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Current status of liver transplantation in Latin America
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Current status of liver transplantation in Latin America Alan G. Contrerasa,∗, Lucas McCormackb, Wellington Andrausc, Eduardo de Souza M Fernandesd, on behalf of the Latin America Liver Transplantation Group (Alan G. Contrerase, Lucas McCormackf, Wellington Andrausg, Eduardo de Souza M. Fernandesg, Alejandro Serrablo Requejoh, Nicolás Jarufei, Martin Dibi, Felix Carrascoj, Martin Harguindeguyk, Jose Pablo Garbanzol, Frans Serpam, Alejandro Gimenezn, Ricardo Villaroelo, Alonso Verap) a
Department of Surgery, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico Department of Surgery, Hospital Aleman, Buenos Aires, Argentina Digestive Organs Transplant Division, Gastroenterology Department, Sao Paulo University School of Medicine, Sao Paulo, Brazil d Department of Surgery, Rio de Janeiro Federal University, Department of Surgery and Abdominal Organ Transplant, São Lucas Hospital, Copacabana, Brazil e Mexico f Argentina g Brazil h Spain i Chile j Peru k Uruguay l Costa Rica m Ecuador n Paraguay o Bolivia p Colombia b c
A R T I C LE I N FO
A B S T R A C T
Keywords: Liver transplantation Latin America
The lack of adequate financial coverage, education, and the organization has been the main limiting factor for the development of transplantation in Latin America. As occurred worldwide, the number of patients on liver waiting lists in Latin America grows disproportionately compared to the number of liver transplantations (LTs) performed. Although many law modifications have been made in the last year, most countries lack social awareness about the importance of donation and the irreversibility of brain death. The mechanisms and norms for organ procurement and infrastructure development, capable of supporting this high demand, are still in slow progress in most countries. Access to LT in the region is very heterogeneous. While some countries have no active LT programs so far, others are an international model of a public transplantation system (Brazil) or a national information system (Argentina). While some countries have only a few LT centers, others have too many LT centers performing an inadequate low number of LTs. Disparity to access transplantation remains the major challenge in the region. Cultural and educational efforts have to be accompanied by transparent public policies that will likely increase organ donation and activity in transplantation. The purpose of this article is to review the trends and current activity in LT within Latin America, based on prior publications and the information available in each country of the region.
1. Introduction Surgery in Latin America was developed with the influence of European and North American schools of surgery. In the 1970s and 80s,
many surgeons from the region were trained at centers of liver transplantation (LT) in North America and Europe, returning to their native countries to set up their units of transplantation. However, the lack of adequate financial coverage, education, and organization has been the
∗ Corresponding author. Department of Surgery, Transplant Division, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez Secc 16, Tlalpan, 14080, Ciudad de México, CDMX, Mexico E-mail address: [email protected] (A.G. Contreras).
https://doi.org/10.1016/j.ijsu.2020.03.039 Received 6 February 2020; Received in revised form 6 March 2020; Accepted 18 March 2020 1743-9191/ © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Alan G. Contreras, et al., International Journal of Surgery, https://doi.org/10.1016/j.ijsu.2020.03.039
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2. How is liver allocation in Latin America?
Abbreviations
Organ allocation systems have been developed to distribute organs more equitably based on the fact that there are not enough donated organs to transplant everyone in need. The scarcity of organs for LT in Latin America is the most important factor leading to the deaths of patients on waiting lists. The need for liver transplantation is different due to the differences in the epidemiology of liver disease and the organization of health care [1,2]; some countries have a disproportionated low number of patients in the waiting list exposing other important factors including a disproportionated access to high quality health care. Therefore, the equitable allocation of donated organs to patients who need them the most on the waiting list is crucial. Liver allocation policy in most countries of Latin America was initially based on a patient's location of care and time on the waiting list. The social and political requests for a better allocation system focusing on the patient's severity of underlying liver disease led to the implementation of the allocation policy based on the model for end-stage liver disease (MELD score) in some countries of the region (Table 1). In 2005, Argentina was the first country after the US to adopt the MELD system for LT. Implementation of the MELD scoring system improved organ allocation but, unfortunately, this new policy has no change the waiting list mortality [3]. Socio-economic factors and differences between the US and Latin American countries’ health systems may explain why patient survival on some Latin American waiting list was no significantly improved after MELD. Despite different organ allocation systems across Latin America, the principles of utility and justice remain, however, there is still a lag in the evolution of public policies regarding organ allocation and transplantation, for instance, some countries have predominantly center-based allocation system. (e.g. Mexico), whereas most have moved toward recipient-based systems utilizing MELD or MELD-Na for the allocation. As expected, the critiques argue that MELD score may not sufficiently prioritize certain patient populations and give an unfair benefit to other subpopulations [3]. However, the only way to ameliorate the conflict between utility and justice is by increasing the supply of donor organs. An analysis of specific variables including cultural, logistic and socio-economic factors would potentially help in optimizing these principles in each country individually.
LT DCD
liver transplantation donation after circulatory death LDLT = Living donor liver transplantation PMP= Per Million of Population MELD Model for end-stage liver disease MELD-Na Model for end-stage liver disease- Sodium HCV= Hepatitis C Virus HBV Hepatitis B Virus NAFLD Nonalcoholic fatty liver disease HCC= Hepatocellular Carcinoma
main limiting factors for the development of liver surgery and transplantation in Latin America. When compared with Europe or the US, in Latin America the donation rate is dramatically lower (Fig. 1). Additionally, the activity in LT is very different throughout all the Latin American countries whereas countries like Argentine and Brazil perform more than 10 LT per million of population (PMP) and countries like Venezuela, Dominican Republic, Paraguay and Bolivia around 0.2 to 0.4 PMP. Moreover, LT is not performed in 7 countries of Central America including Guatemala, Trinidad y Tobago, Honduras, Nicaragua, Panama, El Salvador, and Haiti. Among the countries with active LT programs in Latin America, pediatric live donor LT programs have been performed in only 7 countries and only in 4 for adults with the intention to palliate the organ shortage and mortality on waiting lists (Table 1). In 2019, Brazil, Chile, México and Colombia were the only countries performing a live donor adult-to-adult LT among the region. To date, no team in the region have developed a Donor after Circulatory Death (DCD) LT program to palliate donor shortage. There are not supplementary incentives for deceased or living donors in the region and organ trafficking is prohibited and punished by law in Latin America. The purpose of this article is to review the trends and current activity in LT within Latin America, based on prior publications and the information available in each country of the region. To note, data regarding current LT activity in the Dominican Republic, Cuba and Venezuela were not available for the authors of this article. As transplant services available in Puerto Rico comply with federal rules and standards under the Organ Procurement and Transplantation Network/ United Network for Organ Sharing, its information was not included in this article.
Fig. 1. Annual Deceased Donor Organ Rate in 2019 among countries of the region (PMP: Per Million Population). 2
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Table 1 Statistics referred to each Latin American country with active centers performing liver transplantation in 2019. They are listed by number of transplants performed during 2019.
Brazil Argentine México Chile Colombia Perú Ecuador Uruguay Costa Rica Paraguay Bolivia
Population (millons)
Initiation of LT
LT centers
Donation rate (PMP)
LT annual rate (PMP)
DDLTs
Pediatric LDLTs
Adult LDLTs
210.1 43.4 127 17.9 48.2 32.5 16.1 3.4 4.8 7.2 11
1968 1988 1985 1985 1979 2000 2000 1998, 2009 1993 2015 1996
60 33 80 9 9 4 5 1 3 1 2
17.7 19.6 4.1 10.4 8.2 2.3 4.9 23.4 (2018) 4.7 5.7 1.1
10.4 10.8 1.5 9.1 5 1.6 1.8 7 3.9 0.3 0.3
2006 429 213 145 207 46 30 24 19 2 0
136 42 8 6 50 6 0 0 0 0 3
22 0 2 12 2 0 0 0 0 0 1
LT: Liver Transplantation; DDLT: Deceased Donor Liver Transplantation; LDLT: Live Donor Liver Transplantation; PMP: per million population; N/A: Not Available.
Other methods to increase the liver transplant rates include the development of active split liver programs (e.g. Argentina), domino transplantation, live donation program and, today, active utilization of donation after cardiac death donors that has not been applied in the region for LT [6].
