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Workgroup on expanded criteria organs for liver transplantation (Special Article)
... Currently, there are a large number of predictive models for graft failure, all of which are heterogeneous because they use different criteria to select the independent variables. In general, the models have the same goal, which is to predict the development of liver dysfunction and provide an evidence-based tool that is useful during the liver graft selection process [3][4][5] . To ensure proper function of a liver graft, the hepatocellular critical mass is needed to maintain synthetic function and adequate blood supply through the vascular tree. ...
BACKGROUND Despite being the world's most widely used system for staging and therapeutic guidance in hepatocellular carcinoma (HCC) treatment, the Barcelona clinic liver cancer (BCLC) system has limitations, especially regarding intermediate-grade (BCLC-B) tumors. The recently proposed Hong Kong liver cancer (HKLC) staging system appears useful but requires validation in Western populations. AIM To evaluate the agreement between BCLC and HKLC staging on the management of HCC in a Western population, estimating the overall patient survival. METHODS This was a retrospective study of HCC patients treated at a university hospital in southern Brazil between 2011 and 2016. Demographic, clinical, and laboratory data were collected. HCC staging was carried out according to the HKLC and BCLC systems to assess treatment agreement. Overall survival was estimated based on the treatment proposed in each system. RESULTS A total of 519 HCC patients were assessed. Of these, 178 (34.3%) were HKLC-I; 95 (18.3%) HKLC-IIA; 47 (9.1%) HKLC-IIB; 29 (5.6%) HKLC-IIIA; 30 (5.8%) HKLCIIIB; 75 (14.4%) HKLC-IV; and 65 (12.5%) HKLC-V. According to the BCLC, 25 (4.9%) were BCLC-0; 246 (47.4%) BCLC-A; 107 (20.6%) BCLC-B; 76 (14.6%) BCLCC; and 65 (12.5%) BCLC-D. The general agreement between the two systems was 80.0% - BCLC-0 and HKLC-I (100%); BCLC-A and HKLC-I/HKLC-II (96.7%); BCLC-B and HKLC-III (46.7%); BCLC-C and HKLC-IV (98.7%); BCLC-D and HKLC-V (41.5%). When sub-classifying BCLC-A, HKLC-IIB, HKLC-IIIA and HKLC-IIIB stages according to the up-to-7 in/out criterion, 13.4, 66.0, 100 and 36.7%, respectively, of the cases were classified as up-to-7 out. CONCLUSION In a Western population, the general agreement between the two systems was 80.0%, although in BCLC-B cases the agreement was low, suggesting that some individuals could be candidates for the curative treatment recommended by the HKLC. The authors suggest that the BCLC system should be routinely employed, although for BCLC-B cases it should be associated with the HKLC system.
... In general, despite an increase in delayed graft function (DGF), long-term graft function of the older allograft and patient survival are acceptable when compared to SCDs, and mortality decreased when compared to those on the waiting list, thereby justifying the use of such organs [5]. In a recent consensus meeting on liver transplantation, the ideal donor was defined according to the following criteria: trauma as the cause of death, donation after brain death, age below 40 years, hemodynamic stability at the time of procurement, no steatosis or any other underlying chronic liver lesion, and no transmissible disease [6, 7]. Certainly the elderly liver donor would has a significant impact on allograft function as advanced age have been attributed to a liver with impaired regenerative capacity and an increased severity of hepatitis C virus (HCV) recurrence. ...
At the time of the writing of this chapter the number of candidates on the waiting list, as designated by the United Network for Organ Sharing (UNOS), totals just over 100,000 [1]. A closer look at yearly tabulations of patients transplanted and patients newly listed shows that for about every two patients added to the transplant list, one patient is actually transplanted. Because the waiting list continues to grow, there has been increased interest in the use of expanded criteria donors (ECD). While there are many different ways to define the ECD, one universal attribute of ECD that makes it germane to the topic of this textbook is increased donor age. The aims of this chapter are to (1) examine the elderly donor evaluation and screening process in this patient population; (2) discuss the predonation management of these older patients as well as the donor procedure and technical complications that may be encountered in the procurement operation, and (3) discuss the allocation process and examine the results and outcomes in the use of these elderly organs.
