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Liver Transplantation in the United Arab Emirates From Deceased and Living Donors: Initial 2-Year Experience

Kumar, Shiva MD, MHA1; Miller, Charles M. MD2; Hashimoto, Koji MD, PhD2; Quintini, Cristiano MD2; Kumar, Arun MD3; Balci, Numan C. MD4; Pinna, Antonio D. MD, PhD1

Author Information
doi: 10.1097/TP.0000000000003455
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INTRODUCTION

Located at the southeast end of the Arabian Peninsula on the Arabian Gulf, the United Arab Emirates (UAE) is the second largest economy in the Gulf cooperation council, with a population of about 9.3 million. Until recently, one of the primary unmet medical needs in the country was the availability of solid organ transplantation. Historically, patients in the UAE in need of liver transplantation (LT) traveled abroad with most of them undergoing living donor liver transplantation (LDLT). However, patients without potential living donors had limited options. Moreover, patients presenting with fulminant hepatic failure often died while arrangements were being made for expedited transfer, underscoring the need to establish liver transplant in the country.

Propelled by the passage of the brain death law in May 2017, an extensive collaborative effort involving multiple key stakeholders resulted in the successful establishment of LT from deceased and living donors.

Current Status of Liver Transplantation in the Middle East

LT in the Middle East remains confined to a few countries and relies heavily on the availability of living donors. In many countries in the region, definition of brain death remains unclear, impeding the establishment of deceased donor organ transplantation.1 Two countries (Saudi Arabia [KSA] and Egypt) account for >90% of all liver transplants performed in the Arab world. Since the first deceased donor liver transplant (DDLT) in the region (KSA, 1990), growth of DDLT has been slow, accounting for <20% of all LT.2,3 As of 2013, only 7 countries in the region reported performing any DDLT and countries other than KSA collectively accounted for only 8% of all DDLT in 62 recipients.2

Burden of Liver Disease in the UAE

Limited data exist regarding the burden of liver disease in the region. Global assessments of disease burden have consistently identified liver disease as being among the top 10 causes of disease-specific mortality in the Arab world.4 Recent data point to nonalcoholic fatty liver disease (NAFLD) as the primary cause of end-stage liver disease. Global prevalence studies have identified the Middle East as the region with the highest prevalence of NAFLD.5 In addition, recent modeling data suggest a 2-fold increase in the burden of advanced liver disease and hepatocellular carcinoma related to NAFLD over the next decade, with liver-related mortality expected to account for 2.9% of all deaths in the UAE by 2030.6

Seminal Events Leading up to the Establishment of DDLT and LDLT in the UAE

Passage of the Law Defining Brain Death

Based on validated diagnostic modalities, standard criteria for definition of brain death have been used worldwide for confirmation of brain death, before proceeding to organ procurement.7 The legal definition of brain death in the UAE was confirmed in May 2017 by a decree from the Ministry of Health and Prevention, paving the way for deceased donor organ transplantation in the country. This enabled confirmation of brain death resulting from complete loss of brain function and led to the establishment of a network of donor hospitals to identify potential donors.

Collaborative Framework Between Key Entities and Stakeholders

Establishing solid organ transplantation had been identified as a key strategic initiative at Cleveland Clinic Abu Dhabi (CCAD) with the beginning of clinical activities in early 2015. Efforts to bring this to fruition involved close collaboration with other key stakeholders, including the Ministry of Health and Prevention, Department of Health in Abu Dhabi, Dubai Health Authority, UAE national transplant committee, Cleveland Clinic Foundation, Mubadala Healthcare, and Abu Dhabi health services company (SEHA), leading to the successful establishment of a multiorgan transplant center at CCAD and the initiation of LT from deceased donors within 9 months of the laws’ passage.

