Living-Donor Liver Transplantation—The Need for Greater Transparency

Liver transplantation (LT) has evolved rapidly over the past two decades in South Asia (particularly in India) as an effective treatment for those with liver failure.^{1, 2, 3} Currently, India is performing over 3800 LTs in a year.⁴ The transplant programme is overseen by a regulatory authority, the National Organ and Tissue Transplantation Authority (NOTTO), and a self-reported registry has also been started.⁵ The outcomes of liver transplants are published regularly in peer-reviewed journals and are as good as anywhere else in the world.^6,7 Today, India is amongst the top 6 countries in the world for providing liver transplant services. It is no wonder that India attracts medical tourists who seek this treatment for a cost which is less than one-third of what they would pay in Western centres.^8,9 Although hepatologists, transplant surgeons, and the medical community in India are justifiably proud of these remarkable achievements; cautionary notes are sounded every now and then that point to the chinks in the armour of this great programme.^{10, 11, 12, 13} The primary aim of this paper is to review some of the challenges facing India's liver transplant programme and explore potential solutions for a course correction.

UNIQUE CHALLENGES POSED BY HEALTHCARE ENVIRONMENT

India's healthcare landscape presents several anomalous situations. Most of the tertiary care is provided in private institutions, with patients bearing the high out-of-pocket expenses.¹⁴ A large proportion of all liver transplants in India are performed as living-donor liver transplants (LDLTs) in private hospitals, with the public sector contributions remaining less than 20%.^11,15 Of the 3800 transplants done in 2022, more than 3000 (approximately 80%) were LDLTs and fewer than 800 were deceased-donor liver transplantations (DDLTs).⁴ Most of the liver transplant centres in India are a part of corporate hospitals and are led by a highly skilled senior surgeon, who has the additional onus of ensuring the transplant programme remains financially viable. Some transplant surgeons operate in several hospitals to try and maintain numbers and meet the clinical need.¹⁶ The consistent failure of the public sector to take up the challenge of LT was highlighted in an earlier editorial.¹¹

LACK OF TRANSPARENCY

Although a self-reported registry has been started,¹⁷ fewer than 50 out of a total of over 200 registered LT centres are entering data in the registry (Dr Sonal Asthana, in charge, Indian Liver Transplant Registry, personal communication 2024). About 20 LT centres (10%) are performing over 100 LTs per year, and most of the published outcomes are reported by these centres. It goes without saying that these reports may not be representative of several smaller centres that do not be participate in the registry. Furthermore, long-term follow-up data of foreign donors and recipients are often difficult to obtain.¹⁸ Doubts are still expressed in some quarters about the authenticity of claims made by ‘single-surgeon experiences’.¹⁹ Whilst some larger centres do publish adverse events, including donor deaths, there is evidence that not all donor deaths are reported.^{20, 21, 22, 23} It should be noted that India is not alone in this context. The enactment of the ‘Transplantation of Human Organs Act’ in 1994, with subsequent amendments in 2011 and 2014, has not led to the expected boost in deceased organ donation or DDLT. Hence, the need for living donation remains high. In India, as elsewhere, there are consistent stories of scams involving the live donation and subsequent sale of kidneys and other organs for transplantation.²⁴ One always fears similar dealings may be taking place in the field of liver transplantation to arrange ‘altruistic’ donors. India is not the only country where ethical and moral concerns are being expressed.²⁵

ETHICAL CONCERNS

LDLT is an accepted treatment for adults and has continued to gain traction despite ongoing ethical concerns.^{26, 27, 28, 29, 30, 31, 32, 33} Whilst ethical objections have waned over time, it must be understood that ethically, this procedure is very delicately balanced in a tripartite equipoise between donor safety, recipient outcomes, and the need for surgery.³⁴ It has been said that the continued privileges of the transplant community depend on the public's confidence.³⁵ Public trust in the system is crucial for organ donation, both for the deceased and the living.³⁶ An example of Europe must be remembered when public distrust resulted in a major fall in deceased donation.³⁷ Similar thoughts have been expressed elsewhere.^{38, 39, 40} Like Caesar's wife, whose actions must not only be good but also look good (‘must be above suspicion’), the actions of the transplant community must always appear reasonable, measured, and in the interests of their patient. When the life expectancy of the recipient after transplantation is expected to be short, some authors have advised LT programmes against pursuing LDLT because they consider the potential donor risks to outweigh the benefits.^41,42 A recent retrospective study suggested that LDLT for 19 patients with advanced hepatocellular carcinoma and macrovascular invasion had poor estimated post-transplant survival (nearly zero at 3 years).⁴³ The question here is whether the ethical considerations for donors before such transplants were justified. Aristotle cautioned in Book I, Chapter 3 of his Nicomachean Ethics, ‘we must not expect more precision than the subject matter admits’.⁴⁴

