Living donor liver transplantation in the United States: The way forward

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https://onlinelibrary.wiley.com/doi/full/10.1111/ctr.15068?campaign=woletoc

Living donor liver transplantation in the United States: The way forward

Clinical Transplantation Special Issue
Volume37, Issue7
July 2023
Helen S. Te, Abhinav Humar
First published: 03 July 2023 https://doi.org/10.1111/ctr.15068

The success of the first living donor liver transplant (LDLT) performed in a child in Brisbane1 followed shortly by a series of twenty successful pediatric cases in Chicago2 opened the door for LDLT to become a viable alternative to deceased donor liver transplantation (DDLT), not just for children but also for adults. In fact, LDLT has catapulted to become the main mode of liver transplantation in Asia3 and the Middle East,4 where religious beliefs, cultural norms, organ shortage, and political factors have limited the availability of deceased donors. Yet, despite a consistent growth of liver transplantation in the United States (US) over the past four decades, LDLT remains only a small fraction (<10%) of annual liver transplant volumes.5
Living donor liver transplantation has similar or superior graft and patient survival rates when compared to DDLT,6, 7 but widespread adoption of this procedure in the US has remained fraught with many challenges, particularly in the adult population. For this reason, the Living Donor Community of Practice, the Liver and Intestinal Community of Practice, and the Psychosocial and Ethics Community of Practice of the American Society of Transplantation collaborated to hold a consensus conference where national and international leaders in the field gathered to share knowledge and experience. The participants were tasked to identify current barriers that limit the use of this procedure and to formulate effective strategies that will improve access to this life-saving option. The results of the collaborative work and consensus conference are summarized in the six articles included in this special issue.
To set the stage, the first paper “Living donor liver transplantation: A multi-disciplinary collaboration towards growth, consensus, and a change in culture” describes the entire collaborative process, including the administration of a survey of liver transplant centers, an analysis of the transplant registry, and the conduct of the consensus conference. It describes the selection of participants, identifies the domains discussed, and outlines the modified Delphi methodology used in arriving at consensus. At the end of the conference, strategies to overcome the existing barriers were offered, built around a core that rests on the need for a cultural change to one that embraces LDLT.8
To prepare for the consensus conference, a survey was administered to liver transplant professionals to solicit individual attitudes as well as perceived facilitators and barriers of LDLT amongst liver transplant centers in the US. The survey results are reported in the paper, “A survey of transplant providers regarding attitudes, barriers, and facilitators to living donor liver transplantation in the United States.” The majority of respondents recognize that LDLT mitigates organ shortage, but the procedure is infrequently offered as the best first option to patients in need of liver transplantation. Centers without LDLT programs identify the lack of surgical expertise and institutional support as barriers to offering LDLT, while centers with LDLT programs identify recipient and donor selection factors as the obstacles.9
In addition to the survey, an analysis of the Scientific Registry of Transplant Recipients (SRTR) database was performed to determine the influence of recipient characteristics on the selection of LDLT versus DDLT in liver transplant centers that performed both procedures. The findings are outlined in the paper, “Variation in adult living donor liver transplantation in the United States: Identifying opportunities for increased utilization.” On the background of a low overall LDLT rate at 4.4%, practices are widely variable amongst the liver transplant centers, with some centers performing one LDLT only and other centers electing LDLT in 60% of their liver transplants. Some recipient characteristics, such as older age, male sex, and obesity, are noted to be associated with lesser likelihood of LDLT. In addition, racial and ethnic minorities, public health insurance, lower educational achievement, and Northwest and Southeast residence are also associated with less access to LDLT. The authors call attention to the need for further investigation into the social determinants that contribute to disparity in access to LDLT and for further outreach to foster LDLT amongst these populations so as to promote fair access to LDLT.10
During the conference, participants explored barriers encountered in the engagement of institutional stakeholders in LDLT and in the donor and recipient selection process. The discussions are recapped in the paper, “Living donor liver transplant candidate and donor selection and engagement: Meeting report from the living donor liver transplant consensus conference.” Education to counter insufficient awareness and reinforcement of engagement amongst patients, providers, and institutions are advocated. Moreover, future research to fill in data gaps and to standardize donor and candidate selection and additional resources to support the post-donation management of living donors are also recommended.11
Despite technical advances in LDLT that have led to excellent outcomes, at least half of potential living liver donors are still declined for various reasons, mostly medical or technical. In the paper, “Advances and innovations in living donor liver transplant techniques, matching and surgical training: Meeting report from the living donor liver transplant consensus conference,” the authors pinpoint the most pressing medical barriers to LDLT utilization, which included surgical techniques and donor and recipient matching. The development of robust training pathways that provide more exposure to LDLT is projected to increase the number of proficient LDLT surgeons across the country. Furthermore, utilization of emerging data to better guide recipient and donor selection and creation of a formal liver paired exchange program are expected to mitigate donor-recipient mismatches, as has been accomplished in the living donor kidney transplantation community.12
While LDLT undoubtedly benefits the recipient, it subjects the healthy donor to a high-risk procedure that carries a .4% mortality rate and ∼40% complication rate13 with no direct medical gains to the donor. Most donors do derive improved self-esteem, psychological growth, and improved relationships from the donation process, but many also sustain physical issues and financial difficulties.14 In the paper, “Financial, policy, and ethical barriers to the expansion of living donor liver transplant in the United States: Meeting report from the living donor liver transplant consensus conference,” the authors examine the roles of financial strains, regulatory and oversight policies, and ethical controversies in the growth of LDLT in the US. Proposed strategies to overcome the challenges include the expansion of financial resources and public policy changes that promote financial neutrality for donors, optimization of the informed consent process, and further research into long-term physical and mental outcomes of non-directed living liver donors.15
Living donor liver transplantation is a valuable option for patients in need of a liver transplant. However, barriers related to medical, ethical, financial, and psychosocial factors impede its widespread adoption in the US. The papers in this issue specifically address these barriers with workable interventions through education, policy changes, enhanced infrastructure and resources, and research to provide better guidance to center practices. These interventions are crucial for improving access to LDLT and maximizing its potential benefits. Specifically, the LDLT focus needs to shift from “awareness of its existence” to “full acknowledgment and acceptance of its benefit” at multiple levels, including the community, policymakers, healthcare institutions, transplant teams, other medical providers, transplant candidates, and potential donors. In essence, the dictum that needs to be practiced from here onward is, “LDLT is the best option.”8

