver donation per OPTN guidelines, focusing on comparatively higher risk of surgical morbidity and mortality as well as longer recovery time when compared to kidney donation ( 33 , 34 ). SRTR data on survival outcomes is provided, and the patients’ spouse, family or support system is engaged in these conversations. There are no standardized protocols for allocating ND-LLD grafts ( 13 ). Generally, once a donor is approved for donation, grafts are preferentially allocated to pediatric recipients by blood group, waitlist-priority, anatomic compatibility, and technical complexity. If no appropriate pediatric candidate is available then the graft is offered to an adult by the same allocation schema. All centers are willing to consider right hepatectomy donation if anatomically appropriate for the donor. Once pairing for transplantation has occurred, donors, recipients, and medical personnel are notified of the anonymous donation. Both donors and recipients are counselled on the importance of maintaining anonymity to protect both parties. The day of the operation, donors and recipients check into separate physical locations, are kept in separate pre-operative holding areas, and patient identifiers are not made visible outside of patient rooms. At least six weeks are allowed to pass post-procedure for recovery. After that time, if a donor or recipient wish to communicate, the independent living donor advocate facilitates the process. The USC DQLS was designed in 2004 as an LLD-specific assessment tool by USC’s transplant team with a biostatistician and consists of 44 questions assessing donor-reported outcomes across five categories: medical condition, physical activity, employment, insurance, and emotional status ( Supplemental Figure 2 ). Assessment of HR-QOL for directed LLDs at USC has been previously published using this instrument, and a response coding system was developed using well-established qualitative techniques ( 20 , 35 ). Verbal responses for open-ended questions were recorded as written notes (reflexive method) by one physician at each center, and notes were read back to be approved by the donor as accurate. Exemplary quotes were noted verbatim. Data were thematically coded by a trained member of the research team (M.R.). The SF-36 is a standardized tool assessing generic health outcomes which can be compared to broad population datasets using well-established techniques ( 28 , 29 , 36 , 37 ). The survey consists of 36 itemized questions that cluster into eight categories, or scales. Standardized and correlated physical (PCS c ) and mental (MCS c ) component summary scores for individual respondents can be calculated by assigning country-specific weights to the eight SF-36 scales ( 36 , 37 ). Mean standard normal scores for each scale, along with orthogonal PCS c and MCS c , were compared to the most recently available U.S. population norm from 1998, in line with other LLD studies ( 16 , 29 ). Mean and standard deviation (SD) are reported for continuous variables, and frequencies and percentages are reported for categorical variables. For the SF-36, mean standard normal scores for each scale are reported. A two-sided one sample t-test with equivalence margin of one standard deviation from the norm was used for comparison of orthogonal PCS c and MCS c between ND-LLD and general U.S. populations. All analysis was performed using SAS v9.4, and figures were generated using Excel v16.30.

The shortage of deceased donors combined with cultural barriers to deceased organ donation in many countries has resulted in the expansion of living donor liver transplantation (LDLT) ( 1 , 2 ). LDLT results in equivalent or even superior outcomes for graft and recipient survival when compared to deceased donor liver transplantation, particularly among pediatric patients ( 3 – 7 ). However, many patients lack access to a suitable living donor. To expand the availability of LDLT, several centers have reported their utilization of a novel subset of living liver donors (LLDs) known as anonymous (sometimes referred to as ‘altruistic’ or ‘good Samaritan’) living liver donors ( 8 – 13 ). These donors represent a highly motivated group of individuals who volunteer to anonymously donate a portion of their liver to either 1) a biologically unrelated but specific recipient in need (‘anonymous directed’) or 2) anyone in need on the list (‘anonymous nondirected’ or ‘ND-LLD’). Since the first case performed in 2000, 105 ND-LLDs have been reported in the U.S., with 39 in 2019 alone ( 13 ). Directed living liver donors, who share a biological or close social relationship with their recipient, maintain excellent health-related quality of life (HR-QOL) even up to 20 years post-donation ( 14 – 20 ) and rarely regret their decision to donate ( 14 , 17 , 21 ). Meanwhile, literature on ND-LLDs is sparse. The role of nondirected donors was first explored in kidney literature ( 8 – 10 , 22 – 24 ). While directed donors may feel pressure to donate, it is argued that the nondirected donor may be the only donor that is truly autonomous and free of any potential coercion. There is ongoing debate on how to balance concerns related to nondirected donor motivation and informed consent with ethical considerations and liability risk for transplant centers ( 13 ). Recently, the Toronto program published a comprehensive report of their experience with 50 anonymous LLDs, suggesting that these donors can reduce the gap between organ demand and availability with appropriate clinical expertise ( 12 ). As more programs consider ND-LLDs, questions regarding motivation, psychosocial well-being, and HR-QOL post-donation in this donor population remain ( 13 ). To better understand the practice of consideration of ND-LLDs and their experience, we established a multi-center collaboration between the University of Southern California (USC), the University of Colorado (UC), and the University of Alberta (UA). The objectives of our collaboration were to examine HR-QOL and the overall impact of LDLT on medical, physical, emotional, employment, and insurability outcomes in this distinct donor group.