... Our center has reported that transplantation of ECD livers improved patient survival and showed that the use of these marginal liver grafts maximizes donor utilization and increased access to liver transplantation [10]. Barshes et al. also demonstrated that using ECD livers as defined by the New York State Department of Health Workgroup significantly reduced waiting list mortality [11,12]. As such, there has been a shift toward greater use of ECD livers. ...
As the rate of medically suitable donors remains relatively static worldwide, clinicians have looked to novel methods to meet the ever-growing demand of the liver transplant waiting lists worldwide. Accordingly, the transplant community has explored many strategies to offset this deficit. Advances in technology that target the ex vivo "preservation" period may help increase the donor pool by augmenting the utilization and improving the outcomes of marginal livers. Novel ex-vivo techniques such as hypothermic, normothermic and subnormothermic machine perfusion may be useful to "resuscitate" marginal organs by reducing ischemia/reperfusion injury. Moreover, other preservation techniques such as oxygen persufflation are explored as they may also have a role in improving function of "marginal" liver allografts. Currently, marginal livers are frequently discarded or can relegate the patient to early allograft dysfunction and primary non-function. Bench to bedside advances are rapidly emerging and hold promise for expanding liver transplantation access and improving outcomes.
... This is not surprising as the MELD score was developed to predict outcome of relatively noninvasive Transjugular Intrahepatic Portosystemic Shut (TIPS) procedures based on intrinsic liver disease [11] but does not account for important factors that are critical to the success of the transplant operation that are not predicted by candidate characteristics alone. For example, donor factors, such as age, race, gender, degree of steatosis, cause of death, ischemia time, have all been documented to play a role in patient and graft survival [12][13][14][15][16]. As these factors are independent of candidate MELD score at the time of organ offer and some degree of physician judgment (behavior) will determine whether some or all of these donor risk factors will be incorporated into the over risk profile for a given recipient with a given MELD score, it is understandable why the MELD score alone does not predict post-LT outcome. ...
Background:
Liver transplantation has been demonstrated to be the best treatment for several liver diseases, while grafts are limited. This has caused an increase in waiting lists, making it necessary to find ways to expand the number of organs available for transplantation. Normothermic perfusion (NMP) of liver grafts has been established as an alternative to static cold storage (SCS), but only a small number of perfusion machines are commercially available.
Methods:
Using a customized ex-situ machine perfusion, we compared the results between ex-situ NMP and SCS preservation in a porcine liver transplant model.
Results:
During NMP, lactate concentrations were 80% lower after the three hours perfusion period, compared with SCS. Bile production had a 2.5-fold increase during the NMP period. After transplantation, aspartate transaminase (AST) and alanine transaminase (ALT) levels were 35% less in the NMP group, compared to the SCS group. In pathologic analyses of grafts after transplant, tissue oxidation did not change between groups, but the ischemia-reperfusion injury score was lower in the NMP group.
Conclusion:
NMP reduced hepatocellular damage and ischemia-reperfusion injury when compared to SCS using a customized perfusion machine. This could be an alternative for low-income countries to include machine perfusion in their therapeutic options.
Donor-derived transmission of infectious diseases is a well-recognized complication of solid organ transplantation. The rate of disease transmission from donors to recipients and the effectiveness of current donor screening protocols are unknown. Most donor-derived disease transmissions are expected. Although uncommon, unexpected donor-derived infections can be associated with significant morbidity and mortality, and as the volume of patients undergoing solid organ transplantation increases, the number of infections transmitted through organ donation can also be expected to rise. Accurate reporting of transmission events is limited by difficulty in recognizing potential events and in distinguishing allograft derived from recipient-derived diseases. Donor screening protocols have been designed to reduce the likelihood that organs would transmit infection or malignancies while enhancing availability. Such protocols merit continuous evaluation in the face of either new scientific data or new microbiological assays. The growing gap between the number of patients waiting for transplantation and available organs continues to be the number one issue facing the transplant community. As a consequence, the major focus in organ transplantation has been developing strategies to increase the available organs, including the use of organs from donors with infections or risky behaviors that have disqualified them from the donation in the past.
Liver transplantation is the final treatment option for end-stage liver disease and acute liver failure, although availability of donor organs is a major limitation. The large gap between the growing list of patients awaiting liver transplantation and the scarcity of donor organs has fueled efforts to maximize the existing donor pool and identify new avenues. We treated a 13-year-old boy who had acute liver failure, due to Wilson's disease, with transplantation of a liver from a deceased liver donor with a calcified hydatid cyst. After 3 years of follow-up, liver function tests remained normal, hydatid cyst serology was negative, and no hydatid cyst or other problems were observed.
