Kidney retransplantation from HLA‐incompatible living donors: A single‐center study of 3rd/4th transplants

Background

The demand for kidney retransplantation following graft failure is rising. Repeat transplantation is often associated with poorer outcomes due to both immunological and surgical challenges. The aim of this study was to compare surgical and functional outcomes of kidney retransplantation in recipients that had previously had at least two kidney transplants with a focus on those with antibody incompatibility.

Methods

We analyzed 66 patients who underwent renal transplantation at a single center between 2003 and 2011. Consecutive patients receiving their 3rd or 4th kidney were case‐matched with an equal number of 1st and 2nd transplants.

Results

Twenty‐two 3rd and 4th kidney transplants were matched with 22 first and 22 seconds transplants. Operative times and length of stay were equivalent between the subgroups. Surgical complication rates were similar in all groups (22.7% in 1st and 2nd transplants, and 27.2% in 3rd/4th transplants). There was no significant difference in patient or graft survival over 5 years. Graft function was similar between transplant groups at 1, 3, and 5 years.

Conclusions

Third and fourth kidney transplants can be performed safely with similar outcomes to 1st and 2nd transplants. Kidney retransplantation from antibody‐incompatible donors may be appropriate for highly sensitized patients.     

Pediatric Liver Transplant Recipients Who Undergo Transfer to the Adult Healthcare Service Have Good Long‐Term Outcomes

Liver transplantation has transformed survival for children with liver disease necessitating the transfer of a growing number of patients to the adult healthcare service. The impact of transfer on outcomes remains unclear. The aim of this single‐center study of 137 consecutive pediatric liver transplant recipients was to examine the effect of transfer on patient and graft survival. The median time from transplant to transfer was 10.4 years and the median age of the patients at transfer was 18.6 years. After transfer, there were 5 re‐transplants and 12 deaths in 14 patients. The estimated posttransfer 10‐year patient and graft survival was 89.9% and 86.2%, respectively. Overall, 4 patients demonstrated graft loss as a consequence of chronic rejection. Graft loss was associated with older age at first transplant (p = 0.008). When compared to young adult patients transplanted in the adult center, the transferred patients did not have inferior graft survival from the point of transfer (HR 0.28; 95% CI 0.10–0.77, p = 0.014). This suggests that transfer did not impact significantly on graft longevity. In conclusion, pediatric liver transplant recipients who undergo transfer to the adult service have good long‐term outcomes.     

Repeat Organ Transplantation in the United States, 1996–2005

The prospect of graft loss is a problem faced by all transplant recipients, and retransplantation is often an option when loss occurs. To assess current trends in retransplantation, we analyzed data for retransplant candidates and recipients over the last 10 years, as well as current outcomes. During 2005, retransplant candidates represented 13.5%, 7.9%, 4.1% and 5.5% of all newly registered kidney, liver, heart and lung candidates, respectively. At the end of 2005, candidates for retransplantation accounted for 15.3% of kidney transplant candidates, and lower proportions of liver (5.1%), heart (5.3%) and lung (3.3%) candidates. Retransplants represented 12.4% of kidney, 9.0% of liver, 4.7% of heart and 5.3% of lung transplants performed in 2005. The absolute number of retransplants has grown most notably in kidney transplantation, increasing 40% over the last 10 years; the relative growth of retransplantation was most marked in heart and lung transplantation, increasing 66% and 217%, respectively. The growth of liver retransplantation was only 11%. Unadjusted graft survival remains significantly lower after retransplantation in the most recent cohorts analyzed. Even with careful case mix adjustments, the risk of graft failure following retransplantation is significantly higher than that observed for primary transplants.     

Long-term results of liver transplantation in older patients 60 years of age and older

