Ethical frontiers in liver transplantation

Abstract

Liver transplantation represents a pivotal intervention in the management of end-stage liver disease, offering a lifeline to countless patients. Despite significant strides in surgical techniques and organ procurement, ethical dilemmas and debates continue to underscore this life-saving procedure. Navigating the ethical terrain surrounding this complex procedure is hence paramount. Dissecting the nuances of ethical principles of justice, autonomy and beneficence that underpin transplant protocols worldwide, we explore the modern challenges that plaques the world of liver transplantation. We investigate the ethical dimensions of organ transplantation, focusing on allocation, emerging technologies, and decision-making processes. PubMed, Scopus, Web of Science, Embase and Central were searched from database inception to February 29, 2024 using the following keywords: “liver transplant”, “transplantation”, “liver donation”, “liver recipient”, “organ donation” and “ethics”. Information from relevant articles surrounding ethical discussions in the realm of liver transplantation, especially with regards to organ recipients and allocation, organ donation, transplant tourism, new age technologies and developments, were extracted. From the definition of death to the long term follow up of organ recipients, liver transplantation has many ethical quandaries. With new transplant techniques, societal acceptance and perceptions also play a pivotal role. Cultural, religious and regional factors including but not limited to beliefs, wealth and accessibility are extremely influential in public attitudes towards donation, xenotransplantation, stem cell research, and adopting artificial intelligence. Understanding and addressing these perspectives whilst upholding bioethical principles is essential to ensure just distribution and fair allocation of resources. Robust regulatory oversight for ethical sourcing of organs, ensuring good patient selection and transplant techniques, and high-quality long-term surveillance to mitigate risks is essential. Efforts to promote equitable access to transplantation as well as prioritizing patients with true needs are essential to address disparities. In conclusion, liver transplantation is often the beacon of hope for individuals suffering from end-stage liver disease and improves quality of life. The ethics related to transplantation are complex and multifaceted, considering not just the donor and the recipient, but also the society as a whole.

Key Words: Liver transplant; Organ donation; Ethics; Xenotransplantation; Transplant tourism; Gene editing

Core Tip: Liver transplantation stands as a beacon of hope for individuals battling end-stage liver disease, offering the promise of extended life and improved quality of life. However, behind the lifesaving potential of this procedure lies intricate ethical considerations that demand careful examination. In this article, we delve into the multifaceted ethical issues surrounding liver transplantation, exploring the allocation of scarce resources, the challenges of organ procurement and distribution, transplant tourism, and the implications of emerging technologies. As the use of artificial intelligence grows, we also explore its potential role in liver transplantation as well as the ethical issues that accompany it.

INTRODUCTION

Liver transplantation is a beacon of hope for end-stage liver disease (ESLD) patients. It offers a chance at extended life with restored health and returning to productive roles within their life stories. ESLD patients have manifold cardinal symptoms[1] and account for over 4% of global deaths[2]. Over decades, advances in surgical techniques, immunosuppressive therapies and organ procurement protocols have propelled liver transplantation from an initially experimental endeavor to its current high standard of care[3-5].

With the chasm between organ demand and supply, ethics remains at the center stage for organ procurement, allocation, and recipient selection[6,7]. Ethical principles such as justice, autonomy and beneficence guide shaping policies within transplant programs[8,9]. However, alongside the triumphs of transplantation, the concern of transplant tourism and organ trafficking underscores the importance of ethical governance[10]. More pertinently, proliferation of transformative technologies and regenerative medicine, innovations such as xenotransplantation[11] and gene editing[12], necessitate careful consideration of safety, efficacy, and societal impact. Lastly, with the emergence of artificial intelligence (AI) technology, ethical implications remain relevant.

