Living donor liver transplantation: ethical considerations

Most solid-organ transplants performed in the Western world are from deceased donors. In the last decade, deceased donation rates have reached a plateau as the number of patients with end-stage organ disease has steadily increased, resulting in a large discrepancy between organ supply and demand. Living donor transplantation is one way to decrease this discrepancy. However, living donation is not universally accepted. For instance, living donation rates vary geographically (eg, living donation is more accepted in Asia than in the Western world) and depend on the organ donated (eg, kidney versus liver donation). In this article we will review the ethical principles guiding living donor liver transplantation, with emphasis on justification and safeguards that support the practice of adult-to-adult living donor liver transplantation, the most clinically and ethically challenging type of living organ donation. Our ethical justification will include a presentation of triangular or tripartite equipoise, a framework that aims to balance donor safety, expected recipient outcomes, and need.     

U.S. system for organ procurement and transplantation.

The establishment and responsibilities of the organ procurement and transplantation network in the United States are discussed, and the process of receiving an organ transplant through the system is described. The National Organ Transplant Act of 1984 provided for a federally funded network for organ procurement and transplantation, which would function as a private, non-profit organization. This organization is the United Network for Organ Sharing (UNOS). UNOS monitors the activities of and provides service to transplant centers and organ procurement organizations (OPOs). The names of all candidates awaiting cadaveric organ transplants are placed on a central waiting list maintained by UNOS; UNOS also is responsible for maintaining a scientific registry to collect relevant data from transplant centers on the recipients of organ transplants. Although there is a national list of more than 25,000 persons waiting at any given time for a cadaveric organ, there are far fewer actual organ donors (less than 5000 in 1991). The hospital's best resource with respect to the donation process is the local OPO, which provides services related to organ donor referral, evaluation, and surgical recovery. The organ donation process consists of eight components: donor identification, referral, evaluation, consent, management, recovery of organs, allocation, and follow-up. An organ recovery coordinator from the local OPO helps the hospital staff in determining donation potential, seeking consent from the next of kin, and managing the donor after consent has been obtained. The OPO--never the donor's family or their insurer--is billed for charges relating to the donation. The OPO then bills the costs associated with the donation to the transplant centers receiving each organ for implantation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Live-donor nephrectomy

Six decades after its first implementation, kidney transplantation remains the optimal therapy for end-stage renal disease requiring dialysis. Despite the incontrovertible mortality reduction and cost-effectiveness of kidney transplantation, the greatest remaining barrier to treatment of end-stage renal disease is organ availability. Although the waiting list of patients who stand to benefit from kidney transplantation grows at a rate proportional to the overall population and proliferation of diabetes and hypertension, the pool of deceased-donor organs available for transplantation experiences minimal to no growth. Because the kidney is uniquely suited as a paired organ, the transplant community's answer to this shortage is living donation of a healthy volunteer's kidney to a recipient with end-stage renal disease. This review details the history and evolution of living-donor kidney transplantation in the United States as well as advances the next decade promises. Laparoscopic donor nephrectomy has overcome many of the obstacles to living donation in terms of donor morbidity and volunteerism. Known donor risks in terms of surgical and medical morbidity are reviewed, as well as the ongoing efforts to delineate and mitigate donor risk in the context of accumulating recipient morbidity while on the waiting list.     

Increasing Consumer Awareness of the Need for Organ Donation

Abstract

Organ transplantation can save lives. Significant advances and successes in transplant technology have resulted in an increase in the survival of organ transplant recipients. However, the needed demand for the supply of organs for transplantation continues to exceed the available supply. This article addresses some of the challenges of organ procurement and offers possible strategies to improve consumer awareness of the need for organ donation.     

供体特异性调节性T细胞在肝移植免疫耐受中的意义

免疫耐受是器官移植的终极目标。尽管目前对于移植术后免疫耐受的探索很多,但大多处于试验阶段,应用于临床的方案甚少。对调节性 T细胞诱导免疫耐受的研究较为透彻,但供体特异性调节性 T细胞因其比例较低、制备困难,在移植免疫中的研究相对较少。本文从调节性 T细胞的共性、供体特异性调节性 T细胞的抑制功能、体外培养技术、胸腺移植等方面出发,总结供体特异性调节性 T 细胞在近年的研究热点,以期为临床研究提供新思路。     

