Overcoming barriers and expanding opportunities in liver transplantation in Mexico

Abstract

Liver transplantation (LT) is the only curative treatment for end-stage liver disease. Although Mexico has made important strides in surgical capacity and institutional development, the country continues to report one of the lowest LT rates in Latin America. Multiple challenges remain, including inequitable access to care, limited organ donation, and structural inefficiencies in allocation systems. To review the current status of LT in Mexico, describe historical trends, highlight significant barriers to progress, and discuss potential opportunities for program expansion. We conducted a narrative review incorporating data from the National Transplant Center (Centro Nacional de Trasplantes in Spanish), relevant peer-reviewed literature, and global benchmarks. The analysis focused on trends in liver transplant volume, donor types, etiology shifts, institutional disparities, and the impact of the coronavirus disease 2019 (COVID-19) pandemic. LT activity in Mexico increased from 25 transplants in 1999 to 297 in 2023. However, over 68% of transplants are concentrated in Mexico City, and only eight centers perform more than ten LTs per year. Deceased donors account for most grafts, while living donor transplants remain rare and mostly limited to private institutions. The national waiting list functions primarily as a registry rather than a priority-based allocation system. The COVID-19 pandemic further disrupted transplant programs, particularly in the public sector. Innovative approaches such as donation after circulatory death, hepatitis C virus-positive donor utilization, and advanced perfusion technologies are currently unavailable or underutilized in Mexico. Mexico's LT system faces geographic, regulatory, and resource-related limitations. To improve outcomes and ensure equitable access, strategic reforms focused on donor expansion, centralized allocation, perfusion technologies, and standardization of care are urgently needed.

Key Words: Liver transplantation; Organ donation; Mexico; Hepatitis C virus; Perfusion; Health systems; Health services accessibility

Core Tip: Liver transplantation in Mexico remains disproportionately concentrated in a few urban centers and significantly lags behind regional benchmarks. This mini-review highlights the historical development of the transplant system, ongoing challenges such as low donor rates and fragmented healthcare structures, and opportunities for innovation through donation after circulatory death protocols, hepatitis C virus-positive graft utilization, and machine perfusion strategies. Implementing national reforms could bridge the gap between transplant capacity and patient need.

INTRODUCTION

Cirrhosis, the end stage of chronic liver disease, represents a major public health concern, contributing to over one million deaths globally each year[1]. In Mexico, liver-related illnesses ranked as the fifth leading cause of death among the economically active population as of 2023[2]. Despite its profound impact on healthcare systems, cirrhosis remains under-recognized and underprioritized in health policies. Liver transplantation (LT) is currently the only effective curative therapy for patients with advanced liver disease.

National mortality data indicate a consistent upward trend in liver-related deaths, from 31528 cases in 2008 to 40052 in 2023, with a median of 36311 deaths per year (interquartile range: 32647–40184). Notably, 72.4% of the deceased were male, and 59.8% were between 25 and 64 years of age[2].

LT has significantly improved survival and quality of life in patients with end-stage liver disease. Globally, liver transplant activity increased by 6.5% from 2020 to 2021, reaching 34694 procedures performed[3]. The United States and the European Union lead in deceased donor liver donation (DDLD), with reported rates of 28.4 and 21.9 per million population (pmp), respectively. In Latin America, Uruguay reported the highest average DDLD rate during 2018–2022 (20.1 pmp), followed by Brazil (16.1 pmp), Argentina (15.1 pmp), and Chile (8.0 pmp)[3]. In contrast, Mexico, Peru, and Paraguay reported much lower average DDLD rates of 2.99 pmp, 1.36 pmp, and 1.2 pmp, respectively[3].

While Mexico has made progress in promoting organ donation and enhancing medical training related to LT, transplant activity remains limited concerning need, primarily due to inequitable access to healthcare and persistent organ shortages.

HISTORY OF LT IN MEXICO

LT was first attempted in Mexico in 1976, about a decade after Dr. Thomas Starzl performed the world's first successful liver transplant[4]. Motivated by early international successes, Dr. Héctor Orozco-Zepeda[4] conducted Mexico’s first LT on a 44-year-old woman with cirrhosis. Unfortunately, the patient did not survive the postoperative period. In response, Dr. Orozco-Zepeda and Dr. Héctor Diliz pursued advanced surgical training under Dr. Thomas Starzl in the United States. Upon their return to Mexico, they established an experimental dog transplant program at the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" in Mexico City, successfully mastering the technique within a year[4]. In March 1985, they performed the country’s first successful orthotopic liver transplant. By the end of 1990, 11 LTs had been completed at the same institution[5].