Aim
This study investigated whether ischemic postconditioning (IPO) improved the outcome of organs from donors after cardiac death and had a synergistic effect with hypothermic machine perfusion (HMP) in a pig liver transplantation model.
Methods
A donor after cardiac death (DCD) model was developed in 48 healthy Bama miniature pigs randomly divided into 4 groups: simple cold storage group (SCS group), IPO group, HMP group, HMP–IPO group. The levels of serum alanine aminotransferase (ALT), total bilirubin, histopathological findings, apoptotic activity of hepatocytes, international normalized ratio (INR), tumor necrosis factor-α (TNF-α), and Malondialdehyde (MDA) were compared.
Results
All recipients in the SCS group died within 6 h after transplantation. The livers of the recipients in the IPO had 50% survival on day 5. HMP allowed 83.3% survival and HMP–IPO allowed 100% survival. After reperfusion, the recipients in the IPO and HMP–IPO group had lower ALT and total bilirubin levels, less Suzuki score, less apoptosis, and less injury to hepatocytes and biliary ducts and attenuated inflammatory response and oxidative load.
Conclusions
IPO improved the outcome of organs from donors after cardiac death and had a synergistic effect with HMP in the pig liver transplantation model.
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INTRODUCTION. Nowadays, the highest limitation of transplantation is the lack of donors with an increase of the figure of patients that die waiting for an organ. The main objective of the study was to know the distribution of donors in the country and why organs were not extracted in some cases. METHODS. A descriptive longitudinal, prospective and observational study of the donation-organ extraction process was conducted in 87 cadaveric donors with encephalic death and beating heart that were given to the Multiorgan Extraction Group of the Medicosurgical Research Center by the National Transplant Coordinating Office between 2002 and 2005. RESULTS. Havana City, Camagüey and Holguin were the provinces with the highest number of donors. The most frequent causes of encephalic death were cerebrovascular accident (43 cases) and cranial traumas (33 patients). The patients stayed less than 3 days at the intensive care unit as potential donors. Multiple organ extraction was possible in 78 of the 87 alerts received (90 %). Family refusal was the most common cause of the non-extraction of organs. CONCLUSIONS. It is very important to take care of the donors at the intensive care units and to match over the adequate treatment of the family.
Background:
The utilization of liver transplantation (LT) is limited by the availability of suitable organs. This study aimed to assess the impact of the donor risk index (DRI) and other donor characteristics on fibrosis progression, graft, and patient survival in hepatitis C virus (HCV)-infected LT recipients.
Methods:
HCV-infected LT recipients who had at least 2 post-LT protocol liver biopsy specimens available were included. Hazard ratio for bivariate analysis was computed using Cox proportional hazard regression analysis.
Results:
Of 312 recipients, 26.6% died over a median follow-up of 58.5 months (95% CI: 46.5-67.3). Fourteen patients underwent re-transplantation. Mean time to graft failure was 84.3 months, median follow-up: 59 months, 95% CI (48.2, 68.3). DRI >1.5 was significantly associated with patient and graft survival (P = 0.04). Of the subset of 104 individuals who underwent histological analysis, 67.3% progressed to ≥F2. On multivariate analysis, significant donor-specific predictors of fibrosis progression were: donor age >50 years and DRI >1.7.
Conclusions:
(1) Fibrosis progression in HCV-infected LT recipients is strongly associated with donor characteristics, specifically donor age and DRI. (2) DRI, an objective measure of donor quality, appears to correlate both with rate of histological progression and overall patient/graft survival.
Reflective of the gross national shortage of organs available for transplantation, utilization of extended criteria donor livers has gained momentum, arguing the merits of transplantation with higher risk organs outweighs the risks associated with staying on the waiting list. As a result, high-risk extended criteria allografts, previously referred to as marginal or compromised organs, have become an important part of the donor organ supply. Unfortunately, the use of “expanded” criteria liver allografts remains undefined. Therefore, due to regional heterogeneity in the landscape of national scarcity, allocation policies for extended criteria allografts have largely been transplant center specific and calibrated based on predicted recipient benefit, projected reduction in waitlist mortality, and parity. The utility, selection, and performance of “extended criteria” donor allograft livers are examined in this review.