LACK OF AUDIT

A key challenge in India is the lack of publicly available robust audit. Like many other jurisdictions, we have no robust data on donor and recipient survival on all LDLT procedures. How can one decide if the LDLT in a given setting is justified? A recent meta-analysis of nearly 61000 living liver donors showed a major complication rate of 5.5% and a donor mortality of 0.06%.⁴⁵ Of note, psychological complications occurred in 7.6%, wound infections in 5.2%, and respiratory complications in 4.9%. However, earlier reports of much higher complication rates are also available. In one report, 40% of donors had complications, mostly Clavien grades 1 and 2: grade 1 (minor, n = 232); grade 2 (possibly life-threatening, n = 269); grade 3 (residual disability, n = 5), and grade 4 (leading to death, n = 3).⁴⁶ As expected, except for a few reports of early donor death in the lay press, we have no idea what the risk is to the donor in India. The majority of LT centres perform very few transplants, many even fewer than 10 (as mentioned earlier, most of the published data comes from 20 odd major centres).^47,48 What kind of learning curve should we expect or the public accept?

SANCTITY OF INFORMED CONSENT

Ethical risks in LDLT extend to coercion and organ trafficking, exacerbated by the desperation of some recipients and their families.⁴⁹ Whilst Indian laws prohibit the sale of organs,⁵⁰ economic disparities and familial pressures create an environment where consent⁵¹ may not always be fully voluntary. Coercion is particularly prevalent amongst economically dependent donors, often women, who donate organs to male relatives. There are examples around the world of individuals selling their organ to provide food or shelter for their families, for example, following a natural catastrophe. Autonomy and financial independence might well have altered their decision.^52,53 Historical issues with organ trafficking in kidney transplants in India highlight the potential concerns for similar abuses in LDLT.

The intersection of altruism and exploitation underscores the need for independent assessments of the donor to ensure there is no coercion, the donor fully understands the risks and consequences and so gives fully informed consent, there are no medical or other contraindications, and the stated relationship is valid. This role is being done reasonably well by State Organ and Tissue Transplantation Organisation (SOTTO) representatives. However, to retain public confidence and ensure good governance, there needs to be full transparent in terms of donor safety and recipient outcomes.⁵⁴ Unfortunately, there is a temptation to ignore negative events about the donor's health.⁵⁵ There is probably no such thing as a free and informed donor in living liver donations between parents and their children as most parents would take enormous risk to save the life of their child.⁵⁶ For example, patients are likely to agree to interventions when they are told, there is a 95% chance of recipient survival and a 5% chance of donor death.⁵⁷ However, even if it is clear what risks the donor is willing to accept, it is mandatory to determine what risks for the donor are to be considered acceptable by the surgeon and the public. With increasing experience, contraindications to living donation are becoming fewer, so assessment of the medically complex donor is more challenging.⁵⁸ Medical issues are not the only factors that need consideration. For example, postdonation pregnancies are at a greater risk of adverse maternal outcomes than predonation pregnancies (odds ratio: 5.21).⁵⁹ Another example is that should the donor develop liver tumours, resection is more problematic. Other reported long-term outcomes include hernias and bile leaks. The incidence will depend on many factors, such as lobe donated and year of transplant.⁶⁰

LDLT puts great pressure on the surgeon to follow the four recognised ethical principles of medicine: autonomy (the respect for the patient's right to self-determination), beneficence (the duty to do good), nonmaleficence (the duty to do no harm), and justice (the duty to treat all people equally and equitably). A donor's autonomy can be ensured in part at least by making certain the potential donor gives fully informed consent, but as discussed elsewhere, many potential donors are under often unstated emotional pressure to donate. As with all surgical interventions, it is not possible to be sure that no harm will come to the donor. It is also important to avoid actual or potential conflicts of interest if the same surgeon is assessing both donor and recipient; the physician is inherently at the risk of becoming an advocate of the sick patient's need for a graft at the expense of the welfare of the potential donor. A further potential conflict is that surgeons may be seen as having a financial interest in the decision to transplant. Of course, the surgeon (and other healthcare professionals) has the right to be reimbursed for their skill and expertise. These dilemmas can readily be resolved by the presence of an independent expert to ensure an accountable and transparent comprehensive donor evaluation.

