Clinical Best Practice Advice for Hepatology and Liver Transplant Providers During the COVID-19 Pandemic: AASLD Expert Panel Consensus Statement.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19), the illness caused by the SARS-CoV-2 virus, is rapidly spreading throughout the world. Hospitals and healthcare providers are preparing for the anticipated surge in critically ill patients, but few are wholly equipped to manage this new disease. The goals of this document are to provide data on what is currently known about COVID-19, and how it may impact hepatologists and liver transplant providers and their patients. Our aim is to provide a template for the development of clinical recommendations and policies to mitigate the impact of the COVID-19 pandemic on liver patients and healthcare providers. APPROACH AND RESULTS: This article discusses what is known about COVID-19 with a focus on its impact on hepatologists, liver transplant providers, patients with liver disease, and liver transplant recipients. We provide clinicians with guidance for how to minimize the impact of the COVID-19 pandemic on their patients' care. CONCLUSIONS: The situation is evolving rapidly, and these recommendations will need to evolve as well. As we learn more about how the COVID-19 pandemic impacts the care of patients with liver disease, we will update the online document available at https://www.aasld.org/about-aasld/covid-19-and-liver.

An international multicenter study of protocols for liver transplantation during a pandemic: A case for quadripartite equipoise.

BACKGROUND & AIMS: The outbreak of COVID-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. METHODS: We performed an international multicenter study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the quadripartite equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. RESULTS: Seventeen large- and medium-sized liver transplant centers from 12 countries across 4 continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a "sickest-first" approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors - recipient outcome, donor/graft safety, waiting list mortality and healthcare resources - for 7 countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. CONCLUSIONS: This four-dimensional model of quadripartite equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems. LAY SUMMARY: There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources during the COVID-19 pandemic. We describe a four-dimensional model of quadripartite equipoise that models these ethical tensions and can guide the regulation of transplant activity in response to the increasing burden on healthcare systems.

Transplantation for Alcoholic Hepatitis: Are We Achieving Justice and Utility?

Early liver transplantation for alcoholic hepatitis is a potentially life-saving treatment. As this practice becomes increasingly common, however, the liver transplant community is taking a fresh look at a familiar challenge: best stewardship of donor organs. Herein, we examine a few basic, necessary ethical and practical concerns relevant to this indication.

Ethical decision-making in simultaneous heart-liver transplantation.

PURPOSE OF REVIEW: Simultaneous heart-liver (SHL) transplants are only a small proportion of overall heart and liver transplantation, they have been increasing in frequency and thus challenge the equitable allocation of organs. RECENT FINDINGS: The incidence of SHL transplants is reviewed along with the outcomes of SHL transplants and their impact on the waitlist, particularly in the context of solitary heart and liver transplantation. The ethical implications, most importantly the principles of utility and equity, of SHL transplant are addressed. In the context of utility, the distinction of a transplant being life-saving versus life-enhancing is investigated. The risk of hepatic decompensation for those awaiting both solitary and combined organ transplantation is an important consideration for the principle of equity. Lastly, the lack of standardization of programmatic approaches to SHL transplant candidates, the national approach to allocation, and the criteria by which programs are evaluated are reviewed. SUMMARY: As with all multiorgan transplantation, SHL transplantation raises ethical issues of utility and equity. Given the unique patient population, good outcomes, lack of alternatives, and overall small numbers, we feel there is continued ethical justification for SHL, but a more standardized nationwide approach to the evaluation, listing, and allocation of organs is warranted.

Bi-organ paired exchange-Sentinel case of a liver-kidney swap.

Organ transplantation is the optimal treatment for patients with end stage liver disease and end stage renal disease. However, due to the imbalance in the demand and supply of deceased organs, most transplant centers worldwide have consciously pursued a strategy for living donation. Paired exchanges were introduced as a means to bypass various biologic incompatibilities (blood- and tissue-typing), while expanding the living donor pool. This shift in paradigm has introduced new ethical concerns that have hitherto been unaddressed, especially with nondirected, altruistic living donors. So far, transplant communities have focused efforts on separate liver- and kidney-paired exchanges, whereas the concept of a transorgan paired exchange has been theorized and could potentially facilitate a greater number of transplants. We describe the performance of the first successful liver-kidney swap.

Is there an ethical obligation to split every donor liver? Scarce resources, medical factors, and ethical reasoning.

