Travel for Transplantation: A Review of Domestic and International Travel for Liver Transplantation in the United States

Short abstract

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Abbreviations

CI

confidence interval

DOI

Declaration of Istanbul

LT

liver transplantation

MELD

Model for End‐Stage Liver Disease

ML

multiple listing

NCNR

noncitizen nonresident

NC‐R

noncitizen resident

RR

relative risk

SL

singly listed

UNOS

United Network for Organ Sharing

WL

wait list

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KEY POINTS

• Despite legislation that mandates organs should be allocated based on medical necessity only, geographic disparities in access to transplantation persist throughout the United States.

• Travel for transplant within the United States, and to the United States, is permissible, but is only practically accessible for a minority of patients who have the medical fitness, financial resources, and flexible insurance to take advantage of these policies.

• The practice of traveling for transplant violates the spirit of social justice on which our organ allocation system was founded by rewarding a small subset of the population and harming institutional, regional, and national self‐sufficiency. The United Network for Organ Sharing (UNOS) emphasizes transparency in reporting, and several studies have aimed at characterizing travel behavior over the past 10 years, but to our knowledge, a comprehensive review of this material, as it relates to liver transplantation (LT), does not exist.

The Declaration of Istanbul (DOI) was created in 2008 by The Transplantation Society and the International Society of Nephrology with the intent of expanding the practice of transplantation without relying on unethical or exploitative processes. This document was updated in 2018, and it has served as the ethical foundation for transplantation since its creation, with endorsements by 135 national and international medical societies and governmental bodies involved in transplantation. ¹ Among many edicts, the DOI specifically condemns human and organ trafficking and emphasizes the importance of individual countries continuing to strive toward self‐sufficiency.

The DOI defines travel for transplantation as “the movement of persons across jurisdictional borders for the purposes of transplantation,” and further specifies that jurisdiction “encompasses not only nations but also states, provinces, other formally defined areas within countries, and regional or other supra‐national legal entities with the authority to regulate organ donation and transplantation.” ¹ In this light, the phenomenon of travel for transplantation is multifaceted in the United States, where transplant candidates may engage in both domestic and international travel.

Domestic travel for transplantation in the United States is fueled by geographic disparities in access to transplantation ² and takes the form of multiple listing (ML), whereby transplant candidates are listed at more than one US center to maximize their chance for transplant. Although ML is a potential option for all LT candidates, in actuality, only 4.3% of liver candidates ³ actually pursue this option, because it can be practically limited by insurance, financial resources, and social support. International travel for transplant in the United States includes those who travel from the United States and those who travel to the United States. Travel outside the United States is generally discouraged for US patients, although there continue to be individuals who engage in this practice. Travel to the United States from other countries is more common; patients from other countries pursue transplantation in the United States as either noncitizen residents (NC‐Rs) or noncitizen nonresidents (NCNRs). In this article, we review the literature on both domestic and international travel for transplantation within the United States to describe the collective impact that these practices have on LT in the United States.

Domestic Travel for Transplant

Since 2014, eight peer‐reviewed publications have focused on domestic travel for transplant ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ (Table 1). Kohn and colleagues ⁴ reviewed 44 ML LT recipients and 279 singly listed (SL) recipients from their center between 2005 and 2013. Longer time on the wait list (WL) and private insurance were associated with ML status, and 5‐year post‐transplant survival rate was lower in ML patients (63% versus 80%; P = 0.03). Schwartz et al. ⁵ investigated ML recipients (n = 27) and SL patients who died on the WL (n = 120) at a single center and found that ML patients had significantly higher median incomes, and both lower median income and Medicaid insurance were associated with an increased likelihood of death on the WL. Studies using UNOS data found that ML patients are more often white, male, privately insured, more highly educated, more likely to have cholestatic liver disease, and less likely to have alcoholic liver disease or hepatitis C. ³ , ⁶ , ⁷ , ⁹ ML patients have an increased likelihood of progression to LT in most studies, ³ , ⁶ , ⁸ , ⁹ and one study found no difference in 5‐year posttransplant graft or patient survival when comparing ML versus SL patients. ⁷

TABLE 1.