BACKGROUND: Advances in perioperative care and immunosuppression have enabled clinicians to broaden the indications for organ transplantation. Advanced age is no longer considered a contraindication to transplantation at most centers. Although short-term studies of elderly liver transplant recipients have demonstrated that the incidence of complications and overall patient survival are similar to those of younger adults, transplant center-specific, long-term data are not available. METHODS: From August of 1984 to September of 1997, 91 patients 60 years of age or older received primary liver transplants at the University of Wisconsin, Madison. This group of patients was compared with a group of younger adults (n=387) ranging in age from 18 to 59 years who received primary liver transplants during the same period. The most common indications for transplantation in both groups were Laennec's cirrhosis, hepatitis C, primary biliary cirrhosis, primary sclerosing cholangitis, and cryptogenic cirrhosis. There was no difference in the preoperative severity of illness between the groups. Results. The length of hospitalization was the same for both groups, and there were no significant differences in the incidence of rejection, infection (surgical or opportunistic), repeat operation, readmission, or repeat transplantation between the groups. The only significant difference identified between the groups was long-term survival. Five-year patient survival was 52% in the older group and 75% in the younger group (P<0.05). Ten-year patient survival was 35% in the older group and 60% in the younger group (P<0.05). The most common cause of late mortality in elderly liver recipients was malignancy (35.0%), whereas most of the young adult deaths were the result of infectious complications (24.2%). CONCLUSION: Although older recipients at this center did as well as younger recipients in the early years after liver transplantation, long-term survival results were not as encouraging.     

单个移植中心连续4000例肝移植后长期生存情况回顾

目的：评价大样本肝移植病人长期生存情况和分析影响移植疗效的动静因素。背景回顾：自1983年以来肝移植被接受为治疗终末期肝病的主要选择之一，随着免疫抑制剂的发展，手术技术的不断完善，取肝及保存方法改进，生存期获不断延长。虽然报告影响近期生存因素的文章甚众，但分析影响长期生存因素者却不多见。方法：回顾性分析1981年2月至1998年4月连续施行的4000例肝移植资料（随访至2000年3月），并对移植时供，受体年龄，受体性别和诊断以及上份等因素进行比较；也统计了再移植率，再移植原因和死亡原因。结果：全组的总生存率为59％，统计18年生存率为48％；小儿，女性和1990年以后接受移植的病人生存情况产好。以FK506为基础的免疫抑制剂使因急，慢性排斥反应而施行的再移植率显著下降，手术一年后，移植肝脏丧失功能病人死亡的曲线相对趋于平稳，疾病复发，急性肿瘤和与年龄相关的并发症是移植物丧失功能的最主要因素。结论：随着年供的推移，病人和移植物的生存活情况获显著改善，由急性，慢性排斥反应所致的移植物失功已属十分罕见，与年龄相关和疾病相关的移植物失功，已构成肝移植患者长期生存的最大威胁。     

Short- and long-term results of liver transplantation according to age at transplant: a single-center experience of 351 children

Pediatric liver transplantation (PLT) has very good results at experienced transplant centers. However, there is still an ongoing discussion about inferior outcomes, especially in young infants. The aim of this retrospective study was to evaluate outcomes of infants compared to older recipients in a single center over 20 years. We conducted a retrospective study of children who received liver transplants at our center between 1991 and 2011. Only patients without other limiting organ involvement were included and compared according to age. The inclusion criteria were fulfilled by 351 patients (173 vs. 178). The most common indication in both groups was biliary atresia (82.1% vs. 49.4%). The 1-, 5-, and 10-year patient survivals were 93.8%/91.8%/91.1% and 93%/90.8%/90.1%, and the graft survivals were 90.4%/83.5%/79.6% and 89.4%/81.8%/77.5%, respectively. Complications such as postoperative bleeding, biliary complications, or perfusion impairment occurred more often in infants. Leading indications for retransplantation (vascular complications/primary nonfunction) and leading causes of death (sepsis/multiorgan failure) were the same in both groups. Significant predictors for patient loss were decade of transplantation, retransplantation, postoperative bleeding, and infections for infants. Predictors for graft loss were bowel perforation, arterial thrombosis, and age >12 months. Children can have excellent results, independent of age at PLT.     

Transplant Center Volume and Outcomes After Liver Retransplantation

Liver retransplantation surgery has a high rate of allograft failure due to patient comorbidities and technical demands of the procedure. Success of liver retransplantation could depend on surgeon experience and processes of care that relate to center volume. We performed a retrospective cohort study of adult liver retransplantation procedures performed from January 1, 1996 through December 31, 2005 using registry data from the Organ Procurement Transplantation Network. The primary outcome was 1-year allograft failure. Liver transplant centers were categorized as small, intermediate or high volume by dividing overall liver transplants into three tertiles of approximately equal size. Mean annual volume of overall liver transplants was <50 for low-volume centers, 50–88 for intermediate-volume centers and >88 for high-volume centers. The primary analysis consisted of 3977 liver retransplantation patients. The unadjusted risk of 1-year allograft failure was 37.8%. In multivariable logistic regression, the risk of 1-year allograft failure was not significantly different between low- (reference), intermediate- (OR 0.86, CI 0.72–1.03, p = 0.11) and high-volume centers (OR 0.88, CI 0.74–1.04, p = 0.14). Results were similar when the analysis was limited to retransplantation performed >160 days after initial transplantation. Center volume is an imprecise surrogate measure for 1-year outcomes after liver retransplantation.     