This early success positioned LT as a viable therapeutic option for end-stage liver disease in Mexico[3]. In 1999, the federal government established the National Transplant Center [Centro Nacional de Trasplantes in Spanish (CENATRA)] to oversee and regulate nationwide organ donation and transplantation activities[6]. Over the following decades, the annual number of LTs rose from 25 in 1999 to 297 in 2023, while the national transplant rate increased from 0.01 pmp to 2.3 pmp during the same period (Figure 1A and B). Despite this progress, LT activity in Mexico has plateaued since 2013, and current transplant rates remain among the lowest in Latin America[6].

Figure 1 Number of total liver transplants, liver transplants, and deceased donor livers in Mexico. A: Number of total liver transplants per year in Mexico (1999-2923); B: Number of liver transplants per million people in Mexico (1991-2923); C: Number of deceased donor livers in Mexico (2014-2023).

As of 2024, there are 84 CENATRA-accredited liver transplant centers across Mexico, with the majority located in Mexico City, Monterrey, and Guadalajara (Figure 2). Although this reflects ongoing efforts to expand transplant accessibility, the distribution is uneven. Most of these centers belong to the private sector, and only eight perform ten or more transplants per year, predominantly clustered in Mexico City. This geographic concentration limits access to transplantation for patients in other regions, raising concerns about the consistency and quality of care in low-volume centers.

Figure 2 Distribution of liver transplant centers by state in Mexico.

A critical limitation of the Mexican LT system is the lack of long-term post-transplant follow-up data. Only a few centers systematically report survival outcomes. Among these, 1-year, 3-year, and 5-year survival rates have been reported as 94%, 88%, and 88%, respectively[3,6].

ETIOLOGY SHIFTS OF CIRRHOSIS OVER THE RECENT DECADES

The introduction of direct-acting antivirals (DAAs) and the global rise in obesity have significantly altered the etiological landscape of cirrhosis, particularly in high-income countries such as those in Europe and the United States[7,8]. Hepatitis C virus (HCV), previously the leading global cause of cirrhosis, is now considered a curable infection, resulting in a steady decline in HCV-related cirrhosis cases. In contrast, metabolic-associated steatotic liver disease (MASLD) has emerged as the predominant cause of cirrhosis in many Western populations[7-9].

This trend is also reflected in the Mexican experience. A historical study conducted at the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, one of the most active liver transplant centers in the country, reported that between 1976 and 2012, HCV was the leading cause of cirrhosis, followed by autoimmune liver disease and MASLD[3,10]. However, a more recent multicenter study involving five major transplant centers in Mexico City found that MASLD has become the leading etiology of cirrhosis, closely mirroring the shifts observed in Western nations. Alcoholic liver disease (ALD) and HCV were identified as the second and third most common causes, respectively[10].

These observational findings might suggest that the burden of MASLD will continue to rise in Mexico and globally[8,10]. This epidemiologic transition highlights the urgent need for tailored public health strategies to address the increasing prevalence of metabolic disorders (such as diabetes) and persistently high levels of alcohol consumption[11,12].

THE CURRENT STATE OF LT IN MEXICO

Mexico's healthcare system is divided into public and private sectors. The public sector comprises multiple institutions, including the Mexican Social Security Institute [Instituto Mexicano del Seguro Social in Spanish (IMSS)], which serves workers in the formal economy and their families; the Institute for Social Security and Services for State Workers (Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado in Spanish), which covers government employees; and the Institute of Health for Well-being (Instituto de Salud para el Bienestar in Spanish), which aims to provide care for individuals without social security, such as informal workers. Additionally, smaller systems serve specific populations, such as Mexican Petroleum Company (Petróleos Mexicanos in Spanish) and the armed forces (Fuerzas Armadas). The private sector includes a network of private hospitals and clinics that provide care for individuals with private insurance or the means to pay out of pocket. Although this dual framework was designed to provide broad coverage, disparities in access and quality of care between public and private sectors remain a major challenge[6].