In this narrative review, we discuss an overview of ethical issues relevant to liver transplantation and examine the complex interplay of medical innovation, moral philosophy, and societal values; and through a critical analysis of the available literature. A comprehensive and iterative literature search was done on PubMed, Scopus, Web of Science, EMBASE and Central from inception to February 29, 2024 using the following keywords: “liver transplant”, “transplantation”, “liver donation”, “liver recipient”, “organ donation” and “ethics”. Information from relevant articles surrounding ethical discussions in the realm of liver transplantation, especially with regards to organ recipients and allocation, organ donation, transplant tourism, new age technologies and developments, were extracted narratively by six independent authors (Table 1).

Table 1 Search strategy.

Items	Specification
Date of search	February 28, 2024
Databases searched	PubMed, Scopus, Web of Science, EMBASE and CENTRAL
Search terms used	“Liver transplant”, “transplantation”, “liver donation”, “liver recipient”, “organ donation” and “ethics”
Timeframe	Database inception to February 2024
Inclusion criteria	Studies that were in English that discussed ethical issues in the realm of liver transplantation. Studies that focused on organ donation, organ recipients and allocation, transplant tourism, and new age technologies
Selection process	The search and selection of articles were conducted by primary authors SVS, PYL and JYJL. These were reviewed and approved by senior authors HPNW, MYQL and VGS

SVS: Surya Varma Selvakumar; PYL: Pei Yi Loh; JYJL: Jovan Yi Jun Liau; HPNW: Hoi Pong Nicholas Wong; MYQL: Matthias Yi Quan Liau; VGS: Vishalkumar Girishchandra Shelat.

OVERVIEW OF NEW TECHNOLOGIES IN LIVER TRANSPLANTATION

The perpetual lack of liver donors impacts the wait time. Long wait times contribute to 28.9% mortality before receiving the transplant[13]. To mitigate this, advancements towards alternative sources of liver cells are investigated (Table 2). Some of these newer technologies include xenotransplantation from porcine sources, the development of liver organoids for cell therapy, and tissue engineering or liver organogenesis using stem cell therapy[14,15]. The usage of these alternatives to liver transplantation would potentially reduce the need for human liver donors.

Table 2 Recent developments for alternatives to traditional liver transplants.

Novel technologies	Description	Animal use	Stem cell use	Gene-editing
Xenotransplantation	Transplantation of animal livers into humans	Yes	No	Yes
Stem cell therapy	Usage of stem cells for the treatment of disease, involving the growth, differentiation, and implantation of these stem cells[15]. Includes organoid development, tissue engineering and whole liver bioengineering as relatively newer treatment options	No	Yes	Yes

XENOTRANSPLANTATION

Xenotransplantation refers to the transplantation of live cells, tissues or organs from non-human sources. Keith Reemtsma, an American transplant surgeon, performed a series of 13 chimpanzee-to-human kidney transplants in 1964[16]. Following these attempts, liver xenotransplantation was then conducted by Giles GR and his team, but without success[17]. After the development of tacrolimus, his team then performed two baboon-to-human liver transplantations, with one of the two patients surviving 70 days[18].

Although early attempts for xenotransplantation utilized primates such as chimpanzees and baboons due to genetic similarity and better compatibility with humans, the use of these primates were phased out as they were impractical due to limited availability and low breeding potential, as well as possessed risks of interspecies transmission of infectious diseases[19]. Current research thus delves into the usage of pig donors, as they can be raised easily and screened more thoroughly for microbes and infectious diseases[20,21]. Pigs also have high availability, good breeding potential and rapid growth compared to primates, thus serving as an ideal source for organ harvesting[22].

HUMAN INDUCED PLURIPOTENT STEM CELLS

Human induced pluripotent stem cells (hiPSCs) are artificial stem cells formed by reprogramming mature adult cells using a series of transcription factors to possess similar properties to embryonic stem cells[23]. These cells are capable of differentiating into all three germ cell layers, hence serving as a possible alternative source for liver cells[23,24]. In fact, these hiPSCs have been used to generate liver organoids[25], which are miniaturized organs mimicking the key structural, biological and functional properties of the key organ, and can be used for disease modelling[26]. With its potential scalable production, implantation of these liver organoids have been proposed as alternatives to traditional liver transplants, reducing the reliance on human liver donors[27].