During the last couple of decades, with standardization and progress in surgical techniques, immunosuppression and post liver transplantation patient care, the outcome of liver transplantation has been optimized. However, the principal limitation of transplantation remains access to an allograft. The number of patients who could derive benefit from liver transplantation markedly exceeds the number of available deceased donors. The large gap between the growing list of patients waiting for liver transplantation and the scarcity of donor organs has fueled efforts to maximize existing donor pool and identify new avenues. This article reviews the changing pattern of donor for liver transplantation using grafts from extended criteria donors (elderly donors, steatotic donors, donors with malignancies, donors with viral hepatitis), donation after cardiac death, use of partial grafts (split liver grafts) and other suboptimal donors (hypernatremia, infections, hypotension and inotropic support).
Much of the success of a transplant depends on appropriate matching of donor to recipient.
We validated the Donor Risk Index formula (DRI) using Mount Sinai Medical Center's 10-year cohort of over 1000 transplants.
The DRI was significantly associated to graft failure with a relative risk (RR) of 1.32. Our cohort had an average DRI of 2.6 with survival of 83% at 3 months, 79% at 1 year, and 70% at 3 years. The low rate of graft failure at a high DRI implies that there are other factors important in transplant pairing that are not considered in the DRI model. To determine these variables and quantify their importance, we constructed a Transplant Risk Index by identifying recipient and donor variables not captured in United Network for Organ Sharing (UNOS) that significantly correlated to graft failure. The most significant independent predictors of time to graft failure were donor age, weight, and peak serum sodium; ischemia time; and recipient creatinine, international normalized ratio, and hepatitis C infection. The coefficients for each of these factors were compiled into a Transplant Risk Index formula. A cutoff of 5 resulted in a graft survival rate of 86% at 3 months, 76% at 1 year, and 62% at 3 years using Kaplan-Meier analysis. The predictive ability of the Transplant Risk Index was greater than the DRI or DMELD (the product of donor age and preoperative MELD) as assessed by the area under the receiver operating curve and the positive and negative predictive values.
The Transplant Risk Index captures recipient factors and donor factors not captured in UNOS. Including these factors may improve the ability to predict good donor-recipient pairing.
The number of patients suitable for liver transplantation is progressively increasing due to the excellent results achieved with this procedure, giving rise to a growing imbalance in the number of candidates on the waiting list and the number of donors. This situation has prompted transplant teams to search for alternatives to increase the number of liver grafts. On the one hand, the criteria for donation have been broadened to include donors with advanced age, liver steatosis, hepatitis B and C viruses, neoplasms, and benign underlying diseases. On the other hand, new transplant techniques have been used with grafts from split livers, living donors, sequential or domino transplants and non-heart-beating donors. Other options such as xenotransplantation and hepatocyte transplants currently lack clinical applicability.
The aim of this study was to critically analyze the early and long-term results of a newborn liver transplantation (LTx) centre using piggyback technique (PT) without venovenous bypass and portocaval shunt in the era of extended criteria donors (ECDs). Between 2002 and 2010, a total of 229 LTx were performed in 225 patients, with the shortest as possible cold ischemia time (CIT) policy. The charts of the donors and recipients and the intraoperative data were retrospectively reviewed in order to define the feasibility of PT and surgical outcome, and long-term graft and patient survival. PT feasibility rate was 100%, with a median duration of surgery of 390 min (range 210-630) and median unit of packed RBC transfused intraoperatively of 1 U (range 1-10). Median CIT was 400 min (range 130-870), and median AST peak was 403 mmol/L (range 48-16,900). ECDs graft rate was 85%. Over all primary dysfunction and non-function (PNF) rates were 7.4 and 2.2%, respectively and increased with graft steatosis >30% (P < 0.004). Mortality, morbidity, re-operation and re-LTx rates were 4.4, 25, 6.1 and 1.3%, respectively, and median hospital stay was 18 days (range 8-150). On the long term, graft and patient 5-year overall survival were 72 and 74%, respectively, and re-LTx rate was 0.4%. Survival was significantly affected by recipient HCV-Ab seropositive status (67 vs. 85%, P = 0.023). Liver transplantation can be performed with low morbidity and mortality rates, despite ECDs. PT is a safe and effective procedure that, combined with short CIT, entailed prompt early functional recovery of the grafts and positive long-term results.