First Multiorgan Brain-dead Donor in the UAE and Development of LT From Deceased and Living Donors

The sequence of events detailed above led to the first brain-dead multiorgan donor in the UAE on July 15, 2017, with the procurement resulting in 2 deceased donor kidney transplants in the country. The first deceased donor liver transplant in the UAE was performed at CCAD on February 1, 2018. Scarcity of deceased donor organs mandated the establishment of LDLT to complement ongoing efforts to improve organ donation rates. LDLT was established in the UAE as part of a collaborative effort with the Transplant center at Cleveland Clinic’s main campus in Cleveland, Ohio resulting in the first successful LDLT in the country on July 29, 2018.

Initial 2-Year Experience

Transplant Selection and Allocation Policies

Oversight over identification of potential donors and allocation of organs in the UAE rests with the National transplant committee. At present, although CCAD serves as the country’s only multiorgan transplant center, there are 3 additional kidney transplant centers—1 in the Emirate of Abu Dhabi and 2 in Dubai.

The majority of residents in the UAE belong to the age category of 25–54 y, with expatriates comprising >85% of the population (fcsa.gov.ae/en-us). While the Government provides comprehensive health coverage for all UAE nationals, most expatriates and their dependents in the UAE have employer provided health insurance, with the extent of coverage varying based on policy terms (u.ae/en). As the only operational liver transplant center in the country, CCAD has a streamlined referral process for LT. All residents have access to CCAD’s liver transplant program, as long as they have coverage for transplantation. Recipients with indications for transplantation undergo a step-wise evaluation based on a standard transplant evaluation protocol. Additional tests are performed as clinically indicated and patients are listed after multidisciplinary team discussion. Recipients are prioritized on the waitlist based on the model for end-stage liver disease score with exception points awarded based on the most recent United Network for Organ Sharing (UNOS) guideline that is currently being followed in the United States (https://optn.transplant.hrsa.gov/media/2847/liver_guidance_adult_meld_201706.pdf; last accessed August 16, 2020).

Transplant Volumes Over the Past 2 Years in the UAE

In the first two years since inception, we performed 11 liver transplants from deceased donors and 14 LDLTs (overall: 4 right lobe and 10 left lobe grafts). Figure 1 highlights key milestones in our journey to establish LT in the UAE. Our experience underscores the challenges related to deceased donor organ availability and the role of LDLT in meeting the growing demand for LT.

FIGURE 1.
FIGURE 1.:
Timeline depicting key milestones in liver transplantation in the UAE. UAE, United Arab Emirates.

Recipient Characteristics

Five (20%) recipients were expatriates (4 of whom underwent DDLT), whereas the remainder were UAE nationals. Primary indication for LT was NAFLD (52%), followed by primary sclerosing cholangitis (12%). All 4 (16%) recipients with hepatocellular carcinoma had underlying cirrhosis from NAFLD. Two recipients (8%) each underwent LT for Wilson’s disease, cirrhosis secondary to chronic hepatitis B and autoimmune hepatitis. Two emergent LTs were performed—left lobe LDLT for fulminant Wilson’s disease and DDLT for early graft dysfunction following LDLT.

Recipient characteristics are outlined in Table 1. Median recipient age was 51 y (range, 21–73) with a median model for end-stage liver disease score at transplant of 18 (range, 9–40). NAFLD was the principal indication for LT, which is consistent with the regional prevalence of NAFLD in the region.

TABLE 1. - Characteristics of liver transplant recipients and donors
Recipients n (%)
Gender
° Male 12 (48)
° Female 13 (52)
Nationalities
° UAE nationals 20 (80)
° Expatriates 5 (20)
Cause of liver disease
° NAFLD 13 (52)
° PSC 3 (12)
° AIH 2 (8)
° HBV 2 (8)
° Wilson’s disease 2 (8)
° Fulminant hepatic failurea 2 (8)
Hepatocellular carcinoma 4 (16)
Variable Median (range)
° Recipient age 51 (21–73)
° Recipient BMI 25 (13.9–38)
° Recipient MELD Score at transplant 18 (9–40)
Donors n (%)
Gender
° Deceased donors—male:female 8 (73):3 (27)
° Living donors—male:female 9 (65):5 (35)
Nationalities
° Deceased donors—UAE nationals:expatriates 0 (0):11 (100)
° Living donors—UAE nationals:expatriates 13 (93):1 (7)
Mean age (y) Range
° Deceased donors: 34.5 16–47
° Living donors: 32 20–39
aOne patient with fulminant presentation of Wilson’s disease.
AIH, autoimmune hepatitis; BMI, body mass index; HBV, hepatitis B virus; MELD, model for end-stage liver disease; NAFLD, nonalcoholic fatty liver disease; PSC, primary sclerosing cholangitis; UAE, United Arab Emirates.