Long-term survival after retransplantation of the liver.

OBJECTIVE: The authors determined the long-term outcome of patients undergoing hepatic retransplantation at their institution. Donor, operative, and recipient factors impacting on outcome as well as parameters of patient resource utilization were examined. SUMMARY BACKGROUND DATA: Hepatic retransplantation provides the only available option for liver transplant recipients in whom an existing graft has failed. However, such patients are known to exhibit patient and graft survival after retransplantation that is inferior to that expected using the same organs in naiive recipients. The critical shortage of donor organs and resultant prolonged patient waiting periods before transplantation prompted the authors to evaluate the results of a liberal policy of retransplantation and to examine the factors contributing to the inferior outcome observed in retransplanted patients. METHODS: A total of 2053 liver transplants were performed at the UCLA Medical Center during a 13-year period from February 1, 1984, to October 1, 1996. A total of 356 retransplants were performed in 299 patients (retransplant rate = 17%). Multivariate regression analysis was performed to identify variables associated with survival. Additionally, a case-control comparison was performed between the last 150 retransplanted patients and 150 primarily transplanted patients who were matched for age and United Network of Organ Sharing (UNOS) status. Differences between these groups in donor, operative, and recipient variables were studied for their correlation with patient survival. Days of hospital and intensive care unit stay, and hospital charges incurred during the transplant admissions were compared for retransplanted patients and control patients. RESULTS: Survival of retransplanted patients at 1, 5, and 10 years was 62%, 47%, and 45%, respectively. This survival is significantly less than that seen in patients undergoing primary hepatic transplantation at the authors' center during the same period (83%, 74%, and 68%). A number of variables proved to have a significant impact on outcome including recipient age group, interval to retransplantation, total number of grafts, and recipient UNOS status. Recipient primary diagnosis, cause for retransplantation, and whether the patient was retransplanted before or after June 1, 1992, did not reach statistical significance as factors influencing survival. In the case-control comparison, the authors found that of the more than 25 variables studied, only preoperative ventilator status showed both a significant difference between control patients and retransplanted patients and also was a factor predictive of survival in retransplanted patients. Retransplant patients had significantly longer hospital and intensive care unit stays and accumulated total hospitalization charges more than 170% of those by control patients. CONCLUSIONS: Hepatic retransplantation, although life-saving in almost 50% of patients with a failing liver allograft, is costly and uses scarce donor organs inefficiently. The data presented define patient characteristics and preoperative variables that impact patient outcome and should assist in the rational application of retransplantation.     

Cardiac retransplantation in childhood: analysis of data from the United Network for Organ Sharing

OBJECTIVE: For children in whom graft failure develops after cardiac transplantation, retransplantation is often considered. Although some centers have reported equivalent results for retransplantation as for primary transplantation, this strategy remains controversial. We sought to examine outcomes after retransplantation in children and to identify risk factors for mortality. METHODS: United Network for Organ Sharing records of heart transplantation for subjects younger than 18 years from 1987 to 2004 were reviewed. Indications for retransplantation and patient characteristics were evaluated. Analysis was performed with proportional hazards regression, controlling for other potential risk factors. RESULTS: Among the 4227 pediatric heart transplants, there were 219 retransplants. The most common indication for retransplantation was coronary allograft vasculopathy (51%). The mean interval from initial heart transplant to retransplantation was 4.7 +/- 3.8 years. Forty-two retransplants (19%) were performed within 180 days of primary transplantation. Survivals at 1, 5, and 10 years after retransplantation were 79%, 53%, and 44%, respectively. In multivariate analysis, retransplantation was associated with significantly higher mortality than primary transplantation (odds ratio 1.67, 95% confidence interval 1.32-2.12, P < .001). Patients who underwent retransplantation within 180 days of primary transplantation had a significantly lower 1-year survival than did other retransplant recipients (53% vs 86%, respectively, P < .02). Subjects who required mechanical ventilation before retransplantation also had poorer survival (P < .03). CONCLUSION: Survival after cardiac retransplantation in children is inferior to that after primary transplantation. Although results are acceptable, the impact of retransplantation on the availability of donor hearts requires further consideration.     