Prior to the discovery of iPSCs, much of stem cell research was conducted using embryonic stem cells, which requires the harvesting and destruction of human embryos. As such, the usage of embryonic stem cells is ethically controversial[28,29]. With the development of iPSCs, embryonic material is no longer required.

To date, hiPSCs have been used to generate various tissues, organs and organoids. Organoids are miniaturized organs mimicking the key structural, biological and functional properties of the key organ, and can be used for disease modelling and developmental issues[26]. Currently, liver organoids have been used to serve as models for testing liver dysfunction during sepsis[30], or to perform preclinical drug testing for hepatotoxicity[31]. Implantation of liver organoids have been proposed as alternatives to traditional liver transplants, reducing the reliance on human liver donors. Recent developments in organoid development have also demonstrated a scalable production of tissue-like liver organoids, potentially opening avenues for liver organoid transplantation[27]. A recent study attempted the engraftment of cholangiocyte organoids in a human liver and showed success in the transplantation of extrahepatic organoids to repair human intrahepatic ducts[32].

ARTIFICIAL INTELLIGENCE

In addition to technologies that increase the availability of organs for donation, technologies for fair and optimal allocation of organs are relevant. The use of AI machine learning models have already been successfully applied in the prediction of graft steatosis post-transplant, via histopathological analysis of liver biopsy specimens[33]. AI is mooted to streamline the allocation process by allowing machine learning models to allocate livers based on ‘best benefit’ by predicting survival outcomes rather than the pre-existing ‘sickest first’ policies. Even in the process of allocation, AI has some storied use in the process of donor-recipient matching, with artificial neural network models being used to adequately match donors and recipients whilst successfully accounting for a predicted 3-month outcome post-transplantation. This may serve to reduce or eliminate the physician’s emotional burden of decision-making based on clinical judgment.

ETHICAL CONSIDERATIONS OF XENOTRANSPLANTATION

Humans are widely known to use nonhuman animals for various purposes, including as a source of food. The use has diverse purposes such as keeping pets, using as means of livelihood and transport, as well as direct consumption of animal body parts in diet. This testifies that, according to humans, the general value of nonhuman life is lower than the value of human life. This higher value assignment is at both counts: Intrinsic value as well as social worth. However, within the humans, moral pluralism prevails regarding the value of nonhuman life. For example, vegetarians consider nonhuman life as sacred and not apt to consume in diet, but permissible to use at pet or as a means of livelihood. Similarly, not all nonhuman life is accorded the same value. For example, followers of Islam do not consume pork or accept pharmaceutical products with porcine contents[34]. Thus, use of nonhuman resources for various human use is underpinned by religious, cultural, and other diverse viewpoints within the society.

Not all nonhumans have similar moral worth. For example, the ability to communicate and rational thinking is considered to confer intrinsic and innate worth to life. Thus, animals that lack such abilities are ascribed lower moral worth compared to animals that have such senses and abilities. Further, it is generally accepted that human race evolutionary descended from primates and hence use of primate as a source for organs has two paradoxical perspectives. Firstly, primates are likely to have biological similarity with humans and thus organ transplant is more likely to succeed due to this structural, functional, or molecular similarity. Secondly, primates are human ancestors, and thus humans must endeavor to use non primates rather than use as a means to selfishly achieve our own ends. Thus, the scientific pursuit of xenotransplant is intricately related to ethical values and societal perspectives.

