Liver transplantation from controlled non-heart-beating donors

BACKGROUND: The use of organs from non-heart-beating donors (NHBDs) has been proposed as one way to increase the donor pool. However, few centers have transplanted livers from NHBDs. We report here the results of 19 liver transplants from controlled NHBDs. METHODS: From January 1993 through August 1999, 364 liver transplantations were performed from heart-beating donors (HBDs) and 19 liver transplantations were performed from NHBDs. Donor and recipient characteristics, posttransplant complications, and patient and allograft survival were compared. RESULTS: No differences in hepatic artery, portal vein, or biliary complications were noted between the groups. However, the rate of primary nonfunction was higher in recipients of livers from NHBDs (10.5% vs. 1.3%; P = .04). No difference in patient survival was seen between recipients of NHBDs or HBDs (72.6% vs. 84.8%; P =.36); however, allograft survival was lower in recipients who received livers from NHBDs (53.8% vs. 80.9%; P =.007). CONCLUSIONS: Liver transplantation from controlled NHBDs results in similar patient survival and post-transplant complications. However, primary nonfunction was higher and allograft survival was less in recipients of livers from NHBDs. The results of liver transplantation from controlled NHBDs are encouraging and should continue to be cautiously pursued as one way to help alleviate the current shortage of donor livers.     

The UK National Potential Donor Audit

As part of a series of measures designed to improve organ donation rates in the United Kingdom, a potential donor audit has been established by UK Transplant. The audit will identify the number of patients who could be solid organ donors and will establish the obstacles to donation. Results from the first full year of the audit indicate that the overall relative refusal rate for heart-beating solid organ donation is 41.5%. The age and gender of the potential heart-beating donor has little impact on the relative refusal rate, but relatives of ethnic minority groups are more than twice as likely to deny consent than those of white potential heart-beating donors.     

Transplantation of organs: natural limitations,possible solutions--a UK perspective

While the outcome following organ transplantation in the United Kingdom has never been better, the waiting list has never been longer and the organ shortage is now the most pressing issue. UK Transplant has invested in four initiatives to promote donor and transplant numbers: coordinating the coordinators, establishing donor liaison posts, improving living donor coordination, and encouraging non-heart-beating donation. The Potential Donor Audit to be introduced as soon as possible will clarify the likely maximum number of heart-beating donors. A major review of the legal framework covering donation and transplantation in England and Wales is currently underway. It is hoped that in due course the benefits of these initiatives will be translated into a rise in both donor and transplant numbers.     

Liver transplantation from maastricht category 2 non-heart-beating donors: a source to increase the donor pool?

INTRODUCTION: The demand for liver transplantation has increasingly exceeded the supply of cadaver donor organs. Non-heart-beating donors (NHBDs) may be an alternative to increase the cadaver donor pool. The outcome of 20 liver transplants from Maastricht category 2 NHBD was compared with that of 40 liver transplants from heart-beating donors (HBDs). After unsuccessful cardiopulmonary resuscitation (CPR), cardiopulmonary support with simultaneous application of chest and abdominal compression (CPS; n = 6) or cardiopulmonary bypass (CPB; n = 14) was used to maintain the donors. RESULTS: At a minimum follow-up of 2 years, actuarial patient and graft survival rates with livers from Maastricht category 2 NHBD were 80% and 55%, respectively. Transplantation of organs from these donors was associated with a significantly higher incidence of primary nonfunction, biliary complications, and more severe initial liver dysfunction compared with organs from HBDs. The graft survival rates was 83% for livers from NHBDs preserved with CPS and 42% in those maintained with CPB.     