A growth in the utilization of high-risk allografts is reflective of a critical national shortage and the increasing waiting list mortality. Using risk-adjusted models, the aim of the present study was to determine whether a volume-outcome relationship existed among liver transplants at high risk for allograft failure.
From 2002 to 2008, the Scientific Registry of Transplant Recipients (SRTR) database for all adult deceased donor liver transplants (n = 31 587) was queried. Transplant centres (n = 102) were categorized by volume into tertiles: low (LVC; 31 cases/year), medium (MVC: 64 cases/year) and high (HVC: 102 cases/year). Donor risk comparison groups were stratified by quartiles of the Donor Risk Index (DRI) spectrum: low risk (DRI ≤ 1.63), moderate risk (1.64 > DRI > 1.90), high risk (1.91 > DRI > 2.26) and very high risk (DRI ≥ 2.27).
HVC more frequently used higher-risk livers (median DRI: LVC: 1.82, MVC: 1.90, HVC: 1.97; P < 0.0001) and achieved better risk adjusted allograft survival outcomes compared with LVC (HR: 0.90, 95%CI: 0.85-0.95). For high and very high risk groups, transplantation at a HVC did contribute to improved graft survival [high risk: hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.76-0.96; Very High Risk: HR: 0.88, 95%CI: 0.78-0.99].
While DRI remains an important aspect of allograft survival prediction models, liver transplantation at a HVC appears to result in improved allograft survival with high and very high risk DRI organs compared with LVC.
Reflective of the gross national shortage of organs available for transplantation, utilization of high-risk donor livers has gained momentum. Despite these demands, many marginal livers are discarded annually. Our study evaluated the impact of center volume on survival outcomes associated with liver transplants utilizing high donor risk index (DRI) allografts. METHODS:
We queried the SRTR database for deceased donor liver transplants (n=31,587) among recipients ≥18 years old from 2002-2008, and excluded partial and multiple-liver transplants. A high-DRI cohort (n=15,668), defined as DRI >1.90, was analyzed separately. Transplant centers (n=102) were categorized into tertiles by annual procedure volumes: High (HVC: 78-215 cases/year), Medium (MVC: 49-77 cases/year) and Low (LVC: 5-48 cases/year). Endpoints were allograft and recipient survival. RESULTS:
Compared to their lower volume counterparts, HVC utilized donors with higher mean DRI (HVC: 2.07, MVC: 2.01, LVC: 1.91), ≥60 years of age (HVC: 18.02%, MVC: 16.85%, LVC: 12.39%), deceased following stroke (HVC: 46.53%, MVC: 43.71%, LVC: 43.36%) and donation after cardiac death (HVC: 5.04%, MVC: 4.53%, LVC: 3.50%; all p CONCLUSION:
High volume centers more frequently utilized higher DRI livers and achieved better risk-adjusted allograft and recipient survival. Further understanding of outcomes following use of high DRI livers may improve utilization, post-operative outcomes and potentially future allocation practices. Liver Transpl, 2011. © 2011 AASLD.
Copyright © 2011 American Association for the Study of Liver Diseases.
We examined the UNOS database from 7/15/00-7/17/05 for Regional deceased donor liver utilization. For each region, we performed logistic regression and derived odds ratios (OR) for donor characteristics associated with livers being transplanted outside of the region or not transplanted at all. Regions with smallest and least significant OR were considered aggressive users of suboptimal organs. We estimated how many untransplanted livers from less aggressive regions might be used by more aggressive regions. Only Region 9 was significantly more aggressive than others (median OR: 6 vs. 16; p < 0.01; median OR size: 1.4 vs. 3.6; p < 0.01). Region 9 transplanted at higher median Model for End-stage Liver Disease (MELD) score (20.4 [6-73] vs. 18.3 [6-70], p < 0.01), but had the lowest one- and five-yr graft survival (p < 0.01). Of 30,474 livers, 5056 were not transplanted, of which 3690 were procured outside Region 9 but met Region 9 use criteria. Of these, 1488 and 1807 livers had donor risk indices ≤ 2, for hypothetical 12 and 8 h cold ischemia time (CIT), respectively. Regional differences in liver utilization are profound. Region 9 is significantly more aggressive. At the most, 297-361 organs per year may have been used under Region 9's use criteria but overall graft survival may have declined.