The usage of xenotransplants includes risks for zoonotic infections. Michaels et al[35], for example, reported the detection of baboon cytomegalovirus transmission after a baboon-to-human liver xenotransplant. Other studies also demonstrate a significant reduction in xenotransplant survival following porcine cytomegalovirus (PCMV) infection. This requires that patients are adequately informed. Transparency is a key tenet in this process[36]. New diagnostic systems using polymerase chain reaction can detect and quantify PCMV in potential porcine donors to reduce transmission risk[37]. Other means to reduce risk of zoonotic infections is by deactivating endogenous retroviruses. One such study by Niu et al[38] utilized CRISPR-Cas9 inactivated porcine endogenous retrovirus (PERV) in a primary porcine line, and subsequently produced embryos through somatic cell nuclear transplant. They then implanted these genetically modified embryos into surrogate sows, hence producing PERV-inactivated pigs. Not all humans would have willingness to accept such organs, and neither is the human decision independent of the life situation. For example, many humans who refuse to accept such organs may change their views when they face the decision in face of terminal life-threatening organ failure when there is no other alternative. This phenomenon is not the same as double standards, but highlights the complexity of rational decision-making under pressure[39]. Many religious and spiritual leaders have already considered it permissible to accept generally non-acceptable therapies in face of life- threatening situations if a person wishes to receive[34]. Additionally, in a survey regarding blood transfusion in Jehovah’s Witness patients, Cahana et al[40] has reported that more than one third of healthcare providers responded that they would administer a blood transfusion despite the patient's refusal, one of the reasons being patients do not really understand ‘what it means to die’. Though blood transfusion is not same as liver transplant, this highlights the readiness of certain groups among diverse stakeholders to engage with morally complex issues.

Due to the novelty of xenotransplantation, ethical problems are raised by multiple stakeholders, particularly with regards to informed consent. We personally consider informed consent as a misnomer phrase as it ignores the basic idea if the patient or care recipient really understood the information provided. However, for the purpose of this essay, we will discuss informed consent as it is generally understood. Headway into the development of informed consent forms has been made, one example being the draft consent form created by USA’s Secretary’s Advisory Committee on Xenotransplantation[41,42]. Informed consent forms have also been proposed by the International Society for Stem Cell Research (ISSCR) and adopted in various countries such as Germany and Taiwan[43]. Being thoroughly informed throughout the consenting process is a key ethical consideration – further endeavours should delve into clarifying the consenting process and ensuring that organ recipients are told exactly what is being done to their body and enable them to understand reasonably foreseen issues. This is especially true in the unique context of xenotransplantation which has an obvious risk-benefit divergence – is this procedure likely to prolong and ensure good quality of life[44]? It is currently unclear if the risks of developing novel zoonotic infections far outweigh the potential benefits[45], and from an animal rights and welfare perspective, the humanity of such novel technologies is still not well established[46]. The recipient is mandated to participate in lifelong follow-up to detect potential transmission of infections to humans, a form of Ulysses contract. Withdrawal from the follow-up based on personal autonomy must be balanced against risk of infection transmission[47]. In the interest of public health, lifelong surveillance of the individual is required to assess and control a possible spread of zoonotic and infectious diseases[48]. Such doctrines may be difficult to enforce due to potential compromise to patient autonomy. The double standards in human behavior were clearly visible during the coronavirus disease 2019 pandemic, as many people expected others to follow quarantine rules while believing they deserved exemptions from those same rules[39]. As a result, enforcing these regulations created ethical challenges for healthcare providers, who had to spend extra time navigating legal discussions to find solutions.

ETHICAL CONSIDERATIONS OF HIPSC

The development of hiPSCs for liver organoid production brings about several benefits. Firstly, hiPSCs can be made from the patient’s own cell lines, bypassing the need for animal involvement in the process. This circumvents ethical concerns regarding animal rights for the breeding and harvesting of animal organs by not subjecting animals to any possible harm in the pursuit of transplant alternatives. From an ethical and utilitarian perspective, the cost-benefit analysis of such new technologies is an important consideration. In the US, for example, standard acquisition charges for a liver range from US$30250 to US$42100[49]. On the other hand, the estimated cost to bioengineer 35% of a liver using hiPSCs is $9.7M[50]. Due to the high costs and need for materials involved, this technology will thus be out-of-reach for the public. The large amount of funding required to further advance research into hiPSCs for liver transplantation also puts into question whether it is ethically justifiable to allocate vast amounts of economic resources into an unproven technology. As economic resources are finite, a policy must balance the investment cost with the number of potential beneficiaries.