2.1. Is the supply of deceased donor organs adequate? Organ donation in Latin America The donation rate in Latin America had a continuous increment throughout the last decade [4], however, it has been quite different among the countries. The supply of deceased donor organs varies according to the legal framework for donation and the population's attitude toward organ donation, and the interest and organization of the health care system regarding transplantation. Many countries had a donation rate above the average such as Uruguay, Argentina, and Brazil (Table 1). Unfortunately, a high rate of refusal to donate is still a major obstacle. For example in Brazil, the largest country of the region, of all federative units in Brazil, in 13 states the refusal rate exceeded 50%, reaching 80% in Mato Grosso and 74% in Sergip [5]. Probably, the surrogate factor is the lack of knowledge to understand that brain death is a situation of absolute irreversibility and not a reversible coma. Another area of opportunity is to increase the utilization of organs from potential donors that are not identified nor reported. In this sense, public policies should be in place to incentivize hospitals and health care providers to see this as opportunity of life for other patients and a legal framework and a system in place should facilitate the process. This could be a potential source of donors that are discarded in good condition. Additionally, once the donor is identified, several factors might influence the success of the multi-organic procurement such as inaccurate clinical evaluation of the potential donor; improper body maintenance; delays due to distance and accessibility by the organ removal teams; technical problems at the retrieval operation, problems with the organ mobilization or packing conditions; long cold ischemia time, among others, and they all should be taken into consideration as potential areas of opportunity to increase the utilization of organs.
2.2. Legislation for organ donation and transplantation Many important legal issues have been clearly documented in the transplantation laws of most Latin American countries including brain death diagnosis criteria, the type of consent for retrieval, the concept of altruistic living related donation, restrictions for living unrelated donation, medical criteria for allocation and a clear prohibition of organ commercialization [4]. Creating a presumed donor law was a move many countries have made trying to solve the organ donor crisis that affects the region. With this, unless the deceased person had left explicit instructions, relatives were given the final decision regarding organ donation. In other words, as established in the Spanish model, the families of each organ donor are consulted systematically before donation proceeds and they must give their final consent for organ donation. However, family refusal is the most important limitation of cadaveric donation once the donation process has been initiated. As a reaction to this difficult scenario, a “hard” presumed donor law aiming to drastically reduce the waiting time for those needing a transplant and hoping to reduce mortality on the waiting list has been implemented recently in Argentine. Today in Argentine, all adults over 18 are organ donors unless they expressly indicate otherwise before death, regardless of the familiar opinion. Interestingly, after the implementation of the so-called “Justina Law” in Argentina, in honor to a pediatric patient who died on
Table 2 Allocation policy, legislation and waiting list variables in each Latin American country in 2019. Consent for donation. Law modification (Year)
Family consultation
Allocation system
Waiting list (national/regional)
Mortality liver WL (%)
Argentine
Presumed consent (2005). (2019)
NO
National. Unique
16.2
Brazil Chile
Presumed consent (2006) Presumed consent (2019)
YES YES/NO
Regional National. Unique
N/A 29.6
Perú
Informed consent (2008)
YES
Presumed consent (2009) Presumed consent (2000) Presumed consent (2014) Presumed consent (2013) Presumed consent (2019. Ley Anita) Informed consent (1996) Presumed consent (2004, 2016)
YES YES YES YES NO YES YES
NationalUnique (regional for emergency) National (only adults) Unique. Center-oriented National National National National Regional
30
Uruguay México Costa Rica Ecuador Paraguay Bolivia Colombia
MELD- Na National exception committee MELD MELD- Na National exception committee MELD National exception committee MELD- Na Exception rules Center-oriented MELD-Na MELD MELD MELD Center-oriented/MELD
N/A: Not Available. 3
9 N/A N/A 8% 33% 50% 5,7
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on the waiting list are disproportionately low. Unfortunately, in many regions, educational, geographical, cultural and financial barriers along with different access to high Quality health care are limiting the access of cirrhotic patients to active LT programs and many patients needing a LT are dying outside the waiting list. We must state that the region is very heterogeneous and some issues regarding LT access, legislation and allocation need specific discussion for each country. Although LT activity was initiated many years ago in a few countries including Cuba (1986). Dominican Republic (2007) and Venezuela (1989) according to the STALYC report, the data regarding access to LT in 2019 was not available at the time of this review [4]. Brazil: The first LT was performed in 1968, the first successful LT (1985) and also the first live donor LT (1988) were performed by the team of the Liver Unit of the São Paulo Medical School, São Paulo University. Brazil is the largest country in Latin America, the second in number of liver transplants in the Western world and the first in Latin America. In 2019, more than 2000 deceased donor LT were performed being the highest number of LTs in the region, however because of the big population, the rate per million of population is only 10.4, and the total estimated need number of LT is 5500 per year, leading to a big waiting list and a high wait list mortality. Development of live donor LT (LDLT) for children and adults is the largest of the region (Table), on the other hand, while the number of deceased donors and deceased donor liver transplant (DDLT) keep growing year by year, LDLT number has been stable for many years and count for around only 8% of the total number of LTs [8]. Nowadays, Brazil is pioneering in the region the inclusion of novel indications for LT such as intra-hepatica cholangiocarcinoma and unresectable colorectal liver metastases fulfilling very strict criteria. As these are experimental indications so far, DDLT is not possible due to organ shortage problem and living donor liver transplant (LDLT) seems to be the only available alternative in Brazil. The first report of patient with colorectal liver metastases who underwent LDLT in Latin America was recently performed in Rio de Janeiro [9]. As a consequence of the big geographical area, an important regional disparity within the country challenge the equal access for LT of the population. Some regions are thousands of kilometers from LT centers. In Brazil, LT is only available in just 14 of the 26 states. The patients are listed in regionals waiting lists, each state that has
the cardiac waiting list, a similar scenario motivated legislators in Paraguay to recently also implement the so-called “Anita Law”, honoring to another patient who died waiting for a heart in Asunción. Although a significant increment in donation rate has occurred in Argentina reaching a record an annual donate rate of 19.6 PMP in 2019, its impact on the Paraguay donation rate was not positive so far. As a cascade effect, Chile has decided to introduce also the “hard” consent policy in the following months of 2020. Adequate legislation in each country is crucial to improve organ donation. In the region, the “presumed consent” countries have higher donation rates (Tables 1 and 2), however it is important to acknowledge that this might be a reflection of the interest of the population and legislators in those countries to increase organ donation and transplantation activity. Others have shown that places where the decision of donation is left to the donors (Opt-In) has better results than presumed consent (Opt-out) probably due to prioritizing of individual autonomy in a rights-based culture [7]. Legislation has to go further than Opt-in or Opt-out policies and a complete legal framework in the entire process including the detection of potential donors and expedite legal steps to allow donation, the organ harvesting, organ allocation and transportation and finally the practice of regulated and supported transplant centers will increase transparency, donation and transplant activity. 2.3. Access to liver transplantation and mortality on waiting list The number of LT performed in Latin America has grown constantly over the last years being Brazil the largest country in numbers of LT performed in 2019 (Fig. 2). However, there is an important gap between the donation rate and the LT annual rate probably due to the fact than most procurements are only performed for kidney transplantation (Fig. 3). The underlying problem is maybe poor donor maintenance, an excessive number of suboptimal donors or an inadequate infrastructure to organize multi-organic procurement due to logistic or geographical difficulties. Mortality in the LT waiting list varies among the regions being very high in countries such as Chile, Peru, Paraguay and Bolivia. This situation forced the groups of Chile to develop Adult-to-Adult LT programs in the country to improve access to LT. However, the mortality on the waiting list alone is not a good marker of access to LT in the region and might underestimate the mortality of patients that could potentially benefit of liver transplantation in countries where patients
Fig. 2. Annual Deceased Liver Transplantation rate in 2019 among countries of the region. 4
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Fig. 3. Deceased Donor Liver Transplantation performed in 2019 among countries of the region.