Liver transplantation from Maastricht category 2 non-heart-beating donors

BACKGROUND: The demand for liver transplantation has increasingly exceeded the supply of cadaver donor organs. Non-heart-beating donors (NHBDs) may be an alternative to increase the cadaver donor pool. METHODS: The outcome of 20 liver transplants from Maastricht category 2 NHBDs is compared with 40 liver transplants from heart-beating donors (HBDs). After unsuccessful cardiopulmonary resuscitation (CPR), cardiopulmonary support (CPS) with simultaneous application of chest and abdominal compression (n=6), and cardiopulmonary bypass (CPB; n=14), which was hypothermic (n=7) or normothermic (n=7), were used to preserve the organs from NHBDs. Factors that may influence the outcome of livers from Maastricht category 2 NHBDs were also investigated. RESULTS: With a minimum follow-up of 2 years, actuarial patient and graft survivals with livers from Maastricht category 2 NHBDs were 80% and 55%, respectively. Transplantation of organs from these donors was associated with a significantly higher incidence of primary nonfunction, biliary complications, and more severe initial liver dysfunction compared with livers from HBDs. Graft survival was 83% in livers from NHBDs preserved with CPS and 42% in those maintained with CPB. No graft failed if the duration of warm ischemia did not exceed 130 min with CPR or CPS, and if the period of CPB did not surpass 150 min when this method was used after CPR, regardless if it was hypothermic or normothermic. CONCLUSION: Livers from Maastricht type 2 NHBDs may be used for transplantation if the period of warm ischemia during CPR or CPS does not exceed 130 min. Hypothermic or normothermic CPB after CPR preserves liver viability for an additional 150 min.     

Ischemic cholangiopathy after liver transplantation from controlled non-heart-beating donors-a single-center experience

BACKGROUND: Previous reports have shown that livers from controlled non-heart-beating-donors (NHBD) are associated with higher rates of primary failure and ischemic cholangiopathy of orthotopic liver transplantation (OLT) as a complication of the prolonged warm ischemia. METHODS: This retrospective review of activities from 1999 to 2006 examined donor characteristics of age, liver function tests, warm ischemic time before (1WITa) and after cardiac arrest (1WITb), cold ischemic time (CIT) and transplant results. RESULTS: Eleven NHBD retrieved livers were transplanted from "ideal" donors except for one elderly donor (73 years). Of the 11 recipients, 3 developed biliary cholangiopathy (27%). There were no episodes of primary graft nonfunction, but one recipient displayed primary graft dysfunction. Two recipients died: one due to biliary complications with sepsis (long CIT >10 hours, fatty liver), and the other due to aspiration pneumonia and hypoxic brain damage with normal liver function. One recipient required retransplantation owing to ischemic cholangiopathy (1WITb 45 min) at 6 months after OLT with a good result. The other eight recipients are alive (observation period 72 to 14 months) including six with normal liver function, one with biopsy-proven biliary ischemia and one with recurrent primary sclerosing cholangitis without biliary ischemic changes on biopsy. Among 164 heart-beating donors recipients transplanted in the same period, biliary complications occurred in 27 patients (16%), of whom 12 were leaks and 15 anastomotic strictures. CONCLUSION: NHBD were a good source for livers with reasonable early results. To avoid late complications especially ischemic cholangiopathy, caution is urged with the use of these organs as well as strict donor and ischemic time criteria.     

Self-organizing maps can determine outcome and match recipients and donors at orthotopic liver transplantation

BACKGROUND: There is a relative lack of donor organs for liver transplantation. Ideally, to maximize the utility of those livers that are offered, donor and recipient characteristics should be matched to ensure the best possible posttransplant survival of the recipient. METHODS: With prospectively collected data on 827 patients receiving a primary liver graft for chronic liver disease, we used a self-organizing map (SOM) (one form of a neural network) to predict outcome after transplantation using both donor and recipient factors. The SOM was then validated using a data set of 2622 patients undergoing transplantation in the United Kingdom at other centers. RESULTS: SOM analysis using 72 inputs and two survival intervals (3 and 12 months) yielded three neurons with either higher or lower probabilities of survival. The model was validated using the independent data set. With 20 patients on the waiting list and 10 sequential donor livers, it was possible to demonstrate that the model could be used to identify which potential recipients were likely to benefit most from each liver offered. CONCLUSIONS: With this approach to matching donor livers and recipients, it is possible to inform transplant clinicians about the optimum use of donor livers and thereby effectively make the best use of a scarce resource.     