Trends in kidney transplantation over the past decade

Kidney transplantation offers patients with end-stage renal disease the greatest potential for increased longevity and enhanced quality of life; however, the demand for kidneys far exceeds the available supply. This has led to an increase in the number of people on waiting lists and an increase in waiting time. In the US, the overall median wait time was 2.85 years in 2004. The projected median waiting time for adult patients awaiting a deceased donor kidney in 2006 is 4.58 years. The renal transplant community has pursued multiple avenues in an attempt to increase the donor pool, but this remains a major challenge. In the last decade, the number of live donor kidney transplants performed in the US and Canada has doubled and represents just over 40% of all donor kidneys. Among deceased donor kidneys, the largest percentage increases were seen in expanded criteria donor and donation after cardiac death kidneys. In the last decade, the age distribution among donors, and among patients on waiting lists or receiving a renal transplant, has shifted towards older age groups. There have been dramatic shifts in baseline immunosuppression with increased usage of induction agents and the nearly universal replacement of azathioprine by mycophenolate. Additionally, tacrolimus use has increased from 13% to 79% at discharge, while ciclosporin (cyclosporine) use has fallen from 76% to 15%. Although 1-year graft survival rates are excellent, only modest improvements have been observed in long-term graft survival rates in the last decade. Thus, efforts have shifted from improving early graft outcomes to altering the natural course of late graft failure. Death of transplant recipients from cardiovascular disease, infection and cancer remains an important limitation in kidney transplantation. Continued success in kidney transplantation will require increased numbers of donors, both living and deceased, as well as reduction in the primary causes of late transplant loss, namely premature patient death with a functioning graft and chronic allograft nephropathy.     

Pesticide-Poisoned Patients: Can They Be Used as Potential Organ Donors?

Introduction

The gap between the number of patients on transplant waiting lists and patients receiving transplants is growing. Use of organs from donors who have died following pesticide exposure remains controversial. This study reviews the literature related to transplantation from this group.

Methods

A literature search was undertaken on PubMed using the following keywords: ‘insecticide’, ‘pesticide’, ‘rodenticide’, ‘organophosphate’, ‘carbamate’, ‘paraquat’, ‘poisoning’, ‘toxicity’, ‘overdose’, ‘intoxication’, ‘ingestion’, ‘organ donation or procurement’, ‘transplant’, ‘allograft transplant’, and ‘expanded criteria organ donation’; 21 specific pesticides/insecticides were also added to the search; the indexes for EAPCCT/NACCT meeting abstracts 2008–2017 were also searched. Identified publications were reviewed and if described human donation/transplantation of ≥?1 solid organ(s), the following was extracted: (i) compound(s) ingested; (ii) donor demographics; (iii) organ(s) transplanted; and (iv) graft function at follow-up.

Results

Ten papers were identified describing 20 fatalities (1999–2017) related to the following pesticide exposures: organophosphate, 8 cases; aldicarb, 4; paraquat, 3; parathion, 1; malathion, 1; carbofuran/carbamate, 1; carbamate, 1; and brodifacoum, 1 and no further cases were identified from EAPCCT/NACCT abstracts. Donors were aged 12–50 (25.9?±?11.9) years. Forty-four organs were transplanted: 28 kidneys, 7 livers, 6 corneas, and 3 hearts. Forty recipients had outcome reported: 3 (7.5%) patients died, 3 (7.5%) had graft failure/dysfunction and 34 (85.0%) had good graft function. Overall survival with good function was 96%, 71%, 83%, and 67% for kidneys, livers, corneas and hearts respectively.

Conclusion

Review of the published literature suggests that solid organ donation following exposure to a pesticide is associated with good short-to-medium-term graft organ function following transplantation, particularly for transplanted kidneys and corneas.

     

Candidate selection criteria for living donor liver transplantation

Living donor liver transplantation is a new surgical technique that challenges the assumptions of the current system for allocation of livers for transplantation. Arguments based on justice in the setting of scarcity, and the consequent need for triage, do not apply. The risk to the living donor, an order of magnitude higher than that for kidney donation, raises different ethical concerns related to autonomy, what constitutes an acceptable risk-benefit equation, and who is to decide.     

Donation after cardiac death in abdominal organ transplantation

This article reviews the field of donation after cardiac death, focusing on the history, ethicolegal issues, clinical outcomes, best practices, operative techniques, and emerging strategies to optimize utilization of this resource. Donation after cardiac death is one effective way to decrease the organ shortage and has contributed the largest recent increase in abdominal organ allografts. Currently, donation after cardiac death organs confer an increased risk of ischemic cholangiopathy after liver transplant and of delayed graft function after kidney transplant. As this field matures, risk factors for donation after cardiac death organ transplant will be further identified and clinical outcomes will improve as a result of protocol standardization and ongoing research.     

Using Drug-Intoxicated Deaths as Potential Organ Donors: Impression of Attendees at the American College of Medical Toxicology 2014 Annual Scientific Meeting

Introduction

Over the last decade, there has been a reduction of organ donation from intracranial haemorrhage-, stroke- and blunt trauma-related deaths in the USA. There has been a corresponding increase in the use of drug-intoxicated patients as organ donors from 2.1 % in 2003 to 6.8 % in 2013.