transplantation activities. This tool allows transparency, traceability and quality of procedures and is a model of the region. Donation and transplantation costs are funded by the health care system. Public or private health care institutions must be accredited for retrieval and transplantation, and health care professionals must be certified. Brain death must be certified by whole brain death criteria according to law. Presumed consent is the current legal requirement for donation from deceased donors. Law only allows organ donation from living related donors. In 2005, Argentina introduced a “soft” presumed consent policy for organ donation, where all people over 18 years of age will be organ donors unless they or their family state their negative. In 2019, a new law passed removing the family consent for organ donation (so-called “hard” presumed consent). This policy makes the potential donor “alive” the only person that can state their negative. Argentina's National Institute for the Coordination of Ablation and Implantation (INCUCAI) has informed that after the implementation of the new transplantation law in 2019, a significant increment in donation rate has occurred. However, the removal of the family consent after donor death is a controversial issue that remains under discussion within the transplant community. All patients are listed in a “unique national” waiting list, and thus, there is no allocation of organs from deceased donors to regional or LTcenters. On liver WL there are two major categories: emergency and elective candidates. Emergency status receives top priority on the WL all LT elective candidates listed in Argentina were re-categorized using the MELD score for organ allocation since 2005 [3]. When the MELD score may not estimate the severity of illness, each center can request a National Experts Committee for additional “priority” points [16]. Medical conditions that qualify for additional MELD points include familial amyloidotic polyneuropathy (16 points), hepatopulmonary syndrome (20 points) and T2 stage hepatocellular carcinoma. Each center can also request additional points for other conditions that diminish quantity or quality of life but are not included in the MELD score. Unfortunately, due to MELD system limitations, the extra-MELD points are frequently requested being today more than 50% of the LTs performed in the country based on extra-MELD points [16]. Chile: The first adult liver transplant in Chile occurred in 1969, although the patient passed at the end of the intervention. The first successful liver transplant was performed in 1985 at the Military Hospital of Santiago de Chile by Juan Hepp. The first successful pediatric transplant with a living related donor was performed in 1999 by Erwin Buckel and colleagues at Las Condes Clinic, in the same city. Currently, there are 9 active centers for LT in Chile, including 2
transplant centers has its own waiting list. São Paulo has the biggest population, 45 million people, and with the biggest waiting list, thus it is the only state with two regionals, the capital plus the coast and the countryside. In 1998, following some other countries worldwide, Brazil also tried a presumed consent for organ donation, where everybody was donor unless the person registered “NO” in his ID. Unfortunately this step resulted in a negative impact in organ donation, and three years later the National Transplant System came back to the family consent that is still working today. The Associação Brasileira de Transplante de Órgãos – Brazilian Association of Organ Transplantation, is the source of Brazilian statistical data [10]. According to the most recent report, in 2019 the country reached a rate of 17.7 donors PMP, and two states of Brazil had more than 40 donors PMP, showing a big potential for the country. Argentine. In 1988, de Santibañes at the Hospital Italiano of Buenos Aires carried out the first adult LT in Argentine. This team was a pioneer in the region, by also performing other procedures including pediatrics LT, split LT for children (1992), a live donor in a pediatric (1992) and an adult patient (1998) [11]. This team contributed to surgical education in the HPB field developing the first fellowship program in the region (1992) and collaborated in training surgeons not only in Argentina but also in neighboring countries. Today there are 33 active LT programs in Argentina being the vast majority in Buenos Aires. Unfortunately, as a result of the low donation rate, many LT programs have performed less than 10 transplants per year in the country in 2019. Today, most LTs are performed from cadaveric donors and live donors are only used for pediatric recipients. In 2011 was rule out a national program of split LT and this strategy became very important to palliate the shortage of livers for pediatric recipients [6]. Interestingly, Argentina is the country with the highest LT annual rate and LT access of the region. Probably this is a result of an aggressive policy of some group of accepting suboptimal liver grafts including fatty livers or liver from donor infected with endemic diseases such as Chagas seropositive infected donors [12–15]. The INCUCAI (Instituto Nacional Central Único Coordinador de Ablación e Implante) is the national organization responsible for the coordination of donation, procurement and transplantation activities. Its main responsibilities are the promotion of organ donation, setting the policies and bylaws, guidelines and recommendations for organ donation, procurement, allocation and transplantation. In addition INCUCAI manages the waiting lists, and follow-up registries. Argentina has developed in 2003 a national information system (SINTRA) to collect, filter, process, create and distribute data on donation and 5
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transplantation. Probably, as occurred in most countries of the region, the lack of financial support to improve the multi-organic donation rate is the main limitation for the development of the LT programs in the country. Bolivia: Although the first LT was performed more than 20 years ago (1996), the transplantation activity in Bolivia remains insufficient for the needs of the country. Unfortunately, the donation rate of deceased donor livers was zero in 2019 and only a few liver donor LTs were performed. Although the are some intents of improving transplantation law and donation policy to shift from informed to presumed consent, probably community education and cultural issues are responsible for the poor donation rate in Bolivia. Moreover, the access to LT in this country is critically low with only 0.3 LT annual rate PMP. Finally, we must state that the number of patients in the liver waiting list is low, and among them, the reported mortality in 2019 was 50%. Today, there is only 1 team preforming LT in two centers in Santa Cruz de la Sierra. The 4 live donors LT (1 adult-to-adult and 3 adult-topediatric) were performed with the assistance and collaboration of 2 north-American transplant surgeons traveling from the US. Paraguay: The first adult LT was performed in Hospital de Clínicas de Asunción (2015) and is the only active program in the country. In 4 years only 14 adult LT has been performed in Paraguay and thus, LT annual rate PMP is extremely low. Moreover, there is no active program of LT for children in the country. The donation rate is very low and recently, (2019) the country introduced the presumed consent for organ donation to improve transplantation access of the Population and reduce mortality on the waiting list. In contrast with the live donor kidney transplantation, there is no active live donor LT program to date. The is one single national list and the scarce livers are allocated using the MELD system. There are only a few patients listed for LT and the mortality rate on the waiting list is very high. However, the main problem is not the waiting list mortality, but the low access of patients to the national waiting list that was of only 6 patients at the end of 2019. Perú: In 1968 it was a first attempt to perform LT at an experimental level by V. Baracco's team. It was only at the beginning of this century that J. Chaman Ortiz set up the first transplant team in adults at the Guillermo Irigoyen Social Security Hospital in Lima, carrying out its first LT in 2000. The last modification of transplant law was in 2008 introducing the MELD allocation system and within the country, informed consent with family consultation is stablished for cadaveric donation. There is only one unique national list for patients under emergency status, but the allocation is regional. Mortality on the waiting list remains very high (30%) as a consequence low patient access to transplantation due to poor donation rate and very low LT annual rate in the country. Today Peru has 4 active LT teams (3 of them in the capital: Lima; 2 only adults, 1 only pediatric, and 1 adult and pediatric program). In 2016 Edgardo Rebaliati Social Security Hospital began the most important pediatric LT program in the country, and in 2019 Nacional Health Children's Institute performed the first LT in the public health system. Mexico. Mexico is the second most populated country in Latin America and the first LT was performed in 1985. Although public awareness regarding donation and transplantation has increased, unfortunately deceased organ donation and LT has been very low compared with other countries in the region being around 4.1 PMP and 1.5 PMP respectively (Table 1). Several efforts to increase donation and transplant activity has been done including the change to presumed consent for donation implemented in 2000. Despite this, change in donation and LT have been minimal and not enough for the needs of the country. According to national data, there are around. 30.000 deaths per year related to liver disease, however, there are less than 400 patients listed for liver transplantation per year and this number has not changed significantly over the last decade. There are many factors that contribute to the low access to LT.