Because of organ shortage and a constant imbalance between available organs and candidates for liver transplantation, expanded criteria donors are needed. Experience shows that there are wide variations in the definitions, selection criteria, and use of expanded criteria donors according to different geographic areas and different centers. Overall, selection criteria for donors have tended to be relaxed in recent years. Consensus recommendations are needed. This article reports the conclusions of a consensus meeting held in Paris in March 2007 with the contribution of experts from Europe, the United States, and Asia. Definitions of expanded criteria donors with respect to donor variables (including age, liver function tests, steatosis, infections, malignancies, and heart-beating versus non-heart-beating, among others) are proposed. It is emphasized that donor quality represents a continuum of risk rather than "good or bad." A distinction is made between donor factors that generate increased risk of graft failure and factors independent of graft function, such as transmissible infectious disease or donor-derived malignancy, that may preclude a good outcome. Updated data concerning the risks associated with different donor variables in different recipient populations are given. Recommendations on how to safely expand donor selection criteria are proposed.
Although priority for liver transplantation is determined by the model for end-stage liver disease (MELD) score, the quality of organs used is subject to physician discretion. We aimed to determine whether implementation of MELD affected the quality of organs transplanted, the type of patients who receive the higher-risk organs, and the impact of these changes on their posttransplant survival.
Data were analyzed from the United Network for Organ Sharing of adults who underwent deceased-donor liver transplantation between January 1, 2007, and August 1, 2007 (n = 47,985). Dependent variables included the donor risk index (a continuous variable that measures the risk of graft failure associated with a particular organ) and patient survival after transplantation.
The overall organ quality of transplanted livers has worsened since MELD implementation, with an increase in the donor risk index equivalent to a 4% increased risk of graft failure after adjusting for temporal trends (P < .001). This was accompanied by a shift from using the higher-risk organs in the more urgent patients (in the pre-MELD era) to using the higher-risk organs in the less urgent patients (in the post-MELD era). Posttransplant survival has worsened over time (hazard ratio, 1.017/y; P = .005) among the less urgent patients (MELD scores, <20); mediation analysis suggests this change in survival was caused primarily by changes in organ quality.
As an unintended consequence of the MELD allocation policy, patients that are least in need of a liver transplant now receive the highest-risk organs. This has reduced posttransplant survival in recent years among patients with low MELD scores.
A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care.
This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues.
When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States.
Continued progress in organ donation will help enable transplantation to alleviate the increasing incidence of end-stage organ disease. This article discusses the implementation and effect of the federally initiated Organ Donation Breakthrough Collaborative; it then reviews organ donation data, living and deceased, from 1995 to 2004. It is the first annual report of the Scientific Registry of Transplant Recipients to include national data following initiation of the collaborative in 2003. Prior to that, annual growth in deceased donation was 2%-4%; in 2004, after initiation of the collaborative, deceased donation increased 11%. Identification and dissemination of best practices for organ donation have emphasized new strategies for improved consent, including revised approaches to minority participation, timing of requests and team design. The number of organs recovered from donation after cardiac death (DCD) grew from 64 in 1995 to 391 in 2004. While efforts are ongoing to develop methodologies for identifying expanded criteria donors (ECD) for organs other than kidney, it is clear DCD and ECD raise questions regarding cost and recovery. The number of living donor organs increased from 3493 in 1995 to 7002 in 2004; data show trends toward more living unrelated donors and those providing non-directed donations.
Extended-donor criteria liver allografts do not meet traditional criteria for transplantation. Although these organs offer immediate expansion of the donor pool, transplantation of extended-donor criteria liver allografts increases potential short- and long-term risk to the recipient. This risk may manifest as impaired allograft function or donor-transmitted disease. Guidelines defining this category of donor, level of acceptable risk, principles of consent, and post-transplantation surveillance have not been defined. This article reviews the utilization, ethical considerations, and outcomes of extended-donor criteria liver allografts.