Long-term outcomes of 600 living donor liver transplants for pediatric patients at a single center.

This report concerns the long-term outcome of living donor liver transplantation (LDLT) for pediatric patients at a single center. Between June 1990 and December 2003, a total of 600 LDLTs, including 568 primary transplantations and 32 retransplantations, were performed for pediatric patients, who were immunosuppressed with FK506 and low-dose corticosteroids. Patient survival at 1, 5, and 10 years were 84.6%, 82.4%, and 77.2%, respectively, and the corresponding findings for graft survivals were 84.1%, 80.9%, and 74.5%. Multivariate analysis demonstrated that fulminant hepatic failure (FHF), a graft vs. body weight (GBWR) ratio of <0.8, and ABO-incompatible transplants were independently associated with both patient and graft survival. The retransplantation rate was 6%, and 55 patients (9.7%) have been completely weaned off immunosuppressants. Long-term patient and graft survival after pediatric LDLT for a large cohort of children at our hospital were found to be as good as those for cadaveric liver transplantation, although this series includes 13% liver transplantations with ABO-incompatible donors, which are obviously inferior in patient and graft survival. To obtain better outcomes for patients with FHF and for patients with ABO-incompatible transplants, immunosuppressive therapy needs to be improved.     

Outcomes of Pediatric Kidney Transplantation in Recipients of a Previous Non‐Renal Solid Organ Transplant

Children who receive a non‐renal solid organ transplant may develop secondary renal failure requiring kidney transplantation. We investigated outcomes of 165 pediatric kidney transplant recipients who previously received a heart, lung, or liver transplant using data from 1988 to 2012 reported to the United Network for Organ Sharing. Patient and allograft survival were compared with 330 matched primary kidney transplant (PKT) recipients. Kidney transplantation after solid organ transplant (KASOT) recipients experienced similar allograft survival: 5‐ and 10‐year graft survival was 78% and 60% in KASOT recipients, compared to 80% and 61% in PKT recipients (p = 0.69). However, KASOT recipients demonstrated worse 10‐year patient survival (75% KASOT vs. 97% PKT, p < 0.001). Competing risks analysis indicated that KASOT recipients more often experienced graft loss due to patient death (p < 0.001), whereas allograft failure per se was more common in PKT recipients (p = 0.01). To study more recent outcomes, kidney transplants performed from 2006 to 2012 were separately investigated. Since 2006, KASOT and PKT recipients had similar 5‐year graft survival (82% KASOT vs. 83% PKT, p = 0.48), although 5‐year patient survival of KASOT recipients remained inferior (90% KASOT vs. 98% PKT, p < 0.001). We conclude that despite decreased patient survival, kidney allograft outcomes in pediatric KASOT recipients are comparable to those of PKT recipients.     

Liver Retransplantation in Children: A SPLIT Database Analysis of Outcome and Predictive Factors for Survival

To examine outcomes and identify prognostic factors affecting survival after pediatric liver transplantation, data from 246 children who underwent a second liver transplantation (rLT) between 1996 and 2004 were analyzed from the SPLIT registry, a multi-center database currently comprised of 45 North American pediatric liver transplant programs. The main causes for loss of primary graft necessitating rLT were primary nonfunction, vascular complications, chronic rejection and biliary complications. Three-month, 1- and 2-year patient survival rates were inferior after rLT (74%, 67% and 65%) compared with primary LT (92%, 88% and 85%, respectively). Multivariate analysis of pretransplant variables revealed donor age less than 1 year, use of a technical variant allograft and INR at time of rLT as independent predictive factors for survival after rLT. Survival of patients who underwent early rLT (ErLT, <30 days after LT) was poorer than those who received rLT >30 days after LT (late rLT, LrLT): 3-month, 1- and 2-year patient survival rates 66%, 59%, and 56% versus 80%, 74% and 61%, respectively, log-rank p = 0.0141. Liver retransplantation in children is associated with decreased survival compared with primary LT, particularly, in the clinical settings of those patients requiring ErLT.     