Healthcare access, particularly LT, is highly variable across these subsystems. According to data from the CENATRA, 3246 LTs were performed in Mexico from 1991 through 2023, with most grafts originating from deceased donors. In 2023 Mexico recorded its highest annual number of LTs, reaching 297 transplants nationwide. These procedures were primarily concentrated in Mexico City (68.3%, n = 203), followed by Nuevo León (14.8%, n = 44), Jalisco (14.0%, n = 42), Sonora (1.6%, n = 5), Querétaro (0.9%, n = 2), and the State of Mexico (0.4%, n = 1), reflecting the geographic concentration of healthcare infrastructure and economic resources[6].

Concerning institutional participation, 44% (n = 132) of LTs were performed in Secretaría de Salud (SSA) hospitals, 36% (n = 107) in IMSS facilities, and 20% (n = 58) in private hospitals. The Hospital General de Mexico Dr. Eduardo Liceaga led with 60 transplants, followed by the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (n = 52), the Hospital de Especialidades Dr. Antonio Fraga Mouret at Centro Médico Nacional La Raza (IMSS) (n = 27), Hospital de Especialidades No. 25 (IMSS) (n = 26), and Centro Medico Nacional de Occidente (IMSS) (n = 16)[6].

Despite progress, Mexico continues to report one of the lowest organ donation rates pmp in Latin America and globally[3]. From 2014 to 2023, liver donations remained limited (Figure 1C). In 2023, only 300 Liver donors were registered, despite the identification of over 400 hospitals with the potential to serve as organ donation centers[3,6]. Most liver grafts came from deceased donors, with CENATRA recording 275 deceased and only 22 Living donors. Of the deceased donor grafts, 47% (n = 130) were allocated to SSA, 36% (n = 99) to IMSS, and 17% (n = 46) to private institutions. Geographically, most transplants occurred in Mexico City (n = 197), followed by Nuevo León (n = 41), Jalisco (n = 30), Sonora (n = 5), and Querétaro (n = 2)[6].

Living donor LT (LDLT) remains uncommon in Mexico, with only 22 cases reported in 2023. Notably, 55% of LDLTs were performed in private hospitals, demonstrating the disparities in access to complex surgical procedures across the public and private healthcare systems.

IMPACT OF CORONAVIRUS DISEASE 2019 PANDEMIC ON TRANSPLANTATION PROGRAMS IN MEXICO

Undoubtedly, the coronavirus disease 2019 (COVID-19) pandemic profoundly impacted LT outcomes and healthcare practices worldwide. A Brazilian study found that 38.9% of LT recipients infected with COVID-19 needed intensive care unit care, with a 64.3% mortality rate for those critically ill. In comparison, no fatalities were noted among patients with mild symptoms[13]. Furthermore, a systematic review showed that LT recipients faced similar risks of severe COVID-19 outcomes as non-transplant patients[14]. However, data from the United States revealed an increase in inpatient mortality and elevated rates of transplant rejection during the pandemic[15]. In addition, a European study indicated a 15% mortality rate among LT recipients who contracted severe acute respiratory syndrome coronavirus 2[16].

Importantly, vaccination was shown to reduce the severity of COVID-19 in liver transplant recipients, as demonstrated by a study conducted in Mexico[17]. The pandemic also led to a strategic modification in LT programs, prioritizing patients with hepatocellular carcinoma, while the number of transplants for ALD increased[18,19].

There was a substantial decline in LT activity in Mexico, particularly within public healthcare institutions. Globally, the reduction in transplantation procedures was more pronounced in public institutions (89%) compared to private ones (62%)[20]. This pattern extended to kidney, cornea, liver, and heart transplants, all of which experienced greater declines in the public sector.

Specifically, in Mexico, the number of liver transplants dropped dramatically from 224 in 2019 to only 72 in 2020, representing an 88% reduction in the public sector and a 35% reduction in the private sector[6]. This decrease was primarily attributable to the reallocation of transplant centers for COVID-19 care and a decline in organ donation during the pandemic[3,21].

CHALLENGES IN TRANSPLANT PROGRAMS IN MEXICO

Improving LT programs in Mexico requires more uniform access to healthcare to decrease disparities, and more specifically, commitment and accountability in the public sector. In addition, there is an urgent need to increase the donation rate so that donation after circulatory death (DCD) can be implemented[11,22-24], as well as investments in other technologies such as normothermic or hypothermic perfusion[25-28]. These innovations would not only increase transplant rates but could also help address geographic disparities[23].