“SHOOT AND SCOOT” TRANSPLANTS

A concerning trend in India involves transplant surgeons performing LDLTs across several hospitals, often in different cities, leaving postoperative care in the hands of local teams. Whilst the need for mentorship for senior surgeons cannot be denied, this practice should not evolve into a situation that mirrors short-term surgical camps for cataract or cleft lip surgeries, where outcomes are often suboptimal.^{61, 62, 63} Do such LDLTs by fly-in fly-out surgeons have the same rate of success as those where the surgeon himself is available to assess post-transplant issues? There are no data available on that. For example, a UK-based surgeon initiated a liver transplant programme in India by performing two paediatric LDLTs before departing.⁶⁴ Both children died shortly afterwards due to postoperative problems. Informal enquiry in 12 such centres has indicated one-year recipient survival may be less than 50% in such situations, but there is no prospective study conducted on this aspect. India's lack of centralised audits exacerbates the problem, leaving LDLT outcomes largely unverified. Regulatory authorities could, and we believe should, mandate both postdonation and post-transplant reporting to enhance accountability and patient safety.

PROBLEMS WITH ALF PROGNOSTICATION

LDLT for acute liver failure (ALF) is particularly challenging because of the limited timeframe both to assess the donor and give enough information so the potential donor can give fully informed consent. Several ethical concerns have been raised about it in the past.^{65, 66, 67,68} In addition, tools like the King's College Criteria (which many Indian centres use) developed to predict outcomes in the absence of transplantation were designed for Western populations and often fail to accurately predict outcomes in Indian settings.⁶⁹ This raises the apprehension of unnecessary transplants for patients who might have survived without surgery. However, the need to avoid unnecessary transplants must be balanced against the risk of patients dying without a transplant; prognostic models all have relatively wide confidence intervals, so application to an individual must be done with caution. ALF cases highlight the complexities of balancing ethical considerations with medical urgency, further emphasising the need for transparent audits and outcome reporting.¹⁶

WHAT CAN BE DONE?

Whilst making recommendations is easy, implementation of any change is always an uphill task. The transplant community (surgeons, physicians, anaesthetists, critical care specialists, and other members of the team) must rise to the challenge to make the programme more transparent. The grand initiative of voluntary registry can be a huge success if all stakeholders pledge to submit all the relevant data. If that seems far-fetched in the present state of affairs, the regulatory authorities will need to sharpen their focus on these issues. Steps that can make our LT programme truly great would be to ensure mandatory reporting and audits of outcome. NOTTO and SOTTO can mandate that outcomes and at least one-year follow-up data are submitted by all centres to create a centralised registry. This registry should be centrally funded, led by healthcare professionals, and overseen by independent lay members or regulators. The presence of an independent LT expert at the time of donor counselling can also be a confidence-boosting step. This is crucial for maintaining public trust and ensuring accountability. Efforts must be made to incentivise and strengthen public sector contributions to LT. The specialists must work cohesively as a team and contribute to providing an affordable LT programme for lower economic classes who are currently deprived of this wonderful treatment. Some other suggestions to boost DDLT in India have already been presented earlier.¹¹

LDLT represents a significant medical achievement, offering hope to patients with end-stage liver disease. We stress that the great majority of healthcare professionals involved in LDLT work with expertise, integrity, and to the highest professional standards. However, ethical concerns persist in some quarters, particularly in Asia, where donor safety and autonomy may at times be compromised, and postoperative care may be less than ideal in ‘fly-by-night’ surgeries. Unless the outcome data from all canters are transparently available, the sceptics will always question the true beneficence of all centres. Living donors place immense trust in transplant teams and assume personal risks for the benefit of recipients. This trust must be earned through rigorous ethical standards, transparent outcomes reporting, and robust regulatory oversight. Regulators must prioritise mandatory audits and feedback mechanisms to ensure ethical practices across India's LDLT programmes. We do believe that these registries should be centrally funded and led by the healthcare professionals involved in LDLT but with robust oversight from lay members and regulators. Until such measures are implemented, questions about the validity of LDLT practices in India will remain unresolved.

Finally, whilst we applaud the altruism and generosity of the living donors, it must be stressed that these people are putting their lives at risk for the sake of others. The main justification for living donation is the shortfall of organs from deceased donors. The success of living donation should not be allowed to divert attention and resources away from increasing deceased donation to meet the needs of those requiring a transplant and ensure the lives of healthy individuals are not put at risk.¹⁶

Credit authorship contribution statement

Anil Chandra Anand and James Neuberger were both involved in the manuscript preparation and have contributed equally. Both the authors have read and approved the manuscript.

Declaration of competing interest

The authors have nothing to report.

Funding

No funding was received for this study.

Disclosures

Neither of the authors has potential conflicts (financial, professional, or personal) which are relevant to this manuscript.