university hospitals, 2 public hospitals, and 5 private clinics. They perform in total about 150 liver transplants per year with adequate post-LT outcomes. In Chile, the main limitation for LT is the low donation rate [17]. There is a national and unique liver waiting list. The prioritization system was changed in October 2011 to a MELD score system with a national exception committee. Unfortunately, this has not been able to decrease the dropout rate of 35–40% [18]. Since 2010, Chile introduced a presumed consent policy on organ donation, where all people over 18 years of age will be organ donors unless they state their negative. Although the idea was to increase the donation rate, there were problems with the implementation and the donation rate dropped. After a couple of modifications of the law, in terms of how to state their negative to donate, in 2019 they reinstalled the “hard” presumed consent, making the potential donor the only person that could have stated their negative during their lifetime. This last modification will be effective in September 2020, after which the family will not be consulted. Despite these efforts, the donation rate remains very low (between 7 and 10 PMP) and both the dropout and mortality rate on the waiting list remains very high. For this reason, in the most recent years, they have developed living donor LT for adult recipients, to reduce the mortality in the adult liver waiting list. At the Pontifical Catholic University of Chile, Nicolas Jarufe, Martin Dib and colleagues are performing over 10 adult-to-adult living donor liver transplant cases per year (about 20% of their LT activity), with equivalent graft and patient survival rates to cadaveric LT [4]. The benefits are seen not only in those recipients but on the national waiting list as it decreases the competition for the deceased organs. Regarding transplants in children, there are 3 well-established programs in Santiago and one in Concepción. Since 2011 at the UC transplant center, pediatric adult living donors are routinely performed by laparoscopy and have been progressively implemented in the other centers that perform pediatric transplants. Uruguay. Although in 1999 a team led by E. Torterolo in Uruguay performed the first liver transplant at the Armed Forces Hospital, this program was subsequently closed for many years. In 2009 M. Harguindeguy reinitiated a successful LT program who is the only available in Uruguay until today for adult patients. So far, there is no active pediatric LT program in Uruguay, every child is referred to Argentina. Allocation is based on MELD-Na system and mortality on the liver waiting list in 2019 was only 9% becoming one of the lowest of the region. Today, the donation rate in this country is over de median donation rate of the region (23.4 PMP) and donation after death is based on presumed consent with the familiar agreement. Live donation was developed neither for children nor for adults. Although the number of LT is continuously increasing, LT annual rate is only 7 PMP. To note, the only LT had excellent performance but there still many issues needing further development including better patient selection and surgical training in pediatric LT and live donation to increase accessibility to LT. Ecuador: Although the first anecdotic pediatric live donor LT was performed by a French team of surgeons in 2000, the development of an LT program in Ecuador took a few years more due to the lack of planning and economic support. Finally, in 2009, the first deceased donor adult LT was successfully performed in Ecuador by a local team. Today there are 5 active LT programs and, among all of them, they have performed only 30 LTs in 2019 with a very low LT annual rate. Probably, the low mortality in the waiting list reported in Ecuador reflects the low access to LT waiting list of the patients and not a high LT access as reported in other countries. The main limitation is the shortage of livers with a very low number of LTs performed in each center. Although the national donation rate is almost 5, only one-third of these donors were multi-organic being most of them mono-organic donors for deceased donor kidney 6
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also has audit duties and statistical at regional level. In 2019, the allocation criteria for LT in Colombia is moving from center-based towards patient-based allocation system (MELD, PELD). Emergency status liver transplant and children on the waiting list are priority. Today, Colombia is one of the countries with highest number of deceased donors LTs in the region with low mortality rate on the waiting list but LT access based on the LT annual rate is of only 5/ million. Certainly, in Colombia there are 81,000 annual cases of liver disease/year of which approximately 17,000 are cirrhotic and could need a LT. Currently, only 1.2% have access to a LT center. New laws are coming up since 2016 including the presumed consent form, and some other laws that guarantee the balance in organ allocation and financial support. Now all people are organ donors in a case of brain death, unless they have registered their refusal/negation in a national registry; This new policy at the very beginning, increased the annual donation rate in 2017 to 19.9/million, nevertheless soon after annual donation rate dropped to 8.2 in 2019/million. During 2019, only 259 LTs were performed in Colombia, of which 52 were from a living donor (50 pediatric – 2 adults).
México has a complex healthcare system with several subsystems that covered different sectors of the population; Each subsystem has their own hospitals network and there is little communication among the subsystems, therefore access to LT depends on the activity of LT within each subsystem, being Notable different. The significant low number of patients listed for LT, exposed the difficulties of access to high quality health care regardless which subsystem the patients belongs. There has been an increase activity of LT in the private sector, however, it is estimated that less than 6% of the population has private insurance. In addition, there is a complex legal framework regarding organ donation and transplantation. In order to do an organ procurement, the hospital requires a special license that most of the hospitals in the country don't have. If there is a potential donor in a non-licensed hospital, arranges have to be done to transfer the potential donor to a licensed facility which is a negative incentive for donation. Besides this, there are 80 centers authorized to perform a LT, however, less that 5% of them perform 10 LT or more per year and more than 70% remain inactive. In addition, according to the Mexican law, the committee of the center that has an organ donor decides how to allocate the organs, first within their own health subsystem and then to others, however, there are not national or regional lists based on MELD, limiting the capacity of the donor center to allocate the organ based on how sick the patients are. Therefore, every hospital that has an active LT program has their own waiting list and when an organ is allocated to the center, their own committee decides how to allocate the liver. An exception to this has been a recent system put in place by CENATRA (the national organization responsible for the coordination of donation, procurement and transplantation activities) to expedite communication among all the centers in the country to facilitate organ allocation for patients categorized as a national urgency. Besides all these barriers and limitations important achievements have been done including, Domino liver transplantation, combined Liver-Kidney, Liver-Heart and Liver- Bone Marrow transplantation and Living donor liver transplantation in children and adults among others, however there are many areas or opportunities in all the process from the detection of a potential donor to the organ allocation that will likely increase the LT activity [19,20]. Colombia: The first LT in this country was performed at the San Vicente de Paul Hospital (Medellin) in 1979 by A. Velásquez. In 1988 the Fundación Santa Fe de Bogotá Hospital, started the LT program with a team trained by Paul McMaster at the Queen Elizabeth Hospital – Birmingham UK. The first successful LT at this hospital was performed by G. Quintero in 1988, followed by the first successful pediatric LT with a divided organ in 1991. Currently the longest survival after a LT is 30 years, this patient is doing well and active. In 1996 Fundación Valle de Lili (Cali) began also a LT program. Since then more than 3100 liver transplants have been performed in Colombia. Currently there are 9 centers performing liver transplants in Colombia of which 4 centers: Fundación Santa Fe de Bogotá, Valle de Lili Foundation (Cali), Cardioinfantil foundation (Bogotá) and Pablo Tobon Uribe Hospital (Medellin) perform this procedure in pediatric population. At the beginning, LT in Colombia relied on isolated efforts from few private hospitals with heroic medical teams. No transplant network or governmental support was in place then and the surgical practice was interrupted repeatedly. Since 2004, an organ transplant donation network was established at two different levels. At a National level, the National Institute of Heath (INS) plays a role in data collection, data analysis, auditing organ donation, transplant activity. and also processes along the transplant network to achieve balanced organ allocation. Transplant activity rules and interaction between centers are also tasks of this Institute. National waiting list is managed by the institute and fed by every transplant team. At a regional level, there are 6 regions in Colombia that undependably organizes local transplant activity, coordinates organ donors detection, donor maintenance and organ and tissue retrieval. It
3. Final considerations More than 2500 procedures are performed in the region every year; A recent multicenter cohort study in Latin-America of patients transplanted for HCC demonstrated that chronic HCV was the main etiology in the overall cohort (36.6%), followed by HBV (25.3%), alcoholic liver disease (16.8%), cryptogenic cirrhosis (7.4%) and non-alcoholic fatty liver disease (5.7%). This observation showed that there might be a changing figure regarding etiologies of HCC similar to What has been reported in other regions of the world, including a decreasing proportion of HCV and an increasing proportion of NAFLD. From years 2005–2012, viral related transplanted HCC (HCV + HBV) decreased from 66% to 50%. Although chronic hepatitis C infection was the leading cause of HCC in the region, high number of HBV related HCC was observed, particularly from Brazil, Argentina and Colombia [2]. As occurred worldwide, the number of patients on liver waiting lists in Latin America grows disproportionately compared to the number of transplants performed. Although many law modifications have been made in the last year, most countries lack social awareness about the importance of donation and the irreversibility of the brain death. The mechanisms and norms for organ procurement and infrastructure development, capable of supporting this high demand, are still in slow progress in some countries. Moreover, it must also be considered that family acceptance varies greatly in the regions of Latin America, despite the intent to implement a “hard” presumed consent in a few countries. Regarding organ donation, each country needs to work on developing strategies to educate the community, lower the refusal of family members and overcoming logistical and operational problems to improve donation rates. Access to LT in the region is very heterogeneous. While some countries have no active LT programs, others as Brazil have the largest public transplantation system in the world. While some countries have only a few LT centers, others have too many LT centers performing an inadequate number of LTs. Further investigations focused on the strict analysis of specific variables including cultural, logistic and socio-economic factors inherent to each country individually would be interesting in the future to understand and improve LT access, transplant laws and allocation rules. Disparity to access to transplantation remain the major challenge in the region. Organ donation and LT should be performed by limited centers with the human and material resources needed to succeed along with the financial and government support on a legal framework that favors equality and justice for the patients. Cultural and educational efforts have to be accompanied with transparent public policies that will likely increase organ donation and activity in transplantation. 7
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References
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8
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.elsevier.com/locate/ijsu
Current status of liver transplantation in Latin America Alan G. Contrerasa,∗, Lucas McCormackb, Wellington Andrausc, Eduardo de Souza M Fernandesd, on behalf of the Latin America Liver Transplantation Group (Alan G. Contrerase, Lucas McCormackf, Wellington Andrausg, Eduardo de Souza M. Fernandesg, Alejandro Serrablo Requejoh, Nicolás Jarufei, Martin Dibi, Felix Carrascoj, Martin Harguindeguyk, Jose Pablo Garbanzol, Frans Serpam, Alejandro Gimenezn, Ricardo Villaroelo, Alonso Verap) a
Department of Surgery, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico Department of Surgery, Hospital Aleman, Buenos Aires, Argentina Digestive Organs Transplant Division, Gastroenterology Department, Sao Paulo University School of Medicine, Sao Paulo, Brazil d Department of Surgery, Rio de Janeiro Federal University, Department of Surgery and Abdominal Organ Transplant, São Lucas Hospital, Copacabana, Brazil e Mexico f Argentina g Brazil h Spain i Chile j Peru k Uruguay l Costa Rica m Ecuador n Paraguay o Bolivia p Colombia b c
A R T I C LE I N FO
A B S T R A C T
Keywords: Liver transplantation Latin America
The lack of adequate financial coverage, education, and the organization has been the main limiting factor for the development of transplantation in Latin America. As occurred worldwide, the number of patients on liver waiting lists in Latin America grows disproportionately compared to the number of liver transplantations (LTs) performed. Although many law modifications have been made in the last year, most countries lack social awareness about the importance of donation and the irreversibility of brain death. The mechanisms and norms for organ procurement and infrastructure development, capable of supporting this high demand, are still in slow progress in most countries. Access to LT in the region is very heterogeneous. While some countries have no active LT programs so far, others are an international model of a public transplantation system (Brazil) or a national information system (Argentina). While some countries have only a few LT centers, others have too many LT centers performing an inadequate low number of LTs. Disparity to access transplantation remains the major challenge in the region. Cultural and educational efforts have to be accompanied by transparent public policies that will likely increase organ donation and activity in transplantation. The purpose of this article is to review the trends and current activity in LT within Latin America, based on prior publications and the information available in each country of the region.