The sourcing of allogenic hiPSC cell lines raises ethical concerns about the confidentiality and privacy of the donor’s information. As hiPSCs are sourced from donor cells, the genetic information of these cells can be sequenced to identify the donor and close relatives. Confidentiality is a professional duty of healthcare providers to refrain from disclosing the patient information unless for the benefit of patient or qualified exemptions. Privacy is a legal right of a person. Both are essential ingredients to ensure public trust is upheld. Despite attempts to ensure confidentiality of donors, increasing access and availability of genomic sequencing platforms and data potentially risks the identification of these donors, compromising their privacy[51]. Even so, delinking and anonymization of patient information may not be ideal, as future clinical applications and research may require the retrieval of donor information to match for compatibility[52]. As such, careful consideration must be taken when balancing between practicality and safeguarding of donor privacy from potential misuse.

The informed consent of donors is also another critical consideration for the cultivation of allogenic hiPSC cell lines for liver organoid growth. Due to the evolving nature of stem cell research, it is challenging to define the scope of usage of hiPSC cell lines, as potential research may open other opportunities in the future, which may be potentially objectionable from the viewpoint of the donor. As such, so as to prevent potential misuse of cell lines, donor consent should clearly indicate whether these cell lineages are restricted only to the current project and purpose, or whether they can be used for future projects beyond the time of tissue procurement such as transplantation[53]. The possible future commercial use and profit generation might also lead the donor to ask for a monetary reward in exchange of participation. If such information is withheld, then it can be legally challenged. For example, the family of Henrietta Lacks, the woman from whom HeLa cells were sourced in 1951, has sued for unethically profiting from the cell line[54].

ETHICAL CONSIDERATIONS OF AI

No domain of human sphere is devoid of technological influence and healthcare too is not immune to AI. AI can identify previously unseen insights, increase system efficiency and improve patient care and outcomes[55,56]. It is useful in health research and drug development, health systems management and planning, disease prevention and surveillance, and medical education. Sucher et al[57] posits that there is a certain degree of objectivity in allowing for AI to make allocation decisions on organ transplant given that machine learning, as a process, will utilize input from numerous databases to make an informed inductive decision. This can potentially minimize waiting time and costs in maintaining waiting lists, and, as Briceño et al[58] states, maintaining the clinical principles of ‘justice, efficiency, and equity’ by minimizing biased human input.

It is, however, important to understand the premise of AI-based decision making. Majority of AI learning models depend on inputs from pre-existing studies. This input-output system of learning instills the most glaring shortcoming of AI as the output data and subsequent decisions, is dependent on the quality of the input data with risk of ‘bias in bias out’. The herculean task of collating and determining the quality of vast datasets may ultimately rest on the shoulders of medical professionals and physicians[59]. There is, moreover, a growing concern about the inherent bias within AI algorithms. Perhaps most damningly, however, is that there may be a certain discomfort that arises when a potentially life-saving decision is contingent on the response from a machine-learning model, rather than the multidisciplinary healthcare teams, leading to patient dissatisfaction or disapproval. There is an unstated sense of security in having the team of clinicians directly in charge of the patient’s care making such decisions in tandem with the patient themselves, but this element of the ‘human touch’ may ultimately be negated, were AI to be used as the intermediary[60]. While humans or healthcare teams are required to explain or justify the decision-making and rational, the current AI systems do not have this capability and this epistemic opacity is called as black box medicine[61].