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https://onlinelibrary.wiley.com/doi/abs/10.1111/ctr.14924?campaign=woletoc

Variation in adult living donor liver transplantation in the United States: Identifying opportunities for increased utilization

Clinical Transplantation Special Issue
Volume37, Issue7
July 2023
Krista L. Lentine, Tomohiro Tanaka, Huiling Xiao, Therese Bittermann, Mary Amanda Dew, Mark A. Schnitzler, Kim M. Olthoff, Jayme E. Locke, Sukru Emre, Heather F. Hunt … See all authors
First published: 02 February 2023 https://doi.org/10.1111/ctr.14924
AnnMarie Liapakis and David A. Axelrod are co-senior authors

Abstract
In the United States, living donor liver transplantation (LDLT) is limited to transplant centers with specific experience. However, the impact of recipient characteristics on procedure selection (LDLT vs. deceased donor liver transplant [DDLT]) within these centers has not been described. Transplant registry data for centers that performed ≥1 LDLT in 2002–2019 were analyzed using hierarchal regression modeling to quantify the impact of patient and center factors on the adjusted odds ratio (aOR) of LDLT (vs DDLT). Among 73,681 adult recipients, only 4% underwent LDLT, varying from <1% to >60% of total liver transplants. After risk adjustment, the likelihood of receiving an LDLT rose by 73% in recent years (aOR 1.73 for 2014-2019 vs. 2002-2007) but remained lower for older adults, men, racial and ethnic minorities, and obese patients. LDLT was less commonly used in patients with hepatocellular carcinoma or alcoholic cirrhosis, and more frequently in those with hepatitis C and with lower severity of illness (Model for End-Stage Liver Disease (MELD) score < 15). Patients with public insurance, lower educational achievement, and residence in the Northwest and Southeast had decreased access. While some differences in access to LDLT reflect clinical factors, further exploration into disparities in LDLT utilization based on center practice and socioeconomic determinants of health is needed.

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https://onlinelibrary.wiley.com/doi/abs/10.1111/ctr.14953?campaign=woletoc

Living donor liver transplantation: A multi-disciplinary collaboration towards growth, consensus, and a change in culture

AnnMarie Liapakis, Michelle T Jesse, Anjana Pillai, Therese Bittermann, Mary Amanda Dew, Sukru Emre, Heather Hunt, Vineeta Kumar, Jayme Locke, Saeed Mohammad … See all authors
First published: 08 March 2023
AnnMarie Liapakis and Michelle T. Jesse are co first authors.
Elizabeth C. Verna and Krista L. Lentine are co-senior authors.