1. Introduction Surgery in Latin America was developed with the influence of European and North American schools of surgery. In the 1970s and 80s,
many surgeons from the region were trained at centers of liver transplantation (LT) in North America and Europe, returning to their native countries to set up their units of transplantation. However, the lack of adequate financial coverage, education, and organization has been the
∗ Corresponding author. Department of Surgery, Transplant Division, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez Secc 16, Tlalpan, 14080, Ciudad de México, CDMX, Mexico E-mail address: [email protected] (A.G. Contreras).
https://doi.org/10.1016/j.ijsu.2020.03.039 Received 6 February 2020; Received in revised form 6 March 2020; Accepted 18 March 2020 1743-9191/ © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Alan G. Contreras, et al., International Journal of Surgery, https://doi.org/10.1016/j.ijsu.2020.03.039
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2. How is liver allocation in Latin America?
Abbreviations
Organ allocation systems have been developed to distribute organs more equitably based on the fact that there are not enough donated organs to transplant everyone in need. The scarcity of organs for LT in Latin America is the most important factor leading to the deaths of patients on waiting lists. The need for liver transplantation is different due to the differences in the epidemiology of liver disease and the organization of health care [1,2]; some countries have a disproportionated low number of patients in the waiting list exposing other important factors including a disproportionated access to high quality health care. Therefore, the equitable allocation of donated organs to patients who need them the most on the waiting list is crucial. Liver allocation policy in most countries of Latin America was initially based on a patient's location of care and time on the waiting list. The social and political requests for a better allocation system focusing on the patient's severity of underlying liver disease led to the implementation of the allocation policy based on the model for end-stage liver disease (MELD score) in some countries of the region (Table 1). In 2005, Argentina was the first country after the US to adopt the MELD system for LT. Implementation of the MELD scoring system improved organ allocation but, unfortunately, this new policy has no change the waiting list mortality [3]. Socio-economic factors and differences between the US and Latin American countries’ health systems may explain why patient survival on some Latin American waiting list was no significantly improved after MELD. Despite different organ allocation systems across Latin America, the principles of utility and justice remain, however, there is still a lag in the evolution of public policies regarding organ allocation and transplantation, for instance, some countries have predominantly center-based allocation system. (e.g. Mexico), whereas most have moved toward recipient-based systems utilizing MELD or MELD-Na for the allocation. As expected, the critiques argue that MELD score may not sufficiently prioritize certain patient populations and give an unfair benefit to other subpopulations [3]. However, the only way to ameliorate the conflict between utility and justice is by increasing the supply of donor organs. An analysis of specific variables including cultural, logistic and socio-economic factors would potentially help in optimizing these principles in each country individually.
LT DCD
liver transplantation donation after circulatory death LDLT = Living donor liver transplantation PMP= Per Million of Population MELD Model for end-stage liver disease MELD-Na Model for end-stage liver disease- Sodium HCV= Hepatitis C Virus HBV Hepatitis B Virus NAFLD Nonalcoholic fatty liver disease HCC= Hepatocellular Carcinoma
main limiting factors for the development of liver surgery and transplantation in Latin America. When compared with Europe or the US, in Latin America the donation rate is dramatically lower (Fig. 1). Additionally, the activity in LT is very different throughout all the Latin American countries whereas countries like Argentine and Brazil perform more than 10 LT per million of population (PMP) and countries like Venezuela, Dominican Republic, Paraguay and Bolivia around 0.2 to 0.4 PMP. Moreover, LT is not performed in 7 countries of Central America including Guatemala, Trinidad y Tobago, Honduras, Nicaragua, Panama, El Salvador, and Haiti. Among the countries with active LT programs in Latin America, pediatric live donor LT programs have been performed in only 7 countries and only in 4 for adults with the intention to palliate the organ shortage and mortality on waiting lists (Table 1). In 2019, Brazil, Chile, México and Colombia were the only countries performing a live donor adult-to-adult LT among the region. To date, no team in the region have developed a Donor after Circulatory Death (DCD) LT program to palliate donor shortage. There are not supplementary incentives for deceased or living donors in the region and organ trafficking is prohibited and punished by law in Latin America. The purpose of this article is to review the trends and current activity in LT within Latin America, based on prior publications and the information available in each country of the region. To note, data regarding current LT activity in the Dominican Republic, Cuba and Venezuela were not available for the authors of this article. As transplant services available in Puerto Rico comply with federal rules and standards under the Organ Procurement and Transplantation Network/ United Network for Organ Sharing, its information was not included in this article.
Fig. 1. Annual Deceased Donor Organ Rate in 2019 among countries of the region (PMP: Per Million Population). 2
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Table 1 Statistics referred to each Latin American country with active centers performing liver transplantation in 2019. They are listed by number of transplants performed during 2019.
Brazil Argentine México Chile Colombia Perú Ecuador Uruguay Costa Rica Paraguay Bolivia
Population (millons)
Initiation of LT
LT centers
Donation rate (PMP)
LT annual rate (PMP)
DDLTs
Pediatric LDLTs
Adult LDLTs
210.1 43.4 127 17.9 48.2 32.5 16.1 3.4 4.8 7.2 11
1968 1988 1985 1985 1979 2000 2000 1998, 2009 1993 2015 1996
60 33 80 9 9 4 5 1 3 1 2
17.7 19.6 4.1 10.4 8.2 2.3 4.9 23.4 (2018) 4.7 5.7 1.1
10.4 10.8 1.5 9.1 5 1.6 1.8 7 3.9 0.3 0.3
2006 429 213 145 207 46 30 24 19 2 0
136 42 8 6 50 6 0 0 0 0 3
22 0 2 12 2 0 0 0 0 0 1
LT: Liver Transplantation; DDLT: Deceased Donor Liver Transplantation; LDLT: Live Donor Liver Transplantation; PMP: per million population; N/A: Not Available.
Other methods to increase the liver transplant rates include the development of active split liver programs (e.g. Argentina), domino transplantation, live donation program and, today, active utilization of donation after cardiac death donors that has not been applied in the region for LT [6].