Perhaps AI can be used as an adjunct to supplement and augment human decision making. Ultimately, the onus is on clinicians to continue to refine AI models and their algorithms with the best patient outcomes in mind, and to use them prudently. As Mucenic et al[62] rightfully espouses, the concepts of ethics and justice ‘rest upon the human mind’, and the final decision lies in human hands. Public acceptance of the role of AI in healthcare seems to be tepidly positive, with emphasis placed upon accuracy, impartiality, and consistency[63]. Thus, it is entirely reasonable to expect AI integration within the allocative decision-making process.

GENERAL ETHICAL CONSIDERATIONS

Sociocultural influences: The sociocultural fabric has an integral role to play in shaping beliefs, and thus attitudes toward organ donation - this extends to include attitudes towards the use of nascent technologies in liver transplantation as well.

No religion formally forbids organ transplantation[64]. However, porcine xenotransplants have been viewed to be ideal choices over other donor sources such as non-human primates, due to the high productivity of porcine livers associated with high growth and reproductive rates as well as developments that could prolong their longevity in the human body[11]. This might be difficult to accept among religious communities that restrict the use of pigs in everyday consumption, such as the Muslim and Jewish people. Liver transplant patients in Turkey oppose xenotransplants especially from non-Halal animals, with 87.2% of participants considering their religious beliefs when making important decisions, and over half opposing organ or tissue transplantation from a non-halal animal to themselves or a relative[65,66]. That being said, xenotransplantation has also been welcomed on some accounts within the Muslim community, as it would then reduce the need for harvesting organs upon death and thus preserve the sanctity of the human body[64]. It is important to engage in continuous dialogue with religious leaders and the community, to ensure a balance between the prolongation of life that transplantation can offer as well as an alignment of the values and cultural practices among religious communities.

In addition, the societal viewpoint of these technologies greatly influences the ability to implement such methods. For example, in countries such as Japan and the Middle East, the strong cultural resistance to deceased organ donation leads to significantly lower organ donation rates[67]. A survey in Sweden found that 80% of the public and 90% of patients waiting for kidney transplants were in favour of continued research on xenotransplantation, highlighting a great acceptance for the technology[68]. However, a separate study conducted in Turkey demonstrated an opposition towards liver xenotransplantation, especially from non-Halal animals[65]. Such studies show that the acceptance of xenotransplantation varies based on regional, cultural, and religious reasons.

Regulations to liver transplant technologies: A regulatory framework must be set up for the usage of these new medical technologies. The usage of xenotransplantation would require an overseeing body to perform surveillance and diagnostic testing[69]. Similarly, the usage of stem cell therapy requires a third party overseeing the entire process of transplantation, from ethical sourcing of stem cells to the implantation. Currently, multiple guidelines related to the use of stem cells exists, with notable examples being the ISSCR guidelines[43] and the National Institutes of Health Guidelines for Human Stem Cell Research[70].

Ensuring fair allocation of liver transplant technologies: Many of the technologies we had discussed are still in their nascent phase, and oftentimes the modality for access to these technologies boil down to the selection of individuals for clinical trials that investigate their efficacy. Due to the novelty of these technologies, hidden risks and complications may arise during the process. As such, the first-in-human studies should ideally be conducted on patients with unfavorable outcomes if unable to receive a prompt organ transplant[71]. Subsequently, if these new technologies are eventually approved for usage, these developments may also reduce disparities in allocational justice as an additional benefit[72].

Potential graft recipients are subjected to a battery of clinical and biochemical assessments to ensure that they are suitable transplant candidates. This is done to ensure that the donor liver has the best chance of improving recipient survival. However, premorbid medical and lifestyle issues may warrant shifts in consideration in terms of liver transplant technology allocation.