Abstract
Introduction
Living donor liver transplantation (LDLT) reduces liver transplant waitlist mortality and provides excellent long-term outcomes for persons with end stage liver disease. Yet, utilization of LDLT has been limited in the United States (US).
Methods
In October 2021, the American Society of Transplantation held a consensus conference to identify important barriers to broader expansion of LDLT in the US, including data gaps, and make recommendations for impactful and feasible mitigation strategies to overcome these barriers. Domains addressed encompassed the entirety of the LDLT process. Representation from international centers and living donor kidney transplantation were included for their perspective/experience in addition to members across disciplines within the US liver transplantation community. A modified Delphi approach was employed as the consensus methodology.
Results
The predominant theme permeating discussion and polling results centered on culture; the beliefs and behaviors of a group of people perpetuated over time.
Conclusions
Creating a culture of support for LDLT in the US is key for expansion and includes engagement and education of stakeholders across the spectrum of the process of LDLT. A shift from awareness of LDLT to acknowledgement of benefit of LDLT is the primary goal. Propagation of the maxim "LDLT is the best option" is pivotal.

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https://onlinelibrary.wiley.com/doi/abs/10.1111/ctr.14954?campaign=woletoc

Living donor liver transplant candidate and donor selection and engagement: Meeting report from the living donor liver transplant consensus conference

Michelle T. Jesse, Whitney E. Jackson, AnnMarie Liapakis, Swaytha Ganesh, Abhinav Humar, Nicolas Goldaracena, Josh Levitsky, David Mulligan, Elizabeth A. Pomfret … See all authors
First published: 09 March 2023 https://doi.org/10.1111/ctr.14954Citations: 1
Michelle T. Jesse and Whitney E. Jackson are co first authors.
Dianne LaPointe Rudow and Hyosun H. Han are co senior authors.

Abstract
Introduction
Living donor liver transplantation (LDLT) is a promising option for mitigating the deceased donor organ shortage and reducing waitlist mortality. Despite excellent outcomes and data supporting expanding candidate indications for LDLT, broader uptake throughout the United States has yet to occur.
Methods
In response to this, the American Society of Transplantation hosted a virtual consensus conference (October 18–19, 2021), bringing together relevant experts with the aim of identifying barriers to broader implementation and making recommendations regarding strategies to address these barriers. In this report, we summarize the findings relevant to the selection and engagement of both the LDLT candidate and living donor. Utilizing a modified Delphi approach, barrier and strategy statements were developed, refined, and voted on for overall barrier importance and potential impact and feasibility of the strategy to address said barrier.
Results
Barriers identified fell into three general categories: 1) awareness, acceptance, and engagement across patients (potential candidates and donors), providers, and institutions, 2) data gaps and lack of standardization in candidate and donor selection, and 3) data gaps regarding post-living liver donation outcomes and resource needs.
Conclusions
Strategies to address barriers included efforts toward education and engagement across populations, rigorous and collaborative research, and institutional commitment and resources.

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https://onlinelibrary.wiley.com/doi/full/10.1111/ctr.14955?campaign=woletoc

Financial, policy, and ethical barriers to the expansion of living donor liver transplant: Meeting report from a living donor liver transplant consensus conference

Anjana Pillai, Elizabeth C. Verna, Neehar D. Parikh, Matthew Cooper, Carrie Thiessen, Julie Heimbach, Elisa J. Gordon, Gonzalo Sapisochin, Nazia Selzner, Amit Mathur, Emily R. Perito … See all authors
First published: 07 March 2023 https://doi.org/10.1111/ctr.14955Citations: 1
Anjana Pillai and Elizabeth C. Verna contributed equally to this study and share co-first authorship.

Abstract
Introduction
In October 2021, the American Society of Transplantation (AST) hosted a virtual consensus conference aimed at identifying and addressing barriers to the broader, safe expansion of living donor liver transplantation (LDLT) throughout the United States (US).
Methods
A multidisciplinary group of LDLT experts convened to address issues related to financial implications on the donor, transplant center crisis management, regulatory and oversight policies, and ethical considerations by assessing the relative significance of issues in preventing LDLT growth, with proposed strategies to overcome barriers.
Results
Living liver donors endure multiple obstacles including financial instability, loss of job security, and potential morbidity. These concerns, along with other center, state, and federal specific policies can be perceived as significant barriers to expanding LDLT. Donor safety is of paramount importance to the transplant community; however, regulatory and oversight policies aimed at ensuring donor safety can be viewed as ambiguous and complicated leading to time-consuming evaluations that may deter donor motivation and program expansion.
Conclusion
Transplant programs need to establish appropriate crisis management plans to mitigate potential negative donor outcomes and ensure program viability and stability. Finally, ethical aspects, including informed consent for high-risk recipients and use of non-directed donors, can be perceived as additional barriers to expanding LDLT.