Methods

Questionnaire survey of attendees at the American College of Medical Toxicology 2014 Annual Scientific Meeting breakout session on transplantation from deaths related to poisoning was performed. Participants were asked whether they would recommend the use of solid organs from cocaine- or carbon monoxide-related death before and after the breakout session.

Results

Forty-eight US participants (attending 23, fellow 15, resident 3 and other (including non-medical) 7) completed the survey, and 97.8 and 89.1 % of participants would consider cocaine- and carbon monoxide-related deaths for potential organ donation pre-breakout session, respectively; this increased to 100 % for both post-breakout sessions. There was variability in the consideration of different solid organs (the heart, lungs, liver, pancreas and kidneys)—76.2–95.2 and 76.2–85.7 % for individual solid organs for cocaine- and carbon monoxide-related deaths, respectively. For both scenarios, participants were least likely to consider potential heart donation (76.2 % of participants for both), which increased to 100 % following the breakout session.

Conclusions

Medical toxicologists have some reservation in recommending solid organs for transplantation from deaths from cocaine and carbon monoxide. Given the decrease in potential organ donors from typical methods of death, further work is needed to promote organ donation in deaths related to acute poisoning.     

Lung transplantation for cystic fibrosis.

Significant progress has been made since the first successful human heart-lung transplantation (HLT) for pulmonary vascular disease performed in 1981. The refinement of surgical techniques, use of cyclosporin as the main immunosuppressant, technique of distant organ procurement to expand the donor organ pool, and improved diagnosis and management of pulmonary infection and rejection have all contributed to this accomplishment. This has inevitably coincided with the extension of this procedure to other groups of patients with end stage heart and lung disease. Initially, HLT was offered to patients with cardiac disease associated with pulmonary hypertension. Because of the success, consideration was given to transplantation for parenchymal pulmonary diseases, initially pulmonary fibrosis and emphysema, and then suppurative lung disease such as in cystic fibrosis (CF). However, the application of HLT to patients with CF lagged behind because of concern related to the risk of sepsis, the systemic nature of the disease, malnourishment, and fear of recurrence of the epithelial CF defect in the transplanted lungs.     

Trust and trustworthiness in organ transplantation: good samaritan and emotionally related living donors

Organ transplantation, and living donor organ transplantation in particular, could not occur without society s trust in medicine and in transplant programs. This paper explains the importance of that trust and shows how the concept can be used to define the moral requirements for structuring organ transplant programs. The discussion goes on to outline what a trustworthy program must be, and to provide a conceptual perspective for drawing lines and setting boundaries for ethically acceptable living donor transplantation. It also explains the morally relevant considerations for accepting emotionally related or unrelated living donors.     

Xenotransplantation: application of disease resistance

1. Organ transplantation is now clinically routine for patients with end-stage organ failure. One major limitation in transplantation is chronic rejection involving the loss of the graft despite the use of immunosuppressive agents. Haematopoietic stem cell (HSC) chimerism, achieved through bone marrow transplantation (BMT), induces donor-specific tolerance to transplanted organs and prevents chronic rejection. 2. A second major limitation to organ transplantation is the donor shortage. Xenotransplantation, the transplantation of organs between different species, would have the ability to increase the availability of donor organs. 3. Current immunosuppressive therapies do not prevent the rejection of xenografts. Therefore, the only reliable method for achieving donor-specific tolerance to xenografts may require HSC chimerism. 4. In order to justify the use of BMT to induce transplantation tolerance in patients with non-life-threatening diseases, the morbidity and mortality associated with current conditioning regimens must be addressed. 5. The use of partial conditioning regimens to promote engraftment of xenogeneic HSC and the development of donor-specific tolerance may eventually make xenotransplantation in humans a clinical reality. 6. Additional advantages of xenotransplantation are the ability to genetically engineer the donor xenograft and resistance of some xenografts to infection by human viruses because of the species specificity of most viruses. 7. The clinical application of disease resistance for HIV and hepatitis B virus is the focus of the present review.     

Willingness to communicate about organ donation among migrant workers in mainland China:a cross-sectional questionnaire survey

Objective Voluntary organ donation is the sole legitimate source of deceased transplantable organs in China.Migrant workers have been major donors.The aim of this study was to examine willingness to communicate about organ donation and identify its predictors among Chinese migrant workers.Methods A total of 660 Chinese migrant workers were recruited into the study.Data were collected by the Chinese version of Organ Donation Attitude Scale,Death Attitude Profile-Revised (DAP-R),Self-Report Altruism Scale (SRA),Willingness to Communicate Sale (WTCS),and a socio-demographic data sheet.Results A total of 688 eligible migrant workers was approached and 660 workers completed the study with the response rate of 95.9％.Migrant workers reported moderate level of willingness to communicate about organ donation.The best-fit regression analysis revealed five variables that explained 32.6％ of the variance in willingness to communicate about organ donation.They were approval of organ donation,obstacle of organ donation,approach acceptance and death avoidance.Conclusion Migrant workers who had a stronger feeling about organ donation or death,and stronger altruism tendencies had a higher willingness to communicate about organ donation.Accordingly,the campaign strategy to promote family communication should enhance positive attitudes about donation,alleviate the fear of death and focus on the altruism element of donation behavior.     