SLT has the potential to counter the worldwide shortage of donor organs. Although the preferred recipients of SLT are usually pediatric patients, a more stringent ethical argument than the fundamental prioritization of children is to demonstrate that SLT of deceased donor organs could increase access to this potentially lifesaving resource for all patients, including children. Several empirical studies show that SLT also makes it possible to achieve similar outcomes to WLT in adults if several factors are observed. In general, it can be regarded as ethically permissible to insist on splitting a donor liver if, in an individual case, SLT is expected to have a similar outcome to that of WLT. The question is therefore no longer whether, but under what conditions SLT is able to achieve similar results to WLT. One of the main challenges of the current debate is the restricted comparability of the available data. We therefore have an ethical obligation to improve the available empirical data by implementing prospective clinical studies, SLT programs, and national registries. The introduction of 2 modes of allocation-one for patients willing to accept both SLT and WLT, and a second for patients only willing to accept WLT-would help to resolve the issue of patient autonomy in the case of mandatory splitting policy.

Needs must: living donor liver transplantation from an HIV-positive mother to her HIV-negative child in Johannesburg, South Africa.

The world's first living donor liver transplant from an HIV-positive mother to her HIV-negative child, performed by our team in Johannesburg, South Africa (SA) in 2017, was necessitated by disease profile and health system challenges. In our country, we have a major shortage of donor organs, which compels us to consider innovative solutions to save lives. Simultaneously, the transition of the HIV pandemic, from a death sentence to a chronic illness with excellent survival on treatment required us to rethink our policies regarding HIV infection and living donor liver transplantation . Although HIV infection in the donor is internationally considered an absolute contraindication for transplant to an HIV-negative recipient, there have been a very small number of unintentional transplants from HIV-positive deceased donors to HIV-negative recipients. These transplant recipients do well on antiretroviral medication and their graft survival is not compromised. We have had a number of HIV-positive parents in our setting express a desire to be living liver donors for their critically ill children. Declining these parents as living donors has become increasingly unjustifiable given the very small deceased donor pool in SA; and because many of these parents are virally suppressed and would otherwise fulfil our eligibility criteria as living donors. This paper discusses the evolution of HIV and transplantation in SA, highlights some of the primary ethical considerations for us when embarking on this case and considers the new ethical issues that have arisen since we undertook this transplant.

Evolving swaps in transplantation: global exchange, vouchers, liver, and trans-organ paired exchange.

PURPOSE OF REVIEW: With the ongoing organ shortage, several mechanisms to facilitate organ exchanges and expand the scope of living kidney or liver donation have been proposed. Although each addresses at least one barrier to transplantation, these innovative programs raise important ethical, logistical, and regulatory considerations. RECENT FINDINGS: This review addresses four recent proposals to expand living donor transplantation. For kidney transplantation, we discuss global paired exchange and advanced donation programs ('vouchers') and for liver transplantation, liver paired exchange. Lastly, this review considers trans-organ exchange. We explore the conceptual framework of the exchange, current status, benefits, and concerns for implementation among each of these evolving pathways. SUMMARY: Through highlighting novel mechanisms in organ exchange, greater awareness, discussion, or support can occur to create more avenues for transplantation. These innovative mechanisms require regulations and safeguards for donors to ensure informed consent, and proper follow-up is maintained.

Should living donor liver transplantation be an option when deceased donation is not?

When a liver transplantation candidate is declined for listing to receive a deceased organ, sometimes a loved one comes forward and offers to be a living donor. This raises the ethical question of whether a patient who is not eligible for deceased donor liver transplantation should be eligible for living donor liver transplantation. We compare living organ donation in kidney and liver transplantation and explore key ethical concepts of justice, fairness, and societal trust. Ultimately, because there is no alternative life-preserving therapy in end-stage liver disease, and because transplantation with a living donor organ does not involve removing a resource from the common pool of transplant organs, we argue that a standard of "slightly less benefit" than that required for deceased transplantation should be used to determine the acceptability of living donor liver transplantation.

Liver paired exchange: Can the liver emulate the kidney?

Kidney paired exchange (KPE) constitutes 12% of all living donor kidney transplantations (LDKTs) in the United States. The success of KPE programs has prompted many in the liver transplant community to consider the possibility of liver paired exchange (LPE). Though the idea seems promising, the application has been limited to a handful of centers in Asia. In this article, we consider the indications, logistical issues, and ethics for establishing a LPE program in the United States with reference to the principles and advances developed from experience with KPE. Liver Transplantation 24 677-686 2018 AASLD.

Transplanting organs from hepatitis B positive donors: Is it safe? Is it ethical?

Liver transplant centres throughout the USA face a huge shortage of liver organs for their wait-listed patients. Various types of innovations are being considered for expansion of this donor pool. Organs that were previously deemed to be high risk are now being considered for transplantation. For the last 25 years, hepatitis B core antibody (anti-HBc+) organs have been used for liver transplantation. While the initial transplantations did reveal a high incidence of de novo hepatitis (DNH) in the recipients, the medical knowledge and experience have evolved and this risk has been markedly decreased. In this paper, medical literature evaluating the safety of such organ transplants has been reviewed. There is strong evidence to suggest that using anti-HBc+ organs with appropriate prophylaxis after transplant is a safe practice with good patient and graft survivals. In the second half of the paper, we discuss whether it is ethical to use anti-HBc+ organs. We argue that the use of such organs is in compliance with the principles of medical ethics and that society at large benefits from the use of these organs. Hence, we recommend that the use of such organs is both safe and ethical and this practice should be continued in the future.

