Current status and challenges of living donor liver transplantation in the United States

Abstract

KEY POINTS

• Living donor liver transplantation (LDLT) offers greater access to transplantation, reduced waitlist mortality, and superior long-term outcomes compared to deceased donor liver transplantation (LT).

• Barriers to broader adoption of LDLT include a lack of technical experience at transplantation centers, trepidation about possible long-term ramifications of donor steatosis, and recipient and donor reluctance.

• Increasing awareness of LDLT, particularly in minority populations, and alleviating donor-related financial barriers are important means of overcoming the challenges associated with its expansion.

INTRODUCTION

LT is the only life-saving treatment for end-stage liver disease, yet each year almost 1 in 5 patients in the United States dies or becomes too sick while awaiting LT.¹ LDLT emerged in the 1990s as a strategy to address the severe shortage of deceased donor organs and reduce waitlist mortality. Though it offers excellent outcomes, broader utilization of LDLT in the United States remains low.² Barriers to expansion exist on multiple fronts, encompassing donor-related and recipient-related factors, institutional challenges, and lack of public awareness that contribute to an overall reluctance to embrace LDLT’s full potential.^3,4 This review will summarize the growth of LDLT, describe current challenges to broader adoption, and highlight strategies to address these barriers.

GROWTH OF LDLT

LDLT was developed out of split-liver transplantation and introduced to the field of adult LT in the United States in the 1990s. It enjoyed a rise in popularity until 2001, coinciding with the adoption of the Model for End-stage Liver Disease (MELD) score for organ allocation and following a series of highly publicized donor deaths that dampened incipient enthusiasm.⁵ Although rates of LDLT rapidly fell in the early years following these events, LDLT has steadily risen over the last 2 decades.¹ LDLT has consistently been shown to provide shorter waiting times and superior recipient survival than deceased donor liver transplantation.^6,7 Moreover, it offers greater access to LT for patients with lower MELD incorporating sodium (MELD-Na) scores, particularly in females, cholestatic and autoimmune diseases, and cases where the score fails to capture true disease severity. The survival benefit of LDLT has been shown in patients with MELD-Na scores as low as 11.⁸ Yet despite the preponderance of data, LDLT still remains underutilized in the United States, constituting just 5% of all transplantations performed in 2020.¹ Given its advantages, addressing barriers to broader adoption is key to meeting the rising need for LT.

CURRENT CHALLENGES

Institutional factors

While its numbers have risen in recent years, the majority of LDLTs performed remain concentrated among a few transplantation centers.¹ In 2 recent surveys, most participating centers expressed high interest in starting or expanding LDLT but cited the lack of surgical expertise and institutional resources as main barriers.^4,9 Centers adopting LDLT face a steep learning curve, often experiencing more biliary and vascular complications and higher graft failure in the first 20 LDLTs performed before outcomes improve with surgical experience.¹⁰ Moreover, no formalized surgical training for LDLT currently exists. Institutional investment in LDLT would require dedicated financial resources and clinical engagement within the institution. In addition to developing a formalized surgical proctoring program for new LDLT centers to gain proficiency, it is critical to address provider gaps in knowledge about LDLT, recipient and donor candidacy, and appropriate timing of referral at all levels of the institution, from transplant physicians to referring providers. Providing formal LDLT education and publishing accessible resources like the AST Living Liver Donor Provider Tool Kit would help in addressing these knowledge gaps.¹¹

Recipient factors

The culture of unfamiliarity surrounding LDLT also extends to LT candidates. In a national survey, Kaplan et al⁹ showed that recipient unwillingness to consider LDLT and lack of a social network with potential donors constituted major barriers at 31% of LDLT centers. Recipient reluctance has been attributed to lack of LDLT familiarity, concern over donor health risks, uncertainty on how to identify potential donors, and discomfort in asking.⁴ Living donor champion programs, where recipients are paired with an advocate to help them find potential donors, were first established in the field of kidney transplantation and have since been adopted by several LDLT programs.³ Mirroring other such efforts by the National Kidney Registry such as creating a remote donation network or constructing an interactive website with user profiles to match recipient/donor pairs should be considered for LDLT. Implementing these initiatives, developing community outreach efforts, and disseminating lay educational materials to both raise awareness and counter misconceptions are feasible strategies to support recipients and overcome factors contributing to reluctance and misinformation.