2.1. Is the supply of deceased donor organs adequate? Organ donation in Latin America The donation rate in Latin America had a continuous increment throughout the last decade [4], however, it has been quite different among the countries. The supply of deceased donor organs varies according to the legal framework for donation and the population's attitude toward organ donation, and the interest and organization of the health care system regarding transplantation. Many countries had a donation rate above the average such as Uruguay, Argentina, and Brazil (Table 1). Unfortunately, a high rate of refusal to donate is still a major obstacle. For example in Brazil, the largest country of the region, of all federative units in Brazil, in 13 states the refusal rate exceeded 50%, reaching 80% in Mato Grosso and 74% in Sergip [5]. Probably, the surrogate factor is the lack of knowledge to understand that brain death is a situation of absolute irreversibility and not a reversible coma. Another area of opportunity is to increase the utilization of organs from potential donors that are not identified nor reported. In this sense, public policies should be in place to incentivize hospitals and health care providers to see this as opportunity of life for other patients and a legal framework and a system in place should facilitate the process. This could be a potential source of donors that are discarded in good condition. Additionally, once the donor is identified, several factors might influence the success of the multi-organic procurement such as inaccurate clinical evaluation of the potential donor; improper body maintenance; delays due to distance and accessibility by the organ removal teams; technical problems at the retrieval operation, problems with the organ mobilization or packing conditions; long cold ischemia time, among others, and they all should be taken into consideration as potential areas of opportunity to increase the utilization of organs.
2.2. Legislation for organ donation and transplantation Many important legal issues have been clearly documented in the transplantation laws of most Latin American countries including brain death diagnosis criteria, the type of consent for retrieval, the concept of altruistic living related donation, restrictions for living unrelated donation, medical criteria for allocation and a clear prohibition of organ commercialization [4]. Creating a presumed donor law was a move many countries have made trying to solve the organ donor crisis that affects the region. With this, unless the deceased person had left explicit instructions, relatives were given the final decision regarding organ donation. In other words, as established in the Spanish model, the families of each organ donor are consulted systematically before donation proceeds and they must give their final consent for organ donation. However, family refusal is the most important limitation of cadaveric donation once the donation process has been initiated. As a reaction to this difficult scenario, a “hard” presumed donor law aiming to drastically reduce the waiting time for those needing a transplant and hoping to reduce mortality on the waiting list has been implemented recently in Argentine. Today in Argentine, all adults over 18 are organ donors unless they expressly indicate otherwise before death, regardless of the familiar opinion. Interestingly, after the implementation of the so-called “Justina Law” in Argentina, in honor to a pediatric patient who died on
Table 2 Allocation policy, legislation and waiting list variables in each Latin American country in 2019. Consent for donation. Law modification (Year)
Family consultation
Allocation system
Waiting list (national/regional)
Mortality liver WL (%)
Argentine
Presumed consent (2005). (2019)
NO
National. Unique
16.2
Brazil Chile
Presumed consent (2006) Presumed consent (2019)
YES YES/NO
Regional National. Unique
N/A 29.6
Perú
Informed consent (2008)
YES
Presumed consent (2009) Presumed consent (2000) Presumed consent (2014) Presumed consent (2013) Presumed consent (2019. Ley Anita) Informed consent (1996) Presumed consent (2004, 2016)
YES YES YES YES NO YES YES
NationalUnique (regional for emergency) National (only adults) Unique. Center-oriented National National National National Regional
30
Uruguay México Costa Rica Ecuador Paraguay Bolivia Colombia
MELD- Na National exception committee MELD MELD- Na National exception committee MELD National exception committee MELD- Na Exception rules Center-oriented MELD-Na MELD MELD MELD Center-oriented/MELD
N/A: Not Available. 3
9 N/A N/A 8% 33% 50% 5,7
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on the waiting list are disproportionately low. Unfortunately, in many regions, educational, geographical, cultural and financial barriers along with different access to high Quality health care are limiting the access of cirrhotic patients to active LT programs and many patients needing a LT are dying outside the waiting list. We must state that the region is very heterogeneous and some issues regarding LT access, legislation and allocation need specific discussion for each country. Although LT activity was initiated many years ago in a few countries including Cuba (1986). Dominican Republic (2007) and Venezuela (1989) according to the STALYC report, the data regarding access to LT in 2019 was not available at the time of this review [4]. Brazil: The first LT was performed in 1968, the first successful LT (1985) and also the first live donor LT (1988) were performed by the team of the Liver Unit of the São Paulo Medical School, São Paulo University. Brazil is the largest country in Latin America, the second in number of liver transplants in the Western world and the first in Latin America. In 2019, more than 2000 deceased donor LT were performed being the highest number of LTs in the region, however because of the big population, the rate per million of population is only 10.4, and the total estimated need number of LT is 5500 per year, leading to a big waiting list and a high wait list mortality. Development of live donor LT (LDLT) for children and adults is the largest of the region (Table), on the other hand, while the number of deceased donors and deceased donor liver transplant (DDLT) keep growing year by year, LDLT number has been stable for many years and count for around only 8% of the total number of LTs [8]. Nowadays, Brazil is pioneering in the region the inclusion of novel indications for LT such as intra-hepatica cholangiocarcinoma and unresectable colorectal liver metastases fulfilling very strict criteria. As these are experimental indications so far, DDLT is not possible due to organ shortage problem and living donor liver transplant (LDLT) seems to be the only available alternative in Brazil. The first report of patient with colorectal liver metastases who underwent LDLT in Latin America was recently performed in Rio de Janeiro [9]. As a consequence of the big geographical area, an important regional disparity within the country challenge the equal access for LT of the population. Some regions are thousands of kilometers from LT centers. In Brazil, LT is only available in just 14 of the 26 states. The patients are listed in regionals waiting lists, each state that has
the cardiac waiting list, a similar scenario motivated legislators in Paraguay to recently also implement the so-called “Anita Law”, honoring to another patient who died waiting for a heart in Asunción. Although a significant increment in donation rate has occurred in Argentina reaching a record an annual donate rate of 19.6 PMP in 2019, its impact on the Paraguay donation rate was not positive so far. As a cascade effect, Chile has decided to introduce also the “hard” consent policy in the following months of 2020. Adequate legislation in each country is crucial to improve organ donation. In the region, the “presumed consent” countries have higher donation rates (Tables 1 and 2), however it is important to acknowledge that this might be a reflection of the interest of the population and legislators in those countries to increase organ donation and transplantation activity. Others have shown that places where the decision of donation is left to the donors (Opt-In) has better results than presumed consent (Opt-out) probably due to prioritizing of individual autonomy in a rights-based culture [7]. Legislation has to go further than Opt-in or Opt-out policies and a complete legal framework in the entire process including the detection of potential donors and expedite legal steps to allow donation, the organ harvesting, organ allocation and transportation and finally the practice of regulated and supported transplant centers will increase transparency, donation and transplant activity. 2.3. Access to liver transplantation and mortality on waiting list The number of LT performed in Latin America has grown constantly over the last years being Brazil the largest country in numbers of LT performed in 2019 (Fig. 2). However, there is an important gap between the donation rate and the LT annual rate probably due to the fact than most procurements are only performed for kidney transplantation (Fig. 3). The underlying problem is maybe poor donor maintenance, an excessive number of suboptimal donors or an inadequate infrastructure to organize multi-organic procurement due to logistic or geographical difficulties. Mortality in the LT waiting list varies among the regions being very high in countries such as Chile, Peru, Paraguay and Bolivia. This situation forced the groups of Chile to develop Adult-to-Adult LT programs in the country to improve access to LT. However, the mortality on the waiting list alone is not a good marker of access to LT in the region and might underestimate the mortality of patients that could potentially benefit of liver transplantation in countries where patients
Fig. 2. Annual Deceased Liver Transplantation rate in 2019 among countries of the region. 4
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Fig. 3. Deceased Donor Liver Transplantation performed in 2019 among countries of the region.