IMPLEMENTATION OF DCD LIVER DONATION IN MEXICO

DCD is a promising avenue for expanding the liver donor pool in Mexico. The modified Maastricht classification[29] provides a framework for categorizing DCD scenarios from controlled (Maastricht III) to uncontrolled settings (Maastricht I and II). By implementing this classification, Mexico can more effectively identify and utilize potential DCD donors, particularly in controlled hospital environments, where logistics can be better managed.

A study analyzing Organ Procurement and Transplantation Network data from 1993 to 2007 revealed inferior outcomes for DCD liver transplants compared with donation after brain death. DCD livers exhibited lower one-year graft survival (79% vs 85%), higher rates of primary non-function (7%–10% vs 2%–3%), and more biliary complications. These findings highlight the increased susceptibility of DCD livers to ischemic injury, which can compromise the long-term graft viability[30].

A consensus by the International Liver Transplantation Society, published in 2021, identified several donor risk factors that negatively impact DCD outcomes. Factors such as prolonged warm ischemia time, older donor age, and high body mass index were associated with increased graft failure. For instance, warm ischemia times exceeding 30 minutes were associated with a 2.4-fold higher risk of graft failure. This emphasizes the critical need for meticulous management of the DCD process to mitigate these risks[31]. While DCD liver transplants in the United States saw a significant increase (147%) from 2009 to 2019, these only accounted for 14% of all liver transplants. An important obstacle is the lack of effective preservation mechanisms, leading to nearly 30% of DCD grafts being discarded[3]. This rate is likely even higher in Mexico.

UTILIZATION OF HCV-POSITIVE LIVERS

In Mexico, the utilization of HCV-positive liver donors remains limited, and little data suggests that a significant number of livers are discarded due to HCV positivity. Globally, however, the use of HCV-positive donor organs for transplantation, including liver transplants, has increased owing to the availability of highly effective DAAs. These drugs cure recipients’ post-transplantation, making HCV-positive donor organs an attractive way to improve the donor pool[25-27].

The main barriers to using HCV-positive donors are likely related to infrastructure and access to DAAs, as well as a lack of awareness of new therapeutic strategies[25]. Overcoming these challenges would involve investing in antiviral medications and establishing protocols designed to manage patients receiving HCV-positive grafts.

HCV-positive donors can be categorized as chronic or resolved infections [anti-HCV antibody (Ab)+ with or without nucleic acid amplification testing (NAT)+] or suspected acute HCV (Ab−/NAT+). A retrospective study by Myers et al[26], Analyzing United Network for Organ Sharing data from 2015–2019 demonstrated that HCV-positive livers in DCD transplants were non-inferior to HCV-negative livers in terms of patient and graft survival at 1 year and 3 years[28,29]. This suggests that HCV-positive status may not be a contraindication for DCD LT.

Initially, it was believed that patients with low model for end-stage liver disease (MELD) scores were ideal candidates for HCV-positive liver disease. However, a recent study (Bekki et al[27]), published in Transplantation, found that applying more stringent criteria for these patients resulted in significantly higher one-year graft survival rates (97.1% vs 91.8%) compared to recipients of HCV-negative livers[27]. This suggests that the general selection criteria for DCD HCV-negative donors can be utilized for HCV-positive livers.

PERFUSION TECHNOLOGIES FOR DCD LT

Perfusion technologies, such as hypothermic oxygenated perfusion (HOPE), normothermic regional perfusion (NRP), and normothermic machine perfusion (NMP), are cornerstones in the preservation of livers obtained from donations after DCD[32,33]. These techniques mitigate ischemia–reperfusion injury, which is a common challenge in DCD liver transplants[22]. These techniques are briefly discussed in the following paragraphs: (1) NRP: This procedure restores circulation to the donor’s abdominal organs using extracorporeal membrane oxygenation before organ retrieval. By maintaining organs at body temperature, NRP extends preservation time and improves organ quality, reducing biliary complications in DCD LT[34]; (2) HOPE: The liver is perfused with oxygenated solutions at low temperatures before transplantation. HOPE minimizes ischemic injury and helps prevent ischemic cholangiopathy, a frequent complication of DCD transplants[35,36]; and (3) NMP: It preserves livers at body temperature by continuously perfusing them with oxygenated blood. NMP provides real-time assessment of liver function and shows potential in reducing primary graft dysfunction, although its impact on ischemic cholangiopathy is still under review[36].