Summary of Studies Examining Domestic Travel for LT

Year Published	First Author	Design	Years of Study	Sample Size	Major Outcome(s)
2014	Kohn 4	Retrospective, single‐center cohort	2005‐2013	ML transplant recipients: 44	Wait time: significantly longer for ML versus SL (930 versus 354 days; P < 0.001) Factors associated with ML: longer time on list, private insurance Most common regions traveled to: 3 and 10 1‐ and 5‐year posttransplant survival: 81% ML versus 90% SL, P = 0.09; 63% ML versus 80% SL, P = 0.03, respectively
				SL transplant recipients: 279
2014	Schwartz 5	Retrospective, single‐center cohort	2009‐2011	ML recipients: 27	Financial and insurance differences among cohorts:
				SL WL deaths: 120	‐Median income $60,244; median income ML $84,946 versus WL death $55,250; P = 0.0001 ‐Median income <$60,244 associated with increased likelihood of death (94% versus 70%, RR: 1.35, 95% CI: 1.14‐1.59) ‐Medicaid insurance associated with increased likelihood of WL death (100% versus 77%, RR: 1.30, 95% CI: 1.18‐1.44)
2014	Vagefi 6	Retrospective, UNOS cohort	2005‐2011	ML candidates: 1358	Demographic differences: ML more often male, white, college‐educated, privately insured, cholestatic liver disease, longer time on WL WL outcomes: ML longer wait times, more likely to undergo transplant versus SL (67% versus 52%) Regional utilization: ML most frequently from regions 1, 5, and 9
				SL candidates: 58,199
2015	Croome 7	Retrospective, UNOS cohort	2008‐2013	ML recipients: 2355	Demographic differences: ML more often male, white, cholestatic liver disease, privately insured Posttransplant outcomes: no difference in 5‐year graft or patient survival between ML and SL recipients
				SL recipients: 26,345
2016	Cholankeril 8	Retrospective, UNOS cohort	2010‐2015	ML candidates: 1082	Probability of undergoing LT by staying in primary versus secondary region: 80% ML versus 46% SL Regions: >75% of ML candidates from regions 1, 5, 7, and 9 and 46% of ML transplants performed in region 3 ML versus SL: ML shorter time to transplant, higher probability of transplant, lower MELD at transplant
				SL candidates: 68,998
2017	Cholankeril 9	Retrospective, UNOS region 5 cohort	2010‐2015	ML recipients: 304	Demographic differences: ML male, graduate degrees, higher income Probability of transplant: ML 83% versus SL 36%
				SL recipients: 4679
2018	Goldberg 10	Retrospective, UNOS cohort	2017	Domestic tourists: 318	Description of domestic tourists: 26% from California Description of destinations:
				Nontourists: 6629
					‐48.4% of patients traveled to Ochsner, Mayo‐Rochester, Mayo‐Jacksonville, Mayo‐Scottsdale ‐11 states transplanted ≥10 domestic tourists ‐8 centers performed >12% center volume on domestic tourists
2020	Brown 3	Retrospective, UNOS cohort	2002‐2016	ML: 3584	1. Benefit of ML: greatest for patients with MELD < 15
				SL: 80,351

Geographic trends were also examined. Vagefi et al. ⁶ found that ML patients were most frequently from regions 1, 5, and 9. Cholankeril and colleagues ⁸ found that 75% of ML patients derived from regions 1, 5, 7, and 9, and approximately 46% of the transplants for ML patients were performed in region 3. Goldberg and Lynch ¹⁰ reported that 26% of ML patients were from California specifically, 50% of ML patients pursued transplant at one of four centers (Ochsner Clinic, Mayo‐Jacksonville, Mayo‐Rochester, or Mayo‐Scottsdale), only 11 states transplanted ≥10 ML patients, and 8 centers performed more than 12% of their center volume on ML patients.

International Travel for Transplant

A total of four peer‐reviewed publications relating to international travel for transplant ¹¹ , ¹² , ¹³ , ¹⁴ (Table 2) and one addressing domestic and international travel have been published since 2014. In 2015, Goldberg and Schiano ¹¹ reported that from 2005 to 2013, 366 LTs were performed in NCNR patients in the United States. Delmonico and colleagues ¹² identified 351 NCNR LTs performed between 2013 and 2016 and found that 7 transplant centers performed more than 5% of their annual center volume with NCNR transplants. Ferrante and Goldberg ¹³ reviewed 1260 NCNR transplants between 2002 and 2016; NCNR recipients were less likely to die or be removed from the WL for being too sick, had better posttransplant survival, and were more likely to be lost to follow‐up. In 2020, Lee and Terrault ¹⁴ examined unauthorized immigrants, classified as NCNRs who traveled to the US for reasons other than LT, and found no difference in graft or patient survival among unauthorized immigrants and the remainder of the cohort between 2012 and 2018, but found that unauthorized immigrants were significantly more likely to be lost to follow‐up. Most recently, our group examined both domestic and international travel for LT and found that, compared with SL patients, ML patients underwent LT at lower Model for End‐Stage Liver Disease (MELD) scores and were less likely to be removed from the list for any reason, while NCNR patients were more likely to undergo transplant and be removed from the list for other reasons.