Liver retransplantation: a single-center outcome and financial analysis

Retransplantation of the liver (re-OLTx) accounts for approximately 10% of all liver transplants in the United States. The decision to offer a patient a second liver transplant has significant financial, ethical, and outcome implications. This large, single-center experience describes some outcome and financial data to consider when making this decision. One thousand three liver transplants were performed in 921 patients at our center. Patients were divided into adult and pediatric groups, and further by whether they received a single transplant or more than one. Overall survival, variation in survival by timing of re-OLTx, and survival in adults with hepatitis C were investigated, as were hospital charges and cost of re-OLTx. Adults, but not children, had a significant decrement in survival following a second transplant. Second transplants more than double the cost of the initial transplant, but there is a significantly higher cost associated with early retransplantation compared to the cost associated with late retransplantation (costs of first and second transplants included in both cases). This difference is due to a longer length of stay and associated cost in the ICU. Adult patients retransplanted early have the same overall survival compared to those done late. The sample size of the adult HCV re-OLTx population was too small to reach statistical significance despite their observed poorer outcome.     

Orthotopic liver transplantation in patients 60 years of age and older

Cyclosporine appears to have abrogated age as a contraindication to kidney transplantation in the elderly, although it is unclear whether this is true for other types of solid organ transplantation. We performed a retrospective analysis of liver transplant recipients who were 60 years of age and older (n = 23) versus recipients of primary transplants who were 18 to 59 years of age (n = 84). Indications in recipients over 60 included alcoholism (6), postnecrotic cirrhosis (6), cancer (4), primary biliary cirrhosis (3), sclerosing cholangitis (2), and one patient with polycystic liver disease. There were no important differences in the initial transplant hospitalization or the incidence of infection and rejection between the two groups. No patient in the over-60 population required retransplantation. Actuarial patient survival is 83% at 2 years for recipients 60 years of age and above compared to 76% patient survival in adult recipients who are under the age of 60. Liver transplant recipients over the age of 60 years have excellent patient and graft survival and the same postoperative morbidity as recipients who are under 60 years of age. Therefore, advanced age does not appear to be a contraindication to orthotopic liver transplantation.     

Indications for liver transplantation in the cyclosporine era

One hundred seventy orthotopic liver transplants were performed under conventional immunosuppression with azathioprine and steroids with 1- and 5-year survivals of 32.9 per cent and 20.0 per cent, respectively. Since the introduction of cyclosporine-prednisone therapy in March 1980, 313 primary orthotopic liver transplants have been performed. Actuarial survivals at 1 and 5 years have improved to 69.7 per cent and 62.8 per cent, respectively. Biliary atresia is now the most common indication for liver replacement. In adults, primary biliary cirrhosis and sclerosing cholangitis have become more common indications for transplantation, and alcoholic cirrhosis and primary liver malignancy as indications have declined. Early enthusiasm for liver transplantation in patients with hepatic cancer has been tempered by the finding that recurrence is both common and rapid. An increasing number of patients with inborn errors of metabolism originating in the liver are receiving transplants, including patients with Wilson's disease, tyrosinemia, alpha-1-antitrypsin deficiency, glycogen storage disease, familial hypercholesterolemia, and hemochromatosis. Survival in this group of patients has been excellent (74.4 per cent at 1 and 5 years). A hemophiliac who received a transplant for postnecrotic cirrhosis has survived and may have been cured of his hemophilia. About 20 per cent of patients require retransplantation for rejection, technical failure, or primary graft failure. Only four of the patients receiving retransplants under conventional immunosuppression survived beyond 6 months, and all died within 14 months of retransplantation. Sixty-eight patients have received retransplants under cyclosporine-prednisone. Thirty-one patients are surviving, all for at least 1 year. Six of the twelve patients requiring a third transplant are alive 2 to 3 years after the primary operation. An aggressive approach to retransplantation in the patient with a failed graft is justified.     

Split and whole liver transplantation outcomes: a comparative cohort study.