Recent advances in solid organ transplantation

Advances in organ transplantation have come rapidly and consistently in recent years as the result of improved surgical techniques and immunosuppressive drug therapies. Experience gained in renal transplantation over the past 30 years has made this a standard therapeutic approach for treating chronic renal failure. This knowledge has been successfully applied to the transplantation of other organs to produce steadily increasing survival rates and improved quality of life. This article reviews the advances that have been made in solid organ transplantation and immunosuppressive drug therapy.     

Novel immunosuppressive agents in tolerance induction

Induction of transplantation tolerance remains a much sought-after but elusive goal with a potential promise of rendering patients free of long-term immunosuppressive drugs while maintaining good organ transplant function indefinitely. All currently studied strategies toward transplantation tolerance include using immunosuppressive agents for a limited time period to achieve tolerance. There are a growing number of agents that lend themselves to tolerance induction and these agents are considered herein. Such agents generally fall into the categories of lymphocyte depletion, costimulation blockade, and adjunctive agents such as rapamycin. Preliminary data using donor stem cells suggests that embryonic stem cells may have substantial advantages over conventional donor bone marrow for tolerance induction. These preliminary results are briefly reviewed as well. Tolerance has been achieved in a small number of organ transplant patients and such successes suggest that progress in the clinical arena is happening and is an obtainable result.     

<Emphasis Type="Italic">Caveat patiens</Emphasis> — ethical dilemmas in decision -making

More than 99,358 men, women and children are on organ transplant lists in the United States. Pressure on family members to donate organs can therefore be intense. The medical excuse was created to address this potential coercion. It is a fabricated anatomical or physiological reason given to a donor (with or without the donor’s request) that provides an immediate shield against coercive pressure by family and friends on the potential donor. While the long-term risks and benefits of the medical excuse have not been studied, they could arguably include: 1) Reinforced perception that donation is expected; hence, declining donation is aberrant, and requires legitimization by external authority; 2) Eroded family trust of transplant physicians; 3) Eroded family trust in the individual reporting a “true” medical excuse; 4) Falsification of potential donor’s medical record; 5) Development of “toxic secrets” in the family unit; 6) Paternalism; and 7) General erosion of trust in both health care providers and the healthcare system. This author proposes a system of transparent and balanced communication where both the potential donor and the transplant team are clearly cognizant of the voluntary nature of the purported donation and where provisions for “opting-out” occur at any point along the pre-transplantation continuum.     

Selling organs for transplantation

The need for transplant organs has far outstripped the supply of available cadaveric organs. Hundreds of people on waiting lists, who could be saved by transplantation, die each year. This severe shortage has justified the extension of transplantation to the use of living donors, but there are still not enough organs to meet the need. This paper discusses the justification for changing policies in order to encourage organ donation. It presents reasons for allowing payments to be made to families that donate cadaveric organs. It also presents reasons for allowing payments to be made to living donors, and guidelines for how an ideal policy could be structured.     

Progress in xenotransplantation

Organ transplantation is considered the most effective treatment for end-stage organ failure; currently it is limited by a severe worldwide shortage of human donor organs. This has led to investigation of the potential use of animals as organ donors. For a number of reasons, the pig represents the most likely organ donor candidate. Transplantation of a vascularised porcine organ into a human or non-human primate results in an immediate and dramatic rejection process, known as hyperacute rejection, which is mediated by the binding of pre-existing antibody to the porcine graft and the subsequent activation of host complement. Strategies aimed at preventing this initial rejection have been largely successful in experimental models. This has allowed attention to turn towards an understanding of the immunological barriers comprising the next phase of xenograft rejection, termed acute vascular rejection. This delayed rejection process appears to be a humoral event, and it is likely that the control of antibody synthesis will play a pivotal role in overcoming the current barrier to successful xenotransplantation.     

Public attitudes towards kidney transplantation.

A representative sample of 500 members of the public was interviewed about kidney transplantation. The survey showed that despite widespread awareness of the need for kidney donors only 4.4% of the respondents had completed a donor card. The small percentage holding kidney donor cards appears to reflect a failure to inform and motivate the general public. There was no evidence of any widespread objection to the procedures involved in obtaining cadaver kidneys, but there was strong objection to the introduction by law of an "opting out" system. The findings suggest how the numbers of potential donors could be increased without changing the law as regards consent to donation.