Current practice regarding the use of fatty livers: A Trans-Atlantic survey

A strong association exists between the presence of steatosis in a donor liver for transplantation and the development of primary nonfunction in the recipient. Despite this, appraisal of the donor remains one of the least scientific aspects of the transplantation process, and many centers base their practice on subjective opinion, rather than objective data. We conducted this survey to illuminate controversial issues and highlight the variation of opinion and practice policies both between and within the United Kingdom and the United States. A simple, anonymous, one-page, 10-question survey with tick-box answers was sent to every practicing liver transplant surgeon in the United Kingdom. The same form was sent by E-mail to liver transplant surgeons in the United States with a current E-mail address listed in the American Society of Transplant Surgeons registry. In the United Kingdom, 16 of 19 surgeons polled responded (84.2%) and thus were considered representative. From the United States, there were 78 respondents from 52 centers, representing all 11 United Network for Organ Sharing regions. We found that current practice policies differ not only between nations, but also among centers in each country. US surgeons generally follow a more conservative approach, with greater emphasis on histological assessment. Dichotomous opinions exist on the significance of microvesicular steatosis in both countries. Most evident from this survey is that more research in the field is required to help answer these questions and allow for the safe use of all viable livers. (Liver Transpl 2002;8:545-549.)     

Successful organ transplantation from donors with Acinetobacter baumannii septic shock

Donor bacteremia with severe sepsis, especially due to gram-negative organisms, has been considered a contraindication to transplantation. Over a 6-month period we prospectively collected standardized data on all brain-dead, heart-beating organ donors with gram negative bacteremia and septic shock and the recipients of their organs in hospitals throughout Israel. Donors were treated with appropriate antibiotics for at least 48 hr prior to organ retrieval while recipients received 7 days of culture-specific antibiotics following transplantation. In total, 12 organs were transplanted (5 kidneys, 2 livers, 3 lungs and 2 hearts) from 3 donors with Acinetobacter baumannii bacteremia and septic shock. All patients were alive with good graft function 60 days following transplantation, apart from one of the heart recipients who died of primary nonfunction on the second postoperative day. Two recipients developed postoperative infections, none with Acinetobacter sp. (one Pseudomonas sp. urinary tract infection, one Klebsiella sp. central venous catheter sepsis).     

Factors affecting graft survival after liver transplantation from donation after cardiac death donors

BACKGROUND: Liver transplantation from donation after cardiac death (DCD) donors is an increasingly common approach for expansion of the donor organ supply. However, transplantation with DCD livers results in inferior graft survival. In this study, we examined donor and recipient characteristics that are associated with poor allograft outcomes and present a set of criteria that permit allograft survival that is comparable to that of donation after brain death (DBD) grafts in both low- and high-risk recipients. METHODS: The United Network for Organ Sharing/Organ Procurement and Transplantation Network Liver Transplantation Registry between January 1996 and March 2006 was investigated. Adult DCD liver transplants (n = 874) were included. RESULTS: A DCD risk index was developed using the statistically significant factors from a multivariate Cox model: history of previous transplantation, life support status at transplantation, donor age, donor warm ischemia time (DWIT), and cold ischemia time (CIT). Favorable DCD donor criteria were donor age < or =45 years, DWIT < or =15 min, and CIT < or =10 hr. Four risk groups were developed based upon index scores that showed different graft survival. Graft survival of the favorable DCD group (84.9% at 1 year, 75.2% at 3 years, and 69.4% at 5 years) was comparable to that for DBD liver transplantation irrespective of recipient condition. Increasing donor age was more highly predictive of poor outcomes in DCD compared to DBD, especially in recipients in poor preoperative condition. CONCLUSIONS: DCD livers from young donors with short DWIT and CIT should be given greater consideration in order to expand the number of available donor organs.     