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https://onlinelibrary.wiley.com/doi/abs/10.1111/ctr.14967?campaign=woletoc

A survey of transplant providers regarding attitudes, barriers, and facilitators to living donor liver transplantation in the United States

AnnMarie Liapakis, Uchenna Agbim, Therese Bittermann, Mary Amanda Dew, Yanhong Deng, Geliang Gan, Sukru Emre, Heather F. Hunt, Kim M. Olthoff, Jayme E. Locke … See all authors
First published: 20 March 2023 https://doi.org/10.1111/ctr.14967Citations: 1
AnnMarie Liapakis and Uchenna Agbim are co-first authors.

Abstract
Introduction
A successful living donor liver transplant (LDLT) is the culmination of a multifaceted process coordinated among key stakeholders.
Methods
We conducted an electronic survey of US liver transplant (LT) centers (August 26, 2021–October 10, 2021) regarding attitudes, barriers, and facilitators of LDLT to learn how to expand LDLT safely and effectively in preparation for the American Society of Transplantation Living Donor Liver Transplant Consensus Conference.
Results
Responses were received from staff at 58 programs (40.1% of US LT centers). There is interest in broadening LDLT (100% of LDLT centers, 66.7% of non-LDLT centers) with high level of agreement that LDLT mitigates donor shortage (93.3% of respondents) and that it should be offered to all suitable candidates (87.5% of respondents), though LDLT was less often endorsed as the best first option (29.5% of respondents). Key barriers at non-LDLT centers were institutional factors and surgical expertise, whereas those at LDLT centers focused on waitlist candidate and donor factors. Heterogeneity in candidate selection for LDLT, candidate reluctance to pursue LDLT, high donor exclusion rate, and disparities in access were important barriers.
Conclusion
Findings from this study may help guide current and future expansion of LDLT more efficiently in the US. These efforts require clear and cohesive messaging regarding LDLT benefits, engagement of the public community, and dedicated resources to equitably increase LDLT access.

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https://onlinelibrary.wiley.com/doi/abs/10.1111/ctr.14968?campaign=woletoc

Advances and innovations in living donor liver transplant techniques, matching and surgical training: Meeting report from the living donor liver transplant consensus conference

Mark Sturdevant, Swaytha Ganesh, Benjamin Samstein, Elizabeth C. Verna, Manuel Rodriguez-Davalos, Vineeta Kumar, Marwan Abouljoud, Oya Andacoglu, Medhat Askar, Dieter Broering … See all authors
First published: 11 April 2023 https://doi.org/10.1111/ctr.14968Citations: 1
Mark Sturdevant and Swaytha Ganesh are co-first authors.
Nazia Selzner Sukru Emre are co-senior authors.

Abstract
The practice of LDLT currently delivers limited impact in western transplant centers. The American Society of Transplantation organized a virtual consensus conference in October 2021 to identify barriers and gaps to LDLT growth, and to provide evidence-based recommendations to foster safe expansion of LDLT in the United States. This article reports the findings and recommendations regarding innovations and advances in approaches to donor-recipient matching challenges, the technical aspects of the donor and recipient operations, and surgical training. Among these themes, the barriers deemed most influential/detrimental to LDLT expansion in the United States included: (1) prohibitive issues related to donor age, graft size, insufficient donor remnant, and ABO incompatibility; (2) lack of acknowledgment and awareness of the excellent outcomes and benefits of LDLT; (3) ambiguous messaging regarding LDLT to patients and hospital leadership; and (4) a limited number of proficient LDLT surgeons across the United States. Donor-recipient mismatching may be circumvented by way of liver paired exchange. The creation of a national registry to generate granular data on donor-recipient matching will guide the practice of liver paired exchange. The surgical challenges to LDLT are addressed herein and focuses on the development of robust training pathways resulting in proficiency in donor and recipient surgery. Utilizing strong mentorship/collaboration programs with novel training practices under the auspices of established training and certification bodies will add to the breadth and depth of training.