Obesity, for example, may contribute to poorer short-term surgical outcomes and long-term risk of poor graft function[73]. This is compounded by the fact that ESLD patients do not have time to lose sufficient weight. However, ESLD and obesity are distributed rather inequitably across races and the socioeconomic rungs[74]. Alcoholism has also been an area of controversy if this should preclude access to the newest liver transplant technologies[75]. The utility of liver transplantation for individuals with alcoholic liver disease (ALD) has been stunted by its perceived futility, due primarily to 50% recidivism despite psychosocial interventions[72]. Contrary to this utilitarian viewpoint, however, deontological schools of thought hold that at least some acts (in this case, liver transplantation for ALD) are morally obligatory regardless of their consequences for human welfare[76]. There has also been the social preconception that people with ALD are responsible for their own plight, and hence are less deserving of priority to receive an organ transplant, however these fail to consider the driving forces behind alcoholism as a clinical entity[77]. Chiefly, socioeconomic and even genetic components drive chronic alcohol abuse, with those on the lower echelons of society being more susceptible. Marginalizing such individuals by denying them or de-prioritizing them for liver transplantation may thereby be punishing them, in a way, for exigent circumstances that are largely out of their control, and may even widen pre-existing socioeconomic gaps[78]. It is integral that society lyses all prejudices and preconceived notions in the treatment of all patients equally, to uphold the medical principles of beneficence, justice, and fairness[79].

TRANSPLANTATION ETHICS TRIANGLE

The ethical considerations for liver transplantation can be summarized by addressing the 3Ps of the transplant triangle: Patient, physician and policy (Figure 1). As advancements in medical technology such as AI continue to evolve, so too must our ethical frameworks adapt to address emerging challenges and complexities. By prioritizing ethical considerations alongside clinical expertise, we can strive to uphold the principles of justice, equity, and autonomy in the pursuit of life-saving transplantation for those in need.

Figure 1  Ethics triangle summarizing the ethical considerations of physician, policy and patient factors in liver transplantation.

FUTURE DIRECTIONS

Ethical considerations remain at the forefront of innovation, research and progress. A concerted effort is required to navigate the intricate interweaving of scientific advancement and ethical imperatives. Recognition of underlying ethical issues, awareness and education of ethical dilemmas are the key first step to resolve. Clinical ethicists and bioethicists should be involved in research protocols, scientific experimentation, and implementation procedures. One such avenue for future exploration lies in addressing ethical concerns surrounding interspecies organ transplantations. Research endeavours should prioritize the development of robust immunomodulatory strategies to minimize the risk of rejection and zoonotic transmission, ensuring the safety, efficacy and long-term utility of xenogeneic liver transplantation. Furthermore, the emergence of stem cell therapies offers unprecedented opportunities to overcome the limitations of traditional organ transplantation. Ethical issues such as informed consent, patient autonomy and equitable access to emerging treatment modalities should find a prominent place in public discourse. A deeper dive into the concerns related to genetic manipulation and long-term safety is due. Ethical frameworks have to be established to properly govern the creation and utilization of human-animal hybrids. Collaborative efforts between scientists, surgeons, policymakers and ethicists will be essential to navigate the complexities to ensure that management principles are still guided by the principles of beneficence, justice and respect for human dignity.

CONCLUSION

Liver transplantation is often the beacon of hope for individuals suffering from ESLD and improves quality of life. The ethics related to transplantation are complex and multifaceted, considering not just the donor and the recipient, but also the society as a whole. From the definition of death to the long term follow up of organ recipients, liver transplantation has many ethical quandaries. With new transplant techniques, societal acceptance and perceptions also play a pivotal role. Cultural, religious and regional factors including but not limited to beliefs, wealth and accessibility are extremely influential in public attitudes towards donation, xenotransplantation, stem cell research, and adopting AI. Understanding and addressing these perspectives whilst upholding bioethical principles is essential to ensure just distribution and fair allocation of resources. Robust regulatory oversight for ethical sourcing of organs, ensuring good patient selection and transplant techniques, and high-quality long-term surveillance to mitigate risks is essential. Efforts to promote equitable access to transplantation as well as prioritizing patients with true needs are essential to address disparities.