Deceased donor factors associated with poor graft outcome are well known, but how often these factors lead to livers left untransplanted is poorly defined. A nested, case-control study was conducted using the United Network for Organ Sharing (UNOS) database from 1987 to 2005. Only those donating >/=1 solid organ were included. Primary outcome was livers not transplanted (LNT, cases) versus transplanted (LT, controls). Primary variables for multivariate analysis were donor age and obesity. Covariates included donation after cardiac death (DCD), cerebral vascular accident death, viral serologies, cancer, ALT and bilirubin. There were 23 373 (26%) LNT's from 91 362 donors who donated at least one organ. Percent LNT fell over time (1987-1990: 48%; 1991-1995: 29%; 1996-2000: 21%; 2000-2005: 16%; p < 0.01). Increased age (odds ratio: 4.2, 95% confidence interval 3.6-4.9, p < 0.01) and obesity (2.1, 1.9-2.3, p < 0.01) were significantly associated with LNT across all time periods. Other significant factors included DCD and elevated ALT. For 2001-2005, population attributable risk indicate that age >40, abnormal ALT and obesity account for 32.6%, 25.3% and 9.2% of untransplanted livers, respectively. Use of expanded criteria livers has pushed LNT lower in spite of an aging and heavier donor population. Nevertheless, age and obesity still account for a significant portion of untransplanted livers.
Extended criteria donor (ECD) liver allografts are often allocated to less severely ill liver transplant (LT) candidates who are at a relatively lower risk of pretransplant mortality, but it is not clear that the use of ECD allografts will decrease center waitlist mortality (WLM). Individual patient data from the UNOS OPTN database (2002-2005) were aggregated to obtain center-specific data. Deceased donor allografts with any of the following characteristics were defined as ECDs: from a donor with any of the criteria described by the New York State Department of Health Workgroup; or 12+ h of cold ischemia. Multivariate regression was used to examine the relationship between WLM and ECD, non-ECD and LDLT use after adjusting for candidate severity of illness. A total of 3555 ECD transplants, 11,660 standard criteria donor (SCD) transplants, and 717 LDLTs were performed at 100 centers during this period. The model demonstrated that SCD and ECD LTs were inversely correlated with a center's WLM (beta=-0.242 and -0.221, respectively; p <or= 0.003 for each). LDLTs did not significantly reduce WLM (beta=-0.048, p=0.55). In summary, increasing ECD liver allograft use significantly decreased WLM at US centers. Policies encouraging the increase used of ECDs would further reduce WLM.
Among the challenges in liver transplantation, the limits of patient access to transplantation continue to drive a broad range of research and innovation. In contrast, continued improvements in immunosuppression over the past decade have dramatically reduced the consequences of rejection such that recurrent disease, in particular HCV and HCC, and comorbid conditions are now the largest threat to the long-term survival of transplant recipients. Scarcity of organs has sharpened the impetus to select for transplantation those patients who are most likely to benefit from the transplant and least likely to be harmed by the process. The MELD has assisted physicians in prognosticating and choosing the most appropriate candidates for transplantation. LDLT necessitates a distinct workup from deceased donor liver transplantation and requires unique consideration of timing of the transplantation. Recurrent HCV and optimal management of patients with HCC continue to challenge transplant hepatologists and gastroenterologists caring for transplant candidates and recipients.
Availability of cadaveric kidneys for transplantation is far below the growing need, leading to longer waiting time and more deaths while waiting.
Using national data from 1995 to 2000, we evaluated graft survival by donor characteristics and the rate of discard of retrieved organs, with the goal of increasing use of kidneys that are associated with increased risk of graft failure, that is, expanded donor kidneys.
Cox models identified four donor factors that independently predicted significantly higher relative risk of graft loss compared with a low-risk group. These factors included donor age, cerebrovascular accident as the cause of death, renal insufficiency (serum creatinine >1.5 mg/dL), and history of hypertension. Expanded donor kidneys were defined as those with relative risk of graft loss greater than 1.70 and included all donors aged 60 years and older and those aged 50 to 59 years with at least two of the other three conditions (cerebrovascular cause of death, renal insufficiency, hypertension). The expanded donor group accounted for 14.8% of transplanted kidneys. Among organs procured from expanded donors, 38% were discarded versus 9% for all other kidneys. The risk of graft loss of expanded donor kidneys was increased in both older and younger recipients but to a greater extent in those recipients older than 50 years.
By identifying donor factors associated with graft failure, these analyses may help to expand the number of transplanted kidneys by increasing the utilization of retrieved cadaveric kidneys.
Medical Director of Liver Transplantation
- Md Gordon
Gordon, MD, Medical Director of Liver Transplantation,
Lahey Clinic Medical Center, Burlington, MA; Richard D.