These strategies present significant advantages for DCD liver transplants by addressing ischemia–reperfusion injury and expanding the donor pool, especially in resource-limited settings such as Mexico[22,35]. However, implementing these strategies requires substantial technology, training, and infrastructure investment.

To our knowledge, no DCD liver transplants have been performed in Mexico. The primary barriers include limited awareness among healthcare providers, lack of advanced perfusion technologies, and an absence of regulatory frameworks supporting DCD[22]. Additional challenges include cultural attitudes towards end-of-life care, inadequate medical infrastructure, and legal constraints that complicate the implementation of DCD programs. Coordinated efforts are needed to improve public and professional awareness, provide specialized training, and invest in preservation technologies such as HOPE, NRP, and NMP to enable DCD LT in Mexico. Furthermore, regulatory updates that support DCD protocols and initiatives to promote public acceptance could help expand the donor pool and improve transplant outcomes nationwide[31,34].

DECENTRALIZATION OF LT IN MEXICO

Decentralizing LT services in Mexico is essential to improve access and equity. Currently, most LT procedures are concentrated in major cities such as Mexico City, Monterrey, and Guadalajara, leading to pronounced geographic disparities that limit transplant access for patients in underserved regions. Establishing transplant centers in other parts of the country could reduce this inequity by redistributing medical resources and alleviating the burden on high-volume centers[3].

PUBLIC HEALTH CHALLENGES IN MEXICO

Mexico’s current organ allocation system presents multiple structural challenges. The General Health Law allows donor-generating hospitals substantial autonomy in selecting recipients, resulting in a decentralized allocation process. Unlike centralized systems in other countries, where allocation follows a unified national waiting list and is based on transparent criteria (e.g., MELD score), Mexico lacks such standardization, which hampers fairness and accountability in organ distribution.

The absence of a centralized and prioritized national waiting list makes equitable organ allocation difficult. Furthermore, transplant centers are not mandated to disclose detailed allocation data, limiting external compliance and performance evaluation. In practice, allocation is often driven by the donor center's interest rather than the recipient's urgency. This leads to scenarios where cold ischemia time is not the primary determinant in graft distribution.

Additionally, the logistics and financial burden associated with organ procurement are considerable. Despite Mexico’s moderate geographic extension, the fragmented healthcare infrastructure and lack of coordinated transportation networks make organ retrieval and distribution costly and inefficient. These burdens often fall on individual centers, particularly in the public sector, with limited financial and technical support.

The deployment of advanced perfusion technologies, such as NMP and HOPE, is an enhancement and a vital progression for graft preservation. Despite their demonstrated potential in significantly improving outcomes, the adoption of these technologies is hampered by prohibitive costs and the inadequate volume of available donations necessary to justify such investments. Additionally, the so-called “CENATRA waiting list” serves predominantly as a registry of eligible patients, rather than a dynamic, real-time priority list that reflects true medical urgency. This critical distinction emphasizes a profound limitation within the existing national transplant framework, underscoring the urgent need for reforms that will promote transparency, prioritize those in most need, and ultimately improve patient outcomes. It is essential that we advocate for these changes, not only to enhance the efficacy of transplant procedures but also to honor the lives waiting for this opportunity[3].

CONCLUSION

Improving regulatory oversight and standardization across LT centers in Mexico is essential to enhance programmatic quality and expand the scope of transplant indications. This includes the adoption of HCV-positive donors for HCV-negative recipients, supported by the widespread availability of DAAs, and the broader use of extended-criteria donors. The integration of liver perfusion technologies, such as hypothermic oxygenated and NMP, may further improve graft quality and post-transplant outcomes, benefiting patients, transplant programs, and healthcare providers.

These strategic advances are urgently needed to address the significant mismatch between the number of liver transplants performed and the actual demand, particularly given the growing number of certified transplant centers. Additionally, reducing pre-transplant mortality will require optimizing the process for patient inclusion on the transplant waiting list. The current registry system fails to reflect the national demand, underestimating the number of needy patients and impeding timely transplantation. Streamlining this process through a centralized, needs-based allocation model would represent a critical step toward equity and improved survival in the Mexican LT landscape.

ACKNOWLEDGMENTS

The authors gratefully acknowledge the Centro Nacional de Trasplantes’ invaluable contributions to ensuring public access to national transplant data, which significantly informed and supported the development of this mini-review. We also thank the Secretaría de Salud for its ongoing commitment to improving healthcare delivery in Mexico, which provided the foundation for several of the analyses presented in this article.