Transplantation for Alcohol-related Liver Disease: Is It Fair?

AIMS: Alcohol-related liver disease (ALD) is the second leading cause of liver transplantation performed in the USA and Europe. We aimed to provide a narrative review of the major ethical issues governing transplantation for ALD. METHODS: We performed a narrative review of the ethical concepts in organ allocation for ALD, including alcoholic hepatitis. RESULTS: Ethical concerns regarding organ allocation for ALD involve issues of urgency, utility and justice. Post-transplant outcomes for ALD patients are good and ethical considerations limiting organs solely because of alcohol etiology do not bear scrutiny. CONCLUSION: ALD will continue to be a major cause for liver failure. The main criteria for transplant in ALD should be the patient's risk of return to harmful drinking, alongside standard assessments of physical and psychosocial fitness for transplant.

Benefit in liver transplantation: a survey among medical staff, patients, medical students and non-medical university staff and students.

BACKGROUND: The allocation of any scarce health care resource, especially a lifesaving resource, can create profound ethical and legal challenges. Liver transplant allocation currently is based upon urgency, a sickest-first approach, and does not utilize capacity to benefit. While urgency can be described reasonably well with the MELD system, benefit encompasses multiple dimensions of patients' well-being. Currently, the balance between both principles is ill-defined. METHODS: This survey with 502 participants examines how urgency and benefit are weighted by different stakeholders (medical staff, patients on the liver transplant list or already transplanted, medical students and non-medical university staff and students). RESULTS: Liver transplant patients favored the sickest-first allocation, although all other groups tended to favor benefit. Criteria of a successful transplantation were a minimum survival of at least 1 year and recovery of functional status to being ambulatory and capable of all self-care (ECOG 2). An individual delisting decision was accepted when the 1-year survival probability would fall below 50%. Benefit was found to be a critical variable that may also trigger the willingness to donate organs. CONCLUSIONS: The strong interest of stakeholder for successful liver transplants is inadequately translated into current allocation rules.

Wickedness, Moral Responsibility, and Access to Transplantable Livers.

Under the current conditions of scarcity of transplantable livers, difficult decisions need to be made about access. There is a growing consensus that it is morally justified to give people with ARESLD lower priority than those whose need is not self-caused. The purpose of this article is to critically examine the conditions under which such prioritization is morally justified, by challenging arguments put forth by Walter Glannon and Daniel Brudney. There are serious theoretical and practical problems with these views, which have to do with the nature and scope of the (putative) moral duty not to contribute to the competition for scarce transplantable livers, and the difficulty in determining whether people are responsible for their weakness or even wickedness of character. These problems need to be resolved if we are to be morally justified in determining access based on causal and moral responsibility for being in need.

Swaps and Chains and Vouchers, Oh My!: Evaluating How Saving More Lives Impacts the Equitable Allocation of Live Donor Kidneys.

Live kidney donation involves a delicate balance between saving the most lives possible and maintaining a transplant system that is fair to the many thousands of patients on the transplant waiting list. Federal law and regulations require that kidney allocation be equitable, but the pressure to save patients subject to ever-lengthening waiting times for a transplant has been swinging the balance toward optimizing utility at the expense of justice. This article traces the progression of innovations created to make optimum use of a patient's own live donors. It starts with the simplest - direct donation by family members - and ends with voucher donations, a very recent and unique innovation because the donor can donate 20 or more years before the intended recipient is expected to need a kidney. In return for the donation, the intended recipient receives a voucher that can be redeemed for a live kidney when it is needed. Other innovations that are discussed include kidney exchanges and list paired donation, which are used to facilitate donor swaps when donor/recipient pairs have incompatible blood types. The discussion of each new innovation shows how the equity issues build on each other and how, with each new innovation, it becomes progressively harder to find an acceptable balance between utility and justice. The article culminates with an analysis of two recent allocation methods that have the potential to save many additional lives, but also affirmatively harm some patients on the deceased donor waiting list by increasing their waiting time for a life-saving kidney. The article concludes that saving additional lives does not justify harming patients on the waiting list unless that harm can be minimized. It also proposes solutions to minimize the harm so these new innovations can equitably perform their intended function of stimulating additional transplants and extending the lives of many transplant patients.

Geographic Disparities in Liver Availability: Accidents of Geography, or Consequences of Poor Social Policy?