The predictive value of donor liver biopsies for the development of primary nonfunction after orthotopic liver transplantation

Methods of accurately assessing the suitability of donor livers prior to transplantation are required if the incidence of primary nonfunction (PNF) is to be reduced. This study evaluated the ability of donor liver biopsies to predict the development of primary nonfunction after transplantation. From June 1987 until May 1990, 170 liver transplants were performed in 147 patients. A total of 124 donor liver biopsies were obtained and divided into three groups. Group 1 biopsies (n = 77) were obtained after revascularization of the liver, group 2 biopsies (n = 19) were obtained prior to donor hepatectomy but examined only after implantation, and group 3 biopsies (n = 28) were obtained as in group 2, but were examined prior to implantation. Three of 89 (3.4%) livers interpreted as having normal histology developed primary nonfunction, while one of 26 (3.8%) biopsies interpreted as having a minimal or moderate amount of fatty infiltration developed primary nonfunction. PNF occurred in 7 of 8 livers with severe fatty infiltration (3), hydropic degeneration (3), and centrilobular necrosis (1). A fourth liver with hydropic degeneration and poor function ultimately failed requiring retransplantation 8 weeks later. Analysis of liver function revealed progressive elevation in aspartate-aminotransferase, alanine-aminotransferase, lactate dehydrogenase, and serum ammonia (NH3) with increasing degrees of fatty infiltration. Donor age and weight was also found to be significantly higher in livers with fatty infiltration. This study suggests that donor liver biopsies demonstrating normal histology or minimal-to-moderate fatty infiltration function adequately, but that donor livers with severe fatty infiltration or hydropic degeneration function poorly and should not be transplanted.     

Liver transplantation from non-heart-beating donors: current status and future prospects.

Liver transplantation is the treatment of choice for many patients with acute and chronic liver failure, but its application is limited by a shortage of donor organs. Donor organ shortage is the principal cause of increasing waiting lists, and a number of patients die while awaiting transplantation. Non-heart-beating donor (NHBD) livers are a potential means of expanding the donor pool. This is not a new concept. Prior to the recognition of brainstem death, organs were retrieved from deceased donors only after cardiac arrest. Given the preservation techniques available at that time, this restricted the use of extrarenal organs for transplantation. In conclusion, after establishment of brain death criteria, deceased donor organs were almost exclusively from heart-beating donors (HBDs). To increase organ availability, there is now a resurgence of interest in NHBD liver transplantation. This review explores the basis for this and considers some of the published results.     

Donor diabetes mellitus is a risk factor for diminished outcome after liver transplantation: a nationwide retrospective cohort study

With the growing incidence of diabetes mellitus (DM), an increasing number of organ donors with DM can be expected. We sought to investigate the association between donor DM with early post-transplant outcomes. From a national cohort of adult liver transplant recipients (1996–2016), all recipients transplanted with a liver from a DM donor (n = 69) were matched 1:2 with recipients of livers from non-DM donors (n = 138). The primary end-point included early post-transplant outcome, such as the incidence of primary nonfunction (PNF), hepatic artery thrombosis (HAT), and 90-day graft survival. Cox regression analysis was used to analyze the impact of donor DM on graft failure. PNF was observed in 5.8% of grafts from DM donors versus 2.9% of non-DM donor grafts (P = 0.31). Recipients of grafts derived from DM donors had a higher incidence of HAT (8.7% vs. 2.2%, P = 0.03) and decreased 90-day graft survival (88.4% [70.9–91.1] vs. 96.4% [89.6–97.8], P = 0.03) compared to recipients of grafts from non-DM donors. The adjusted hazard ratio for donor DM on graft survival was 2.21 (1.08–4.53, P = 0.03). In conclusion, donor DM is associated with diminished outcome early after liver transplantation. The increased incidence of HAT after transplantation of livers from DM donors requires further research.     

Technique of organ removal and fate of kidney grafts from liver donors.

The fate of 42 kidney grafts taken from heart-beating, ventilated donors at the same time as removal of the liver for allografting is reported, and is compared with 50 kidney grafts taken from heart-beating, ventilated donors whose ventilators were electively switched off either during or immediately before kidney removal. The fate of 32 kidney grafts taken from donors classified as "dead on arrival" at the admitting hospital is also reported. Onset of life-supporting graft function was significantly earlier among kidneys from the "liver donor" group. Consequently, immediate postoperative dialysis requirements were significantly less in recipients of this group of kidneys. Early graft survival, the incidence of graft primary nonfunction, failure of first and second kidney grafts, and recipient survival were not significantly different when comparing liver donor and "ventilator switch off" kidneys. No constant relationship was apparent in any donor group between graft fate and the anoxic and ischaemic times the graft was exposed to during organ removal and reimplantation.     