MD, Professor of Surgery and Pediatrics, Director, Adult and Pediatric Liver Transplant Programs, Mount Sinai Hospital Assistant Professor of Surgery
- Richard B Freeman
Medicine, Professor of Bioethics, Department of Epidemiology and Social Medicine, Montefiore Medical Center,
Bronx, NY; Sukru Emre, MD, Professor of Surgery and Pediatrics, Director, Adult and Pediatric Liver Transplant Programs, Mount Sinai Hospital, New York, NY; Sandy Feng,
MD, PhD, Assistant Professor of Surgery, Department of
Surgery, University of California, San Francisco, CA; Richard
B. Freeman, Jr., MD, Professor of Surgery, Tufts University
School of Medicine, New England Medical Center, Division
of Transplant Surgery, Boston, MA; John J. Fung, MD, PhD,
Chairman, Department of General Surgery, Director, Transplant Center, Cleveland Clinic, Cleveland, OH; Fredric D.
Sukru Emre, MD, Professor of Surgery and Pediatrics, Director, Adult and Pediatric Liver Transplant Programs
- Richard B Freeman
Medicine, Professor of Bioethics, Department of Epidemiology and Social Medicine, Montefiore Medical Center,
Bronx, NY; Sukru Emre, MD, Professor of Surgery and Pediatrics, Director, Adult and Pediatric Liver Transplant Programs, Mount Sinai Hospital, New York, NY; Sandy Feng,
MD, PhD, Assistant Professor of Surgery, Department of
Surgery, University of California, San Francisco, CA; Richard
B. Freeman, Jr., MD, Professor of Surgery, Tufts University
School of Medicine, New England Medical Center, Division
of Transplant Surgery, Boston, MA;
Liver Transplantation and Hepatobiliary Surgery
- Patricia Ann Sheiner
- Director Md
Patricia Ann Sheiner,
MD, Director, Liver Transplantation and Hepatobiliary Surgery, Westchester Medical Center, Valhalla, NY; Lewis
Teperman, MD, Director of Transplantation; New York
University Medical Center, New York, NY;
Division of Transplantation, Healthcare Systems Bureau, Health Resources and Services Administration
- Carla Williams
- Hui-Hsing Wong
- J D Md
- Analysis Operations
- Branch
Carla Williams,
Executive Director, New York Center for Liver Transplantation, East Greenbush, NY; and Hui-Hsing Wong, MD, JD,
Operations and Analysis Branch, Division of Transplantation, Healthcare Systems Bureau, Health Resources and Services Administration, Rockville, MD. Other members of the
Workgroup from the New York State Department of Health
include: Antonia C. Novello, MD, MPH, Dr. PH, Commissioner, New York State Department of Health;
Director, Office of Health Systems Management; Lisa Wickens, RN, Assistant Director, Office of Health Systems Management
- Wayne Osten
Wayne Osten,
Director, Office of Health Systems Management; Lisa Wickens, RN, Assistant Director, Office of Health Systems Management;
Director of Clinical Affairs, Office of Health Systems Management
- Nancy Barhydt
- Dr
- Ph
- Rn
Nancy Barhydt, Dr. PH, RN, Director of Clinical
Affairs, Office of Health Systems Management;
Associate Attorney, Division of Legal Affairs
- Judy Doesschate
- Esq
Judy Doesschate, Esq., Associate Attorney, Division of Legal Affairs;
Bureau of Health Care Research, Information Services, Division of Health Care Standards and Surveillance
- Sherry Emrich
- Rn
Sherry Emrich, RN, Assistant Hospital Program Director/
Western Regional Office; Dawn Maynus, Program Research
Specialist III, Bureau of Health Care Research, Information
Services, Division of Health Care Standards and Surveillance;
Division of Health Care Standards and Surveillance; and Kimberly Valente, RN, Health Policy Associate, Bureau of Hospital and Primary Care Services, Division of Health Care Standards and Surveillance
- Lisa Mcmurdo
- Rn
- Director Mph
Lisa McMurdo, RN, MPH, Director, Division of Health
Care Standards and Surveillance; and Kimberly Valente, RN,
Health Policy Associate, Bureau of Hospital and Primary
Care Services, Division of Health Care Standards and Surveillance.
- Port