TABLE 2.

Summary of Studies Examining International Travel for LT

Year Published	First Author	Design	Years of Study	Sample Size	Major Outcome(s)
2015	Goldberg 13	Retrospective, UNOS cohort	2005‐2013	366 nonstatus 1 foreign national deceased donor LT recipients	Quantifying burden of foreign national LTs
2018	Delmonico 12	Retrospective, UNOS cohort	2013‐2016	351 NCNR transplants	Quantifying burden of foreign national LTs Identifying centers performing disproportionate number of transplants in foreign nationals: 7 centers performed >5% center volume in NCNRs
2018	Ferrante 13	Retrospective, UNOS cohort	2002‐2016	NCNRs: 1260	WL outcomes: NCNRs less likely to die/be removed for being too sick Posttransplant outcomes: NCNRs significantly better posttransplant survival Lost to follow‐up: NCNRs significantly more likely to be lost to follow‐up
				Citizens/Residents: 145,790
2020	Lee 14	Retrospective, UNOS cohort	2012‐2018	Unauthorized immigrants: 166	Descriptive data Posttransplant outcomes: no difference in graft or patient survival for unauthorized immigrants versus residents Lost to follow‐up: unauthorized immigrants more likely to be lost to follow‐up
				Residents: 43,026
2021	Braun 16	Retrospective, UNOS cohort	2003‐2017	ML: 6625	Descriptive data WL outcomes: ML, NCNRs more likely to proceed to transplant, NC‐Rs more likely to be removed from list for death/too sick Posttransplant outcomes: SL worst graft, patient survival
				NCNRs: 1223
				NC‐Rs: 4811
				SL: 119,618

Discussion

The sum of literature on domestic travel for LT characterizes ML recipients as predominantly white, male, privately insured, highly educated, and with a larger proportion of cholestatic liver disease and finds that the practice of ML is not spread uniformly across the country, but rather clustered in a minority of regions, states, and centers. The literature on international travel for LT in the United States suggests this is a rare problem, accounting for approximately 1% of LTs and clustered at a handful of centers, but it is a concerning problem in that NCNR patients may have better outcomes compared with SL patients and may cause SL patients to wait longer and push potential deterioration or become too ill for transplant.

A subtlety of the DOI is that travel for transplant becomes transplant tourism, and thereby unethical, when the resources “devoted to providing transplants to non‐resident patients undermine the country's ability to provide transplant services for its own population.” ¹ Given that the US demand for LT continues to dramatically outpace the available supply, one could argue that any travel for transplantation in the United States undermines our ability to provide transplantation for our population and is therefore transplant tourism. However, as explained in a 2015 review by Gill and Delmonico, ¹⁵ not all travel for transplantation is unethical; patients with dual citizenship, patients seeking medical or surgical expertise, and established collaborations are among the acceptable forms of travel for transplantation. What this review of the US literature suggests, however, is that both the need and ability to travel for transplantation are restricted to the upper echelons of our society and disproportionately impact certain regions and centers within the United States. Furthermore, although there is no level 1 evidence to this effect, it appears that patients who have the means to travel enjoy superior pretransplant and posttransplant outcomes, which fundamentally undermines the spirit of social justice on which our organ allocation system was founded.

Conclusion

The purpose of the US organ allocation system for LT is to provide fair access to LT and to prioritize the patients with the greatest medical urgency. The practices of domestic and international travel for transplantation have allowed patients to expedite their time to transplant within the LT system in this country, but we need to critically evaluate whether these practices are ethically acceptable when we continue to have nonzero WL mortality. Furthermore, live donor LT remains nowhere near its potential in the United States and may represent an alternative solution that does not require drawing from the limited deceased donor pool; this has yet to be explored in depth in the traveler population.