Hepatocellular ultrastructure after ischemia/reperfusion injury in human orthotopic liver transplantation

The number of patients requiring organ transplants still outpaces the number of available transplantable organs. During the process of orthotopic liver transplantation (OLTx), donor organs undergo significant stress resulting from ischemia and reperfusion. Healthy organs respond to this stressful environment with compensatory mechanisms that ideally allow for complete recovery. However, "marginal" organs do not compensate as well. Hepatic steatosis typically renders an organ nontransplantable; a liver with 30% or more fat has a 25% chance of primary nonfunction (PNF) or graft failure after a technically sound operation. In this study, we report on the significant markers of cellular ultrastructural change in steatotic livers. These include glycogen content, mitochondrial swelling, and hepatocellular blebbing. The data disclosed here argue that further investigation of these factors in marginal organs subjected to I/R may better facilitate our understanding of PNF.     

Gentle organ manipulation during harvest as a key determinant of survival of fatty livers after transplantation in the rat

Both in situ organ manipulation during harvest and steatosis reduce survival after liver transplantation via mechanisms involving Kupffer cells; thus, their effect on survival was compared here. Moderate steatosis was induced by a single dose of ethanol to Lewis rats, while long-term administration of ethanol yielded severe steatosis in donor animals. After minimal dissection during the first 12 min, livers were either manipulated gently or left alone for 13 min subsequently. Orthotopic liver transplantation was performed after 1 h of cold storage in UW solution. Ethanol increased hepatic lipid content to a level of moderate or severe steatosis that reduced survival after transplantation from 100 % to approximately 70 % (P < 0.05). However, gentle manipulation decreased survival to approximately 30 % (P < 0.05) in livers from normal, saline-treated rats and in livers from rats fed a high-fat control diet. Moreover, after short- or long-term ethanol administration, manipulation of fatty livers decreased survival from 70 % to approximately 13 % (P < 0.05). Further, manipulation elevated serum transaminases, total bilirubin, and necrosis significantly about 2- to 20-fold in fatty grafts after transplantation. At the end of harvest, trypan blue distribution time and hypoxia assessed from 2-nitroimidazole binding were elevated significantly about two- to fourfold by manipulation of fatty grafts. Gadolinium chloride, a Kupffer cell toxicant, blocked the detrimental effects of manipulation. These data demonstrate for the first time that, while steatosis is detrimental for survival, organ manipulation plays a much greater role than fat in mechanisms of primary nonfunction. Received: 28 September 1998 Received after revision: 29 April 1999 Accepted: 12 July 1999     

Non–heart-beating donors (then) and donation after cardiac death (now)

In the 1960s and 1970s, before the acceptance of brain death, donated organs were obtained from non–heart-beating donors. Today, this type of donor is referred to as a donor after cardiac death (DCD). After the acceptance of brain death criteria, most of the organs for transplantation were obtained from heart-beating donors. However, because of the shortage of brain-dead heart-beating donors in the 1980s, Maastricht surgeons started using organs obtained from DCD. Subsequently, they defined 4 different categories of non–heart-beating donors. In the United States, DCD donation has only recently gained widespread use. In this article, we present a historical overview of DCD donation; examine current practices for organ preservation and outcomes for kidney, kidney-pancreas, liver, and lung transplantation performed using organs obtained from DCD donors; and reported to the Organ Procurement and Transplantation Network/United Network for Organ Sharing database.     

Quantification of Degree of Steatosis in Extended Criteria Donor Grafts With Standardized Histologic Techniques: Implications for Graft Survival

