Liver Transplantation From Controlled Non–Heart-Beating Donors: An Increased Incidence of Biliary Complications.

Liver Transplantation From Controlled Non–Heart-Beating Donors: An Increased Incidence of Biliary Complications. Transplantation 2003; 75: 1659. P. Abt, M. Crawford, N. Desai, J. Markmann, K. Olthoff, A. Shaked CAN CONTROLLED NON–HEART-BEATING DONORS PROVIDE A SOLUTION TO THE ORGAN SHORTAGE? Liver transplantation is achieving excellent results in the modern era. However, disparity between demand of liver grafts and supply results in approximately 2,000 deaths on the waiting list every year in the United States, where there are more than 50,000 patients waiting for a kidney and an excess of 18,000 waiting for a liver transplant. Organs from marginal donors, live donors, split, and domino liver grafts have therefore been used to increase the organ supply for transplantation. Before brain death legislation, non–heart-beating donation (NHBD) was the only source of organs for transplantation. However, with the advent of brain-stem testing and superior results obtained with heart-beating donor organs, expertise in non–heart-beating retrieval was lost. But because of the shortage of organs for transplantation, interest in NHBD revived in the late 1980s. The reexamination of NHBD after an interval of nearly 2 decades has benefited from significant improvements in preservation methods, immunosuppression, and transplant surgical techniques. There are two main types of donations after cardiac death: controlled and uncontrolled NHBDs (1). Controlled donors are patients who suffered an irreversible brain injury but do not meet brain-death criteria and with whom a decision to withdraw treatment is made by the family and the attending physician. The decision to donate strictly follows and is independent from planned withdrawal of treatment. Uncontrolled donors are victims of unexpected cardiorespiratory arrest, which occurs either in the streets or in the hospital and in whom resuscitation attempts fail to restore cardiac function. Organs from these donors have a unique set of problems associated with increased duration of warm ischemia, which is usually longer and not accurately measurable. Methods of organ preservation need to be initiated before obtaining family consent. Delay in obtaining permission from the family for organ donation may compromise the viability of the organs. The main problem with NHBD is the inevitable period of warm ischemia, which may adversely affect tissue viability and graft function after transplantation. Although warm ischemic injury per se does not preclude successful transplantation, reduced tolerance to subsequent cold storage of organs from NHBDs has been shown when compared with grafts from heart-beating donors (2). Kidneys can withstand longer ischemia, and renal replacement therapy can provide a safety net in case of delayed graft function. This is not true of livers where primary nonfunction (PNF) invariably leads to emergency retransplantation or death. Early reports of liver transplantation from NHBD revealed a high incidence of PNF and hepatic artery thrombosis, with early graft survival of less than 50% (3). Short-term results with transplantation of livers and kidneys from uncontrolled NHBDs carry a significantly higher incidence of PNF or graft dysfunction. The shift in use of controlled NHBD and an increasing experience in donor selection led to a significant improvement in early outcome after liver transplantation, with PNF rates and graft survival comparable with that of heart-beating donation (4,5). Although the incidence of delayed graft function is significantly higher with kidneys from NHBDs than with kidneys from donors with a heartbeat, there is no difference in long-term outcome between the two types of graft (6,7). This is not yet known for NHBD livers. In this issue of Transplantation, Abt and colleagues suggest that livers from donors whose hearts have stopped beating may be more susceptible to biliary complications and to ischemic cholangiopathy in particular. There is experimental evidence that irreversible intrahepatic biliary lesions are related to the extent of warm ischemia (8), but their etiology is probably multifactorial. D’Alessandro and colleagues (4) reported a trend toward greater incidence of cholangiopathy in older donors, although the difference was not statistically significant. This caused a reduction in survival of the liver grafts from NHBDs compared with those from donors with a heartbeat. This may reflect a learning curve in the reexamination of NHBDs, and the recent reports of greatly reduced PNF rates of liver transplantation from NHBDs may well translate into improved long-term graft survival. In our recent experience of 16 liver transplants from NHBDs, at an average follow up of 8 months, only 1 of the 13 survivors developed an anastomotic biliary stricture. Ethical issues still constitute one of the main hurdles to the wider acceptance of NHBD. These include questions regarding the ambiguity and cultural perspective of death, issues about family consent, and premortem procedures or medications that subordinate the interest of the patient’s goal of organ preservation. Perhaps the greatest ethical question with NHBDs is measuring the period of suspension between life and death. A stand-off time is observed from the time of cardiac arrest to establish the demarcation between an individual’s status changing from that of a dying patient to that of a donor. Various protocols observe different times, including 2 minutes (Pittsburgh), 5 minutes (Institute of Medicine), and 10 minutes (Maastricht). This period is observed to eliminate the potential for spontaneous resuscitation. It is paramount that the conflict of interest in this area is minimized to make it an ethically acceptable procedure. If not meticulously addressed, such concerns could potentially damage the public trust toward transplantation and may produce a negative effect on all organ-donation rates. Broad guidelines should be standardized to increase the understanding and acceptance by the public, although strict national protocols could stop innovation. The renewed interest in NHBD has stimulated further research in ischemia-reperfusion and in new preservation techniques. There is good evidence that preservation times will be extended by the provision of continuous cellular substrate. Stimulation of in vivo conditions by ex vivo perfusion could also mean that marginal organs could be resuscitated for transplantation. Perfusion will also allow for assessing the viability of organs before transplantation. Extra corporeal graft-perfusion techniques would reduce the risk of PNF, allow extension of the graft preservation period, and expand NHBD to thoracic organs(9,10). Further expansion of the donor pool is urgently needed because alternative solutions, such as xenotransplantation, artificial organs, or stem-cell transplantation, are still experimental and are not going to be available for clinical use in the immediate future. Despite a higher level of delayed graft function, the results from non–heart-beating renal transplantation are good, with long-term function comparable with cadaveric organs. Short-term results with NHBD liver transplantation are improving, and more data are needed on their outcome. Techniques in the near future, such as machine-perfusion preservation, may further improve the results from non–heart-beating renal and extra renal programs. The potential increase in organ donation with a more wide-spread use of NHBD is limited and still difficult to estimate with precision but will provide some much needed help with the organ shortage.