transplantation activities. This tool allows transparency, traceability and quality of procedures and is a model of the region. Donation and transplantation costs are funded by the health care system. Public or private health care institutions must be accredited for retrieval and transplantation, and health care professionals must be certified. Brain death must be certified by whole brain death criteria according to law. Presumed consent is the current legal requirement for donation from deceased donors. Law only allows organ donation from living related donors. In 2005, Argentina introduced a “soft” presumed consent policy for organ donation, where all people over 18 years of age will be organ donors unless they or their family state their negative. In 2019, a new law passed removing the family consent for organ donation (so-called “hard” presumed consent). This policy makes the potential donor “alive” the only person that can state their negative. Argentina's National Institute for the Coordination of Ablation and Implantation (INCUCAI) has informed that after the implementation of the new transplantation law in 2019, a significant increment in donation rate has occurred. However, the removal of the family consent after donor death is a controversial issue that remains under discussion within the transplant community. All patients are listed in a “unique national” waiting list, and thus, there is no allocation of organs from deceased donors to regional or LTcenters. On liver WL there are two major categories: emergency and elective candidates. Emergency status receives top priority on the WL all LT elective candidates listed in Argentina were re-categorized using the MELD score for organ allocation since 2005 [3]. When the MELD score may not estimate the severity of illness, each center can request a National Experts Committee for additional “priority” points [16]. Medical conditions that qualify for additional MELD points include familial amyloidotic polyneuropathy (16 points), hepatopulmonary syndrome (20 points) and T2 stage hepatocellular carcinoma. Each center can also request additional points for other conditions that diminish quantity or quality of life but are not included in the MELD score. Unfortunately, due to MELD system limitations, the extra-MELD points are frequently requested being today more than 50% of the LTs performed in the country based on extra-MELD points [16]. Chile: The first adult liver transplant in Chile occurred in 1969, although the patient passed at the end of the intervention. The first successful liver transplant was performed in 1985 at the Military Hospital of Santiago de Chile by Juan Hepp. The first successful pediatric transplant with a living related donor was performed in 1999 by Erwin Buckel and colleagues at Las Condes Clinic, in the same city. Currently, there are 9 active centers for LT in Chile, including 2
transplant centers has its own waiting list. São Paulo has the biggest population, 45 million people, and with the biggest waiting list, thus it is the only state with two regionals, the capital plus the coast and the countryside. In 1998, following some other countries worldwide, Brazil also tried a presumed consent for organ donation, where everybody was donor unless the person registered “NO” in his ID. Unfortunately this step resulted in a negative impact in organ donation, and three years later the National Transplant System came back to the family consent that is still working today. The Associação Brasileira de Transplante de Órgãos – Brazilian Association of Organ Transplantation, is the source of Brazilian statistical data [10]. According to the most recent report, in 2019 the country reached a rate of 17.7 donors PMP, and two states of Brazil had more than 40 donors PMP, showing a big potential for the country. Argentine. In 1988, de Santibañes at the Hospital Italiano of Buenos Aires carried out the first adult LT in Argentine. This team was a pioneer in the region, by also performing other procedures including pediatrics LT, split LT for children (1992), a live donor in a pediatric (1992) and an adult patient (1998) [11]. This team contributed to surgical education in the HPB field developing the first fellowship program in the region (1992) and collaborated in training surgeons not only in Argentina but also in neighboring countries. Today there are 33 active LT programs in Argentina being the vast majority in Buenos Aires. Unfortunately, as a result of the low donation rate, many LT programs have performed less than 10 transplants per year in the country in 2019. Today, most LTs are performed from cadaveric donors and live donors are only used for pediatric recipients. In 2011 was rule out a national program of split LT and this strategy became very important to palliate the shortage of livers for pediatric recipients [6]. Interestingly, Argentina is the country with the highest LT annual rate and LT access of the region. Probably this is a result of an aggressive policy of some group of accepting suboptimal liver grafts including fatty livers or liver from donor infected with endemic diseases such as Chagas seropositive infected donors [12–15]. The INCUCAI (Instituto Nacional Central Único Coordinador de Ablación e Implante) is the national organization responsible for the coordination of donation, procurement and transplantation activities. Its main responsibilities are the promotion of organ donation, setting the policies and bylaws, guidelines and recommendations for organ donation, procurement, allocation and transplantation. In addition INCUCAI manages the waiting lists, and follow-up registries. Argentina has developed in 2003 a national information system (SINTRA) to collect, filter, process, create and distribute data on donation and 5
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transplantation. Probably, as occurred in most countries of the region, the lack of financial support to improve the multi-organic donation rate is the main limitation for the development of the LT programs in the country. Bolivia: Although the first LT was performed more than 20 years ago (1996), the transplantation activity in Bolivia remains insufficient for the needs of the country. Unfortunately, the donation rate of deceased donor livers was zero in 2019 and only a few liver donor LTs were performed. Although the are some intents of improving transplantation law and donation policy to shift from informed to presumed consent, probably community education and cultural issues are responsible for the poor donation rate in Bolivia. Moreover, the access to LT in this country is critically low with only 0.3 LT annual rate PMP. Finally, we must state that the number of patients in the liver waiting list is low, and among them, the reported mortality in 2019 was 50%. Today, there is only 1 team preforming LT in two centers in Santa Cruz de la Sierra. The 4 live donors LT (1 adult-to-adult and 3 adult-topediatric) were performed with the assistance and collaboration of 2 north-American transplant surgeons traveling from the US. Paraguay: The first adult LT was performed in Hospital de Clínicas de Asunción (2015) and is the only active program in the country. In 4 years only 14 adult LT has been performed in Paraguay and thus, LT annual rate PMP is extremely low. Moreover, there is no active program of LT for children in the country. The donation rate is very low and recently, (2019) the country introduced the presumed consent for organ donation to improve transplantation access of the Population and reduce mortality on the waiting list. In contrast with the live donor kidney transplantation, there is no active live donor LT program to date. The is one single national list and the scarce livers are allocated using the MELD system. There are only a few patients listed for LT and the mortality rate on the waiting list is very high. However, the main problem is not the waiting list mortality, but the low access of patients to the national waiting list that was of only 6 patients at the end of 2019. Perú: In 1968 it was a first attempt to perform LT at an experimental level by V. Baracco's team. It was only at the beginning of this century that J. Chaman Ortiz set up the first transplant team in adults at the Guillermo Irigoyen Social Security Hospital in Lima, carrying out its first LT in 2000. The last modification of transplant law was in 2008 introducing the MELD allocation system and within the country, informed consent with family consultation is stablished for cadaveric donation. There is only one unique national list for patients under emergency status, but the allocation is regional. Mortality on the waiting list remains very high (30%) as a consequence low patient access to transplantation due to poor donation rate and very low LT annual rate in the country. Today Peru has 4 active LT teams (3 of them in the capital: Lima; 2 only adults, 1 only pediatric, and 1 adult and pediatric program). In 2016 Edgardo Rebaliati Social Security Hospital began the most important pediatric LT program in the country, and in 2019 Nacional Health Children's Institute performed the first LT in the public health system. Mexico. Mexico is the second most populated country in Latin America and the first LT was performed in 1985. Although public awareness regarding donation and transplantation has increased, unfortunately deceased organ donation and LT has been very low compared with other countries in the region being around 4.1 PMP and 1.5 PMP respectively (Table 1). Several efforts to increase donation and transplant activity has been done including the change to presumed consent for donation implemented in 2000. Despite this, change in donation and LT have been minimal and not enough for the needs of the country. According to national data, there are around. 30.000 deaths per year related to liver disease, however, there are less than 400 patients listed for liver transplantation per year and this number has not changed significantly over the last decade. There are many factors that contribute to the low access to LT.