The gap between the availability of livers from organ donors and the increased demand has led many centers to apply strategies to reduce this deficit. Splitting of cadaveric organs for use in 2 recipients; domino transplantation; and organs from living donors, non-heart-beating donors, and extended-criteria donors (ECDs) are all currently used in orthotopic liver transplantation (OLT). Fatty changes in the donor liver are a risk factor for poor function after OLT; however, the presence of steatosis, frequently present in livers from ECDs, does not exclude the use of these organs. Since January 2000 at our institution, we observed 39 steatotic grafts that were stratified istologically as follows: low steatosis, 5% to 15%; mild steatosis, 16% to 30%; moderate steatosis, 31% to 60%; and severe steatosis (>60%). Histologic techniques can enable identification of the type of fatty change as macrovesicular and microvesicular. These alterations have different effects on primary nonfunction and primary dysfunction. Fifteen grafts, all with severe or moderate, macrovesicular changes were discarded. Twenty-four fatty grafts with low to moderate steatosis were utilized for transplant. Sections from 2 liver biopsies (1 wedge in the left lobe and 1 needle in the right lobe) were stained with hematoxylin-eosin, Masson trichrome, Gomori reticulin, and oil red O. The OLT was performed only in patients with a MELD (Model for End-Stage Liver Disease) score lower than 27. The rate of primary dysfunction was 12.5%, and of primary nonfunction 8.4%. The 6-month graft survival for all fatty livers was 80%. We encourage the careful use of grafts with low to moderate steatosis in recipients without additional risks.     

Steatotic liver transplantation in the mouse: a model of primary nonfunction

BACKGROUND: The number of potential donor organs deemed suboptimal for transplantation because of hepatic steatosis is rising as the obesity rate increases. However, no mouse transplant model has been described within the framework of hepatic steatosis. We describe the development of and our initial experience with a steatotic mouse orthotopic liver transplant model using the ob/ob mouse. This model is technically achievable and functionally mimics primary nonfunction. MATERIALS AND METHODS: Adapting techniques of a nonarterialized murine transplant model, C57BL6 ob/ob mice aged 5-7 weeks (26-35 g) and lean controls served as liver donors and recipients. Orthotopic liver transplantation (OLT) was performed using a two-cuff technique at the infrahepatic cava and portal vein. The suprahepatic cava was anastomosed end to end, and the bile duct was stented. The hepatic artery was not reconstructed. RESULTS: Lean-to-lean OLT was performed with 70% (n = 10) long-term survival. ob/ob-to-age-matched lean recipients had 0% (n = 10) survival because of size discrepancy. ob/ob livers were transplanted to size-matched lean recipients (>3 months old) with short-term survival of 30% (n = 10). These mice survived the operation, awakened, but expired within 24 h. Serum transaminases revealed a significantly higher injury profile in the recipients of the steatotic livers, and histology showed massive centrilobular coagulative necrosis with hemorrhage, the overall picture being that of primary nonfunction. CONCLUSIONS: This novel use of the ob/ob mouse for OLT provides us with a model for steatotic transplantation with primary nonfunction as the end point and may help to better understand the response of the steatotic liver to the insult of transplantation.     

Long-term outcome of controlled, non-heart-beating donor liver transplantation

BACKGROUND: Previous reports have established the feasibility of using livers from controlled, non-heart-beating donors (CNHBD) with good immediate graft function. This has been largely borne out of necessity because of the donor shortage. METHODS: Retrospective database review for the last 7 years (1995-2002), encompassing 19 patients receiving CNHBD, with follow-up period of 1,000 +/- 694 days, median 762 days. Detailed review of recipient characteristics, operative and clinical course, immunosuppression, complications, survival rates, and comparison with the results obtained in patients receiving transplants of allografts procured in standard fashion, from heart-beating donors RESULTS: Kaplan-Meier patient survival rates were 100%, 89.5%, and 83.5% at 30 days, 1, and 2 years, respectively, which is not different from recipients of livers procured from heart-beating cadaveric donors (P=0.74, log-rank test). Five patients died at a mean follow-up time of 492 (range 46-1,103) days. The causes of death were related to secondary sclerosing cholangitis (n=1), cardiac failure (n=1), and sepsis (n=3). Two (10.5%) recipients underwent retransplantation, one for primary graft nonfunction and one because of biliary cast syndrome with cholangitis. Significant preservation damage (ALT>2,000) developed in five patients, but this did not affect survival. The incidence of vascular (15.6% vs. 9.6%, P=0.34) and biliary complications (10.55 vs. 13.8%, P=0.68) was no different than for those recipients receiving standard cadaveric donors. CONCLUSIONS: CNHBD safely expands the donor pool with similar long-term results as those obtained in patients receiving organs from brain-dead donors under standard procurement techniques.