Evolving trends in liver transplantation: listing and liver donor allocation.

The success of liver transplantation in the past three decades as a life-saving procedure for patients with end-stage liver disease has led to the ever-increasing disparity between the demands for liver transplantation and the supply of donor liver organs. Donor allocation and distribution remains a challenge and a moral issue as to how these organs can be equitably distributed. This article reviews the evolution of the liver allocation policy and discusses in detail the challenges clinicians face today in this area of medicine.

Liver transplantation for hepatocellular cancer: the impact of the MELD allocation policy.

Recent reports suggest that selected patients undergoing liver transplantation for stage 1-2 hepatocellular cancer (HCC) have an excellent long-term survival and a low incidence of recurrence. In the past, over 45% of HCC patients on the United Network for Organ Sharing/Organ Procurement Transplantation Network waiting list did not receive a donor organ for up to 2 years. This resulted in not only a high mortality rate but a high rate of being removed from the waiting list because of progression of HCC to advanced stages. The introduction of the Model for End-Stage Liver Disease (MELD) allocation policy has had a positive effect on HCC liver transplant candidates with the number of patients transplanted for HCC significantly increasing over the past several years. In addition, waiting time for HCC patients to receive a deceased donor has decreased significantly and the number of patients dropping out from the waiting list because of advanced stage disease has also decreased. An early assessment of the MELD allocation policy suggests that posttransplant survival for HCC patients comparing pre-MELD to post-MELD eras is similar. Using the data we have collected on the MELD allocation policy, we have already made modifications to the MELD allocation policy for HCC patients. It is hoped that through continued data collection and assessment, a consensus can be reached to further optimize the use of deceased donors in HCC recipients.

Summary report of a national conference: Evolving concepts in liver allocation in the MELD and PELD era. December 8, 2003, Washington, DC, USA.

A national conference was held to review and assess data gathered since implementation of MELD and PELD and determine future directions. The objectives of the conference were to review the current system of liver allocation with a critical analysis of its strengths and weaknesses. Conference participants used an evidence-based approach to consider whether predicted outcome after transplantation should influence allocation, to discuss the concept of minimal listing score, to revisit current and potential expansion of exception criteria, and to determine whether specific scores should be used for automatic removal of patients on the waiting list. After review of data from the first 18 months since implementation, association and society leaders, and surgeons and hepatologists with wide regional representation were invited to participate in small group discussions focusing on each of the main objectives. At the completion of the meeting, there was agreement that MELD has had a successful initial implementation, meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, and that it has proven to be a powerful tool for auditing the liver allocation system. It was also agreed that the data regarding the accuracy of PELD as a predictor of pretransplant mortality were less conclusive and that PELD should be considered in isolation. Recommendations for the transplant community, based on the analysis of the MELD data, were discussed and are presented in the summary document.

MELD/PELD and the allocation of deceased donor livers for status 1 recipients with acute fulminant hepatic failure, primary nonfunction, hepatic artery thrombosis, and acute Wilson's disease.

1. Historical perspective of donor allocation to patients with fulminant hepatic failure (FHF). 2. Predicting prognosis in patients with FHF using the London and Clichy criteria. 3. Model for end-stage liver disease (MELD) is a predictor of mortality in patients with FHF. 4. Outcomes of adults listed as Status 1 in the United States. 5. Outcomes of pediatric candidates listed as Status 1 in the United States. 6. Proposed redefinition for Status 1 in adult and pediatric candidates.

Improving liver allocation: MELD and PELD.

On February 27, 2002, the liver allocation system changed from a status-based algorithm to one using a continuous MELD/PELD severity score to prioritize patients on the waiting list. Using data from the Scientific Registry of Transplant Recipients, we examine and discuss several aspects of the new allocation, including the development and evolution of MELD and PELD, the relationship between the two scoring systems, and the resulting effect on access to transplantation and waiting list mortality. Additional considerations, such as regional differences in MELD/PELD at transplantation and the predictive effects of rapidly changing MELD/PELD, are also addressed. Death or removal from the waiting list for being too sick for a transplant has decreased in the MELD/PELD era for both children and adults. Children younger than 2 years, however, still have a considerably higher rate of death on the waiting list than adults. A limited definition of ECD livers suggests that they are used more frequently for patients with lower MELD scores.

Results of the first year of the new liver allocation plan.

Liver allocation policy in the U.S. was recently changed to a continuous disease severity scale with minimal weight given to time waiting in an effort to better prioritize deceased donor liver transplant candidates. We compared rates of waiting list registrations, removals, transplants, and deaths during the year prior to implementation of the new liver allocation policy (2/27/01-2/26/02, Era 1) with the first year's experience (2/27/02-2/26/03, Era 2) under this new policy. Rates were adjusted for 1,000 patient years on the waiting list and compared using z-tests. A 1-sided test was used to compare death rates; 2-sided tests were used to compare transplant rates. Overall and subgroup analyses were performed for demographic, geographic, and medical strata. In Era 2, we observed a 12% reduction in new liver transplant waiting list registrations, with the largest reductions seen in new registrants with low MELD/PELD scores. In Era 2, there was a 3.5% reduction in waiting list death rate (P =.076) and a 10.2% increase in cadaveric transplants (P <.001). The reduction in waiting list mortality and increase in transplantation rates were evenly distributed across all demographic and medical strata, with some variation across geographic variables. Early patient and graft survival after deceased donor liver transplantation remains unchanged. In conclusion, by eliminating the categorical waiting list prioritization system that emphasized time waiting, the new system has been associated with reduced registrations and improved transplantation rates without increased mortality rates for individual groups of waiting candidates or changes in early transplant survival rates.