Donor Characteristics

Mean age of deceased donors was 34.5 y (range, 16–47), whereas that of living donors was 32 y (range, 20–39). All deceased liver donors were expats, whereas all but 1 of the living donors were UAE nationals. All living liver donors were related to recipients, as required by UAE law. In total, 73% and 65% of deceased and living donors, respectively, were male (Table 1).

Living Donor Outcomes

All living donors recovered uneventfully with a median duration of hospitalization of 6.5 d. None of the donors required reoperation or developed complications ≥3 on the Clavien-Dindo grading system.8

Recipient Outcomes, Graft and Patient Survival

Two recipients underwent unplanned reoperation within 30 days of LT. Four (17%) recipients developed acute cellular rejection. All episodes were mild-moderate and responded to either escalation of immunotherapy or pulse steroids, with the exception of 1 severe episode due to noncompliance. Cytomegalovirus viremia was noted in 11 recipients, with invasive disease (retinitis) occurring only in 1 recipient. Four DDLT and 6 LDLT recipients developed biliary strictures, all of which were anastomotic in nature and responded to endoscopic therapy, with the exception of 4 post-LDLT strictures that required >3 endoscopic procedures. None of the recipients developed vascular complications.

At the time of last follow-up, all of our liver recipients were alive with functioning grafts. A total of 20 recipients have completed at least a year of follow-up, with 1-y actuarial graft and patient survival of 100% and 100%, respectively. The overall patient and graft survival for the 24 patients and 25 grafts after a median follow-up period of 647 days (range, 247–1002) were 100% and 96%, respectively. The solitary graft loss occurred because of portal vein steal syndrome via coronary vein shunt following left lobe LDLT causing graft dysfunction, necessitating emergent DDLT.

Summary and Future Considerations

We report the successful establishment of LT in the UAE, from both deceased and living donors and our results after the first 2 operational years. The predominance of NAFLD among indications for LT is noteworthy. Our early results and outcomes—graft and patient survival, recipient and donor morbidity, and resource utilization—compare very favorably to countries with established transplant programs, while highlighting the challenges related to scarcity of deceased donor organs and the need for continued growth of LDLT to meet demand in the region.

The paucity of established liver transplant programs from deceased donors in the region underscores the significance of our experience and holds important lessons for other countries in the region and beyond. The continued growth and success of LT will ensure that patients with liver disease in need for transplantation in the UAE and broader Gulf region will have seamless access to transplant services without having to travel long distances.

The expected increase in demand for LT could only be addressed by robust efforts at improving awareness of organ donation. Cultural and religious considerations regarding organ donation have historically limited growth of deceased donor organ transplantation in the region.1,9,10 This is being addressed in collaboration with religious and cultural authorities. Ongoing initiatives to improve awareness regarding organ donation include the creation of a national digital organ donor registry and plans to include consent for organ donation in the Emirates national ID card, which is a requirement for all residents in the country. Additionally, a national strategy aimed at addressing the increasing burden of disease related to NAFLD is warranted, given the high prevalence of NAFLD among liver recipients.

Future initiatives to help address the supply-demand gap include consideration of extended criteria donors, including donation after circulatory death, as well as improved collaboration with other countries in the region to help meet demands of critically ill patients.

ACKNOWLEDGMENTS

The authors acknowledge the efforts and contributions of the multidisciplinary liver transplant team and leadership at CCAD, Cleveland Clinic Foundation, Mubadala Healthcare, UAE National Transplant Committee, UAE Ministry of Health and Prevention, Department of Health in Abu Dhabi, and SEHA.

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