A specific split liver transplantation (SLT) program has been pursued in the North Italian Transplant program (NITp) since November 1997. After 5 yr, 1,449 liver transplants were performed in 7 transplant centers, using 1,304 cadaveric donors. Whole liver transplantation (WLT) and SLT were performed in 1,126 and 323 cases, respectively. SLTs were performed in situ as 147 left lateral segments (LLS), 154 right trisegment liver (RTL) grafts, and 22 modified split livers (MSL), used for couples of adult recipients. After a median posttransplant follow-up of 22 months, SLTs achieved a 3-yr patient and graft survival not significantly different from the entire series of transplants (79.4 and 72.2% vs. 80.6 and 74.9%, respectively). Recipients receiving a WLT or a LLS showed significantly better outcomes than patients receiving RTL and MSL (P < 0.03 for patients and P < 0.04 for graft survival). At the multivariate analysis, donor age of >60 yr, RTL transplant, <50 annual transplants volume, urgent transplantation (United Network for Organ Sharing (UNOS) status I and IIA), ischemia time of >7 hours, and retransplantation were factors independently related to graft failure and to significantly worst patient survival. Right grafts procured from RTL and either split procured as MSL had a similar outcome of marginal whole livers. In conclusion, in 5 yr, the increased number of pediatric transplants due to split liver donation reduced to 3% the in-list children mortality, and a decrease in the adult patient dropout rate from 27.2 to 16.2% was observed. Such results justify a more widespread adoption of SLT protocols, organizational difficulties not being a limit for the application of such technique.     

再次肝移植--挽救肝移植失败受体生命唯一的手段(附774例报告)

目的 评估肝移植，尤其是再次肝移植的长期随访结果及影响结果的因素。方法 对1981年2月至1998年4月期间进行的、存活时间大于2年的4000例肝移植进行随访，其中再次肝移植774例。根据首次肝移植的时间，分为A、B、C三期。结果 774例（19．4％）接受第2次肝移植，148例（3．7％）接受第3次肝移植，20例（0．5％）接受第4次肝移植，5例（0．13％）接受第5次及5次以上肝移植。第1次再移植原因主要为移植肝原发性无功能、肝动脉栓塞和排斥反应。C期再次肝移植率（13．4％）明显低于A期（33．4％）和B期（23．7％），P＝0．001。结论 掌握适当的再移植指征、再次手术时机、受体的选择和手术技巧，再次肝移植的长期生存率明显改善。     

Incidence and outcome of Levitronix CentriMag support as rescue therapy for early cardiac allograft failure: a United Kingdom national study

Objective: Primary graft failure is the most common cause of mortality early after heart transplantation. The availability of relatively low-cost short-term mechanical support devices has altered the management of primary graft failure but there are few data on clinical outcome. Here, we describe the UK experience with Levitronix CentriMag support following heart transplantation across multiple centres. Methods: Data for all adult heart transplants and all CentriMag devices used within 30 days of heart transplantation in the UK between November 2003 and July 2008 were collected. Transplant characteristics were compared for those who did and did not receive CentriMag support, and device outcomes and survival rates were summarised. Results: A total of 572 heart transplants were performed in this period. As many as 38 patients (6.6%) were implanted with CentriMag devices for primary graft failure. Four patients received extracorporeal membrane oxygenation concurrently and were excluded from further analysis. There were no significant differences in transplant characteristics between the patients who received CentriMag support and those who did not. Twelve patients were explanted; nine survived but three died shortly afterwards. Five underwent acute retransplantation; two survived and three died. Seventeen patients died on support. The 30-day and 1-year survival rates were 50% (95% confidence interval (CI) 32–65%) and 32% (95% CI 18–48%), respectively. Patients who previously had a bridge-to-transplant ventricular assist device (VAD) had significantly better survival than those who did not (1-year survival 71% vs 22%, p = 0.029). Conclusions: Primary graft failure remains an important early complication of heart transplantation. Levitronix CentriMag support led to the salvage of 32% of patients with severe allograft failure.     

Retransplantation for hepatic allograft failure: Prognostic modeling and ethical considerations

Retransplantation already accounts for 10% of all liver transplants performed, and this percentage is likely to increase as patients live long enough to develop graft failure from recurrent disease. Overall, retransplantation is associated with significantly diminished survival and increased costs. This review summarizes the current causes of graft failure after primary liver transplant, prognostic models that can identify the subset of patients for retransplantation with outcomes comparable to primary transplantation, and ethical considerations in this setting, i.e., outcomes-based versus urgency-based approaches. (Liver Transpl 2002;8:313-322.)