Recently, a redistricting proposal intended to equalize Model for End-stage Liver Disease score at transplant recommended expanding liver sharing to mitigate geographic variation in liver transplantation. Yet, it is unclear whether variation in liver availability is arbitrary and a disparity requiring rectification or reflects differences in access to care. We evaluate the proposal's claim that organ supply is an "accident of geography" by examining the relationship between local organ supply and the uneven landscape of social determinants and policies that contribute to differential death rates across the United States. We show that higher mortality leading to greater availability of organs may in part result from disproportionate risks incurred at the local level. Disparities in public safety laws, health care infrastructure, and public funding may influence the risk of death and subsequent availability of deceased donors. These risk factors are disproportionately prevalent in regions with high organ supply. Policies calling for organ redistribution from high-supply to low-supply regions may exacerbate existing social and health inequalities by redistributing the single benefit (greater organ availability) of greater exposure to environmental and contextual risks (e.g. violent death, healthcare scarcity). Variation in liver availability may not be an "accident of geography" but rather a byproduct of disadvantage.

New concepts in acute-on-chronic liver failure: Implications for liver transplantation.

Acute-on-chronic liver failure (ACLF) is a recently defined syndrome that occurs frequently in patients with cirrhosis and is associated with a poor short-term prognosis. Currently, management of patients with ACLF is mainly supportive. Despite medical progress, this syndrome frequently leads to multiorgan failure, sepsis, and, ultimately, death. The results of attempts to use liver transplantation (LT) to manage this critical condition have been poorly reported but are promising. Currently, selection criteria of ACLF patients for LT, instructions for prioritization on the waiting list, and objective indicators for removal of ACLF patients from the waiting list in cases of clinical deterioration are poorly defined. Before potential changes can be implemented into decisional algorithms, their effects, either on the benefits to individual patients or on global transplant outcomes, should be carefully evaluated using objective longterm endpoints that take into account ethical considerations concerning LT. Liver Transplantation 23 234-243 2017 AASLD.

Global lessons in graft type and pediatric liver allocation: A path toward improving outcomes and eliminating wait-list mortality.

Current literature and policy in pediatric liver allocation and organ procurement are reviewed here in narrative fashion, highlighting historical context, ethical framework, technical/procurement considerations, and support for a logical way forward to an equitable pediatric liver allocation system that will improve pediatric wait-list and posttransplant outcomes without adversely affecting adults. Where available, varying examples of successful international pediatric liver allocation and split-liver policy will be compared to current US policy to highlight potential strategies that can be considered globally. Liver Transplantation 23:86-95 2017 AASLD.

Liver transplantation for patients with alcoholic hepatitis.

Alcoholic liver disease, considered as a self-inflected disease, is an example of how moral judgment may affect ethical exercise of medicine which requires equity and fair utilization of a scarce resource in a context of organ shortage. Some consider that selection process should prioritize access to liver transplantation (LT) for patients who develop liver failure "through no fault of their own" even if limiting care because of a patient's perceived responsibility has been considered unethical. The absence of improvement after alcohol withdrawal, the high short-term mortality risk and the poor predictability of the 6-month rule in post-LT relapse in alcohol consumption in AH patients not responding to medical therapy led to recommend an evaluation of LT. In the French-Belgian pilot study, 26 patients with severe AH not responding to medical therapy underwent early LT (eLT). Stringent selection criteria were applied. Six-month and 2-year survivals of eLT patients were better than that of non-transplanted matched controls: 77% vs 23% and 71% vs 23% respectively. Alcohol relapse occurred in 12% of patients after eLT. Three studies confirmed these results. The impact organ donation should be limited as showed by a recent survey and the efforts that should be made in public information campaigns based on scientific data and medical ethics. In conclusion, the ongoing accumulation of scientific evidence and requirement of ethical exercise of medicine lead to continue evaluating eLT as a therapeutic option in patients with severe AH not responding to medical therapy.

Liver transplantation for severe alcoholic hepatitis- The PRO view.

Although liver transplantation has become accepted as a life-saving treatment of last resort for most life-threatening liver disorders, the use of liver transplantation to rescue patients with severe alcoholic hepatitis unresponsive to medical therapy remains controversial. I propose the concepts that alcohol use disorder is an illness, that on occasion results in alcoholic liver disease and that treatment of alcoholic liver disease, including treatment of patients with severe alcoholic hepatitis, combines treatment of the alcohol use disorder and of alcoholic liver disease. From this I derive the following principal to govern selection of patients for liver transplantation of patients with alcohol use disorder: that alcohol use disorder should impact suitability for liver transplantation as a co-morbid disorder, in the same way as other common co-morbid disorders such as diabetes mellitus or systemic hypertension, are factored in the selection process. We should relate the risk of drinking relapse to the prognosis of the patient after transplantation, rather than in a binary construct of likelihood of maintaining abstinence vs drinking.