Donor factors

Judicious selection of living donors is a critical piece of minimizing donor risk and optimizing recipient outcomes. Insufficient numbers of donor inquiries, existing health comorbidities, and socioeconomic barriers constitute the biggest donor-related barriers to LDLT⁹ (Figure 1). Through a survey many centers indicated that <50% of candidates receive donor inquiries, and of those, more than half are declined for reasons such as obesity or anatomic/blood type incompatibility.⁴ In January 2023, the United Network for Organ Sharing (UNOS) launched the Liver Paired Donation program to allow successful recipient/donor pair matching at different programs across the country; fifteen programs are currently enrolled, with expansion of this pilot program anticipated.

FIGURE 1.

Multistep efforts to increase successful living donation.

In the context of rising rates of obesity, metabolic syndrome, and fatty liver disease that will further limit the suitable donor pool, institutions must prioritize increasing the donor pool by supporting potential candidates through the evaluation process and optimizing their health prior to donation without increasing donor and recipient risk. Culturally concordant donor navigators and dietary or weight loss programs are being increasingly offered by programs. Though some data suggest that high body mass index without metabolic syndrome or significant hepatic steatosis (>10%) does not increase risk of adverse outcomes,¹² in the absence of evidence-based guidelines and data on long-term safety of utilizing steatotic grafts, it remains likely that suitable candidates are declined out of precaution. Prospective studies on safety are needed to guide donor risk assessment. Implementing a registry of all donor candidates—those who successfully donate as well as those declined—to follow short-term and long-term outcomes of both groups would be helpful to inform future risk stratification and decision-making in donor selection. A pilot program called the Living Donor Collective that involved 6 LT programs was completed in 2020 for this purpose. Now in its expansion phase, additional programs are being added with the goal of enrolling all donors and donor candidates in the United States in the future.

Finally, financial concerns tangibly limit participation in living donation. On top of medical expenses, donors incur indirect out-of-pocket costs due to lost wages, travel costs, and childcare expenses, with a substantial number reporting that these costs exceeded their expectations.¹³ Programs like the National Living Donor Assistance Center (NLDAC) exist to help offload this burden but require the donor to meet stringent qualifying criteria, and many are unaware of such aid. More recently, the National Kidney Registry established the Liver Donor Shield, which provides donors reimbursement for up to $2000 weekly for 6 weeks, compensation for travel and lodging, and legal support for wrongful employment termination or insurance discrimination. On a legislative level, the state of New York passed the Donor Support Act in December 2022 that provides reimbursements of up to $10,000 for living donor expenses not covered by insurance. Similarly, the Living Donor Protection Act of 2023 was introduced last April to allow donors to use Family and Medical Leave time to recover from surgery and prohibit insurance companies from upcharging, denying, or limiting life, disability, and long-term insurance to donors. These efforts are responding to the need to make living donation a more financially neutral and thereby accessible option.

LDLT disparities

LDLT expansion requires intentionally focusing efforts and resources on the barriers faced by underserved and vulnerable populations (Figure 2). Individuals of lower socioeconomic status and ethnic minorities like African Americans and Hispanics are under-represented in LDLT, whether this is due to factors such as fewer initial donor inquiries, recipient unfamiliarity with LDLT, higher prevalence of comorbidities, or undue financial burden.¹⁴ Meeting patients earlier in their disease course through outreach programs within their local communities and promoting culturally and linguistically aligned patient navigators would be helpful in promoting education and assisting living donor candidates through the complicated evaluation process, particularly if their primary language is one other than English.¹⁵ Lastly, expansion of financial assistance as discussed to target lower income and minority populations would help alleviate additional barriers to donation.

FIGURE 2.

Framework to help attain equity in liver transplantation. Reprinted with permission from Kaplan A, Wahid N, Rosenblatt R. Ending disparities in liver transplantation: the time to act is now. Am J Gastroenterol. 2022; 117:1181–3. © 2022 The American College of Gastroenterology¹⁵.

CONCLUSION

Although the field of LDLT has continued to grow since its inception almost three decades ago, focused multidisciplinary efforts are required to meet the rising need for transplantation and overcome disparities in LDLT access. Identifying obstacles to LDLT expansion is just the first step in this process. Incorporating changes and evolving our practice to address these barriers on multiple levels will be critical to ensuring the expansion of life-saving therapy to more patients.

CONFLICTS OF INTEREST

The authors have no conflicts to report.