Liver transplantation for hepatocellular carcinoma: the MELD impact.

The new allocation policy of the United Network of Organ Sharing (UNOS) based on the model for end-stage liver disease (MELD) gives candidates with stage T1 or stage T2 hepatocellular carcinoma (HCC) a priority MELD score beyond their degree of hepatic decompensation. The aim of this study was to determine the impact of the new allocation policy on HCC candidates before and after the institution of MELD. The UNOS database was reviewed for all HCC candidates listed between July 1999 and July 2002. The candidates were grouped by two time periods, based on the date of implementation of new allocation policy of February 27, 2002. Pre-MELD candidates were listed for deceased donor liver transplantation (DDLT) before February 27,2002, and post-MELD candidates were listed after February 27, 2002. Candidates were compared by incidence of DDLT, time to DDLT, and dropout rate from the waiting list because of clinical deterioration or death, and survival while waiting and after DDLT. Incidence rates calculated for pre-MELD and post-MELD periods were expressed in person years. During the study, 2,074 HCC candidates were listed for DDLT in the UNOS database. The DDLT incidence rate was 0.439 transplant/person years pre-MELD and 1.454 transplant/person years post-MELD (P < 0.001). The time to DDLT was 2.28 years pre-MELD and 0.69 years post-MELD (P < 0.001). The 5-month dropout rate was 16.5% pre-MELD and 8.5% post-MELD (P < 0.001). The 5-month waiting-list survival was 90.3% pre-MELD and 95.7% post-MELD (P < 0.001). The 5-month survival after DDLT was similar for both time periods. The new allocation policy has led to an increased incidence rate of DDLT in HCC candidates. Furthermore, the 5-month dropout rate has decreased significantly. In addition, 5-month survival while waiting has increased in the post-MELD period. Thus, the new MELD-based allocation policy has benefited HCC candidates.

Effect of minimal listing criteria on waiting list registration for liver transplantation: a process-outcome analysis.

OBJECTIVE: To determine the level of association between minimal listing criteria (MLC) recognition and outcomes associated with waiting list registration for liver transplantation (LT). PATIENTS AND METHODS: A total of 147 patients and 201 patients were identified as first-time referrals for LT evaluation between January 1, 1997, and November 30, 1997 (cohort A), and December 1,1997, and December 31, 1998 (cohort B), respectively. Relevant demographic and clinical information was abstracted from medical records. Minimal listing criteria were defined as a Child-Turcotte-Pugh (CTP) score of 7 or higher. RESULTS: Patient age, sex, hepatic disease etiology, and mean CTP scores were similar between cohorts A and B. However, the proportion of registered patients in cohort B with CTP scores of 7 or higher increased significantly after formal MLC recognition (96% vs 82% for cohort A; P=.001). In cohort A, waiting list registration was based on patient age, male sex, nonalcohol-related hepatic disease, and a CTP score of 7 or higher in the absence of formal MLC. The rate of first-time patient referral was also increased in cohort B vs cohort A after formal MLC recognition (80% vs 69%, respectively; P=.002) despite similar clinical characteristics. Although the number of patients with a CTP score of 10 or higher was greater in cohort B vs cohort A, the proportion of patients with advanced end-stage liver disease was similar (29% vs 26%, respectively; P=.72). CONCLUSION: The explicit recognition of MLC was strongly associated with improvements in appropriate waiting list registration for LT.

The new liver allocation system: moving toward evidence-based transplantation policy.

In 1999, the Institute of Medicine suggested that instituting a continuous disease severity score that de-emphasizes waiting time could improve the allocation of cadaveric livers for transplantation. This report describes the development and initial implementation of this new plan. The goal was to develop a continuous disease severity scale that uses objective, readily available variables to predict mortality risk in patients with end-stage liver disease and reduce the emphasis on waiting time. Mechanisms were also developed for inclusion of good transplant candidates who do not have high risk of death but for whom transplantation may be urgent. The Model for End-Stage Liver Disease (MELD) and Pediatric End-Stage Liver Disease (PELD) scores were selected as the basis for the new allocation policy because of their high degree of accuracy for predicting death in patients having a variety of liver disease etiologies and across a broad spectrum of liver disease severity. Except for the most urgent patients, all patients will be ranked continuously under the new policy by their MELD/PELD score. Waiting time is used only to prioritize patients with identical MELD/PELD scores. Patients who are not well served by the MELD/PELD scores can be prioritized through a regionalized peer review system. This new liver allocation plan is based on more objective, verifiable measures of disease severity with minimal emphasis on waiting time. Application of such risk models provides an evidenced-based approach on which to base further refinements and improve the model.