university hospitals, 2 public hospitals, and 5 private clinics. They perform in total about 150 liver transplants per year with adequate post-LT outcomes. In Chile, the main limitation for LT is the low donation rate [17]. There is a national and unique liver waiting list. The prioritization system was changed in October 2011 to a MELD score system with a national exception committee. Unfortunately, this has not been able to decrease the dropout rate of 35–40% [18]. Since 2010, Chile introduced a presumed consent policy on organ donation, where all people over 18 years of age will be organ donors unless they state their negative. Although the idea was to increase the donation rate, there were problems with the implementation and the donation rate dropped. After a couple of modifications of the law, in terms of how to state their negative to donate, in 2019 they reinstalled the “hard” presumed consent, making the potential donor the only person that could have stated their negative during their lifetime. This last modification will be effective in September 2020, after which the family will not be consulted. Despite these efforts, the donation rate remains very low (between 7 and 10 PMP) and both the dropout and mortality rate on the waiting list remains very high. For this reason, in the most recent years, they have developed living donor LT for adult recipients, to reduce the mortality in the adult liver waiting list. At the Pontifical Catholic University of Chile, Nicolas Jarufe, Martin Dib and colleagues are performing over 10 adult-to-adult living donor liver transplant cases per year (about 20% of their LT activity), with equivalent graft and patient survival rates to cadaveric LT [4]. The benefits are seen not only in those recipients but on the national waiting list as it decreases the competition for the deceased organs. Regarding transplants in children, there are 3 well-established programs in Santiago and one in Concepción. Since 2011 at the UC transplant center, pediatric adult living donors are routinely performed by laparoscopy and have been progressively implemented in the other centers that perform pediatric transplants. Uruguay. Although in 1999 a team led by E. Torterolo in Uruguay performed the first liver transplant at the Armed Forces Hospital, this program was subsequently closed for many years. In 2009 M. Harguindeguy reinitiated a successful LT program who is the only available in Uruguay until today for adult patients. So far, there is no active pediatric LT program in Uruguay, every child is referred to Argentina. Allocation is based on MELD-Na system and mortality on the liver waiting list in 2019 was only 9% becoming one of the lowest of the region. Today, the donation rate in this country is over de median donation rate of the region (23.4 PMP) and donation after death is based on presumed consent with the familiar agreement. Live donation was developed neither for children nor for adults. Although the number of LT is continuously increasing, LT annual rate is only 7 PMP. To note, the only LT had excellent performance but there still many issues needing further development including better patient selection and surgical training in pediatric LT and live donation to increase accessibility to LT. Ecuador: Although the first anecdotic pediatric live donor LT was performed by a French team of surgeons in 2000, the development of an LT program in Ecuador took a few years more due to the lack of planning and economic support. Finally, in 2009, the first deceased donor adult LT was successfully performed in Ecuador by a local team. Today there are 5 active LT programs and, among all of them, they have performed only 30 LTs in 2019 with a very low LT annual rate. Probably, the low mortality in the waiting list reported in Ecuador reflects the low access to LT waiting list of the patients and not a high LT access as reported in other countries. The main limitation is the shortage of livers with a very low number of LTs performed in each center. Although the national donation rate is almost 5, only one-third of these donors were multi-organic being most of them mono-organic donors for deceased donor kidney 6
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also has audit duties and statistical at regional level. In 2019, the allocation criteria for LT in Colombia is moving from center-based towards patient-based allocation system (MELD, PELD). Emergency status liver transplant and children on the waiting list are priority. Today, Colombia is one of the countries with highest number of deceased donors LTs in the region with low mortality rate on the waiting list but LT access based on the LT annual rate is of only 5/ million. Certainly, in Colombia there are 81,000 annual cases of liver disease/year of which approximately 17,000 are cirrhotic and could need a LT. Currently, only 1.2% have access to a LT center. New laws are coming up since 2016 including the presumed consent form, and some other laws that guarantee the balance in organ allocation and financial support. Now all people are organ donors in a case of brain death, unless they have registered their refusal/negation in a national registry; This new policy at the very beginning, increased the annual donation rate in 2017 to 19.9/million, nevertheless soon after annual donation rate dropped to 8.2 in 2019/million. During 2019, only 259 LTs were performed in Colombia, of which 52 were from a living donor (50 pediatric – 2 adults).
México has a complex healthcare system with several subsystems that covered different sectors of the population; Each subsystem has their own hospitals network and there is little communication among the subsystems, therefore access to LT depends on the activity of LT within each subsystem, being Notable different. The significant low number of patients listed for LT, exposed the difficulties of access to high quality health care regardless which subsystem the patients belongs. There has been an increase activity of LT in the private sector, however, it is estimated that less than 6% of the population has private insurance. In addition, there is a complex legal framework regarding organ donation and transplantation. In order to do an organ procurement, the hospital requires a special license that most of the hospitals in the country don't have. If there is a potential donor in a non-licensed hospital, arranges have to be done to transfer the potential donor to a licensed facility which is a negative incentive for donation. Besides this, there are 80 centers authorized to perform a LT, however, less that 5% of them perform 10 LT or more per year and more than 70% remain inactive. In addition, according to the Mexican law, the committee of the center that has an organ donor decides how to allocate the organs, first within their own health subsystem and then to others, however, there are not national or regional lists based on MELD, limiting the capacity of the donor center to allocate the organ based on how sick the patients are. Therefore, every hospital that has an active LT program has their own waiting list and when an organ is allocated to the center, their own committee decides how to allocate the liver. An exception to this has been a recent system put in place by CENATRA (the national organization responsible for the coordination of donation, procurement and transplantation activities) to expedite communication among all the centers in the country to facilitate organ allocation for patients categorized as a national urgency. Besides all these barriers and limitations important achievements have been done including, Domino liver transplantation, combined Liver-Kidney, Liver-Heart and Liver- Bone Marrow transplantation and Living donor liver transplantation in children and adults among others, however there are many areas or opportunities in all the process from the detection of a potential donor to the organ allocation that will likely increase the LT activity [19,20]. Colombia: The first LT in this country was performed at the San Vicente de Paul Hospital (Medellin) in 1979 by A. Velásquez. In 1988 the Fundación Santa Fe de Bogotá Hospital, started the LT program with a team trained by Paul McMaster at the Queen Elizabeth Hospital – Birmingham UK. The first successful LT at this hospital was performed by G. Quintero in 1988, followed by the first successful pediatric LT with a divided organ in 1991. Currently the longest survival after a LT is 30 years, this patient is doing well and active. In 1996 Fundación Valle de Lili (Cali) began also a LT program. Since then more than 3100 liver transplants have been performed in Colombia. Currently there are 9 centers performing liver transplants in Colombia of which 4 centers: Fundación Santa Fe de Bogotá, Valle de Lili Foundation (Cali), Cardioinfantil foundation (Bogotá) and Pablo Tobon Uribe Hospital (Medellin) perform this procedure in pediatric population. At the beginning, LT in Colombia relied on isolated efforts from few private hospitals with heroic medical teams. No transplant network or governmental support was in place then and the surgical practice was interrupted repeatedly. Since 2004, an organ transplant donation network was established at two different levels. At a National level, the National Institute of Heath (INS) plays a role in data collection, data analysis, auditing organ donation, transplant activity. and also processes along the transplant network to achieve balanced organ allocation. Transplant activity rules and interaction between centers are also tasks of this Institute. National waiting list is managed by the institute and fed by every transplant team. At a regional level, there are 6 regions in Colombia that undependably organizes local transplant activity, coordinates organ donors detection, donor maintenance and organ and tissue retrieval. It
3. Final considerations More than 2500 procedures are performed in the region every year; A recent multicenter cohort study in Latin-America of patients transplanted for HCC demonstrated that chronic HCV was the main etiology in the overall cohort (36.6%), followed by HBV (25.3%), alcoholic liver disease (16.8%), cryptogenic cirrhosis (7.4%) and non-alcoholic fatty liver disease (5.7%). This observation showed that there might be a changing figure regarding etiologies of HCC similar to What has been reported in other regions of the world, including a decreasing proportion of HCV and an increasing proportion of NAFLD. From years 2005–2012, viral related transplanted HCC (HCV + HBV) decreased from 66% to 50%. Although chronic hepatitis C infection was the leading cause of HCC in the region, high number of HBV related HCC was observed, particularly from Brazil, Argentina and Colombia [2]. As occurred worldwide, the number of patients on liver waiting lists in Latin America grows disproportionately compared to the number of transplants performed. Although many law modifications have been made in the last year, most countries lack social awareness about the importance of donation and the irreversibility of the brain death. The mechanisms and norms for organ procurement and infrastructure development, capable of supporting this high demand, are still in slow progress in some countries. Moreover, it must also be considered that family acceptance varies greatly in the regions of Latin America, despite the intent to implement a “hard” presumed consent in a few countries. Regarding organ donation, each country needs to work on developing strategies to educate the community, lower the refusal of family members and overcoming logistical and operational problems to improve donation rates. Access to LT in the region is very heterogeneous. While some countries have no active LT programs, others as Brazil have the largest public transplantation system in the world. While some countries have only a few LT centers, others have too many LT centers performing an inadequate number of LTs. Further investigations focused on the strict analysis of specific variables including cultural, logistic and socio-economic factors inherent to each country individually would be interesting in the future to understand and improve LT access, transplant laws and allocation rules. Disparity to access to transplantation remain the major challenge in the region. Organ donation and LT should be performed by limited centers with the human and material resources needed to succeed along with the financial and government support on a legal framework that favors equality and justice for the patients. Cultural and educational efforts have to be accompanied with transparent public policies that will likely increase organ donation and activity in transplantation. 7
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