Richard B. Freeman

Skin cancer is a well-recognized long-term complication of transplantation and immunosuppression. Although risk factors for the development of skin cancer in the general population are well defined, risk factors for the development of these lesions have not been identified clearly in the liver transplant population. We surveyed 151 liver transplant (LTx) recipients for risk factors associated with cutaneous malignancies in the general population. Variables included were: demographics, primary liver disease, severity of disease at LTx, immunosuppression history, complexion, hair color, eye color, tanning profile, number of moles, occupational history, sun exposure history, sunburn history, family history of skin cancer, and any history of removed skin lesions. All skin cancers were confirmed histologically. There were 86 documented skin cancers in 34 patients: 56 squamous cell, 23 basal cell and 7 melanomas. Median follow-up was 1490 days. In a univariate analysis, age, male gender, red hair, brown eyes, primary sclerosing cholangitis (PSC), primary biliary cirrhosis (protective), cyclosporine, number of second degree sunburns, and frequent lifetime sun exposure were associated with the development of new skin cancers. In a multivariate model, age, male gender, red hair, brown eyes, PSC, and cyclosporine remain the strongest predictors. The incidence of skin cancer after liver transplantation is underestimated. In particular, there is a higher incidence of squamous cell carcinoma compared with the general population. Recipients with identified risk factors may be candidates for prophylactic treatment and should be followed more intensively after liver transplantation.

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.

For several years, the Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) Liver and Intestinal Transplantation Committee has been examining effects of changes and proposed changes to the liver allocation system. The Institute of Medicine recently recommended that the size of liver distribution units be increased to improve the organ distribution system. Methods to achieve this and the potential impact on patients and transplant centers of such a change are evaluated in this study. In hypothetical scenarios, we combined geographically contiguous organ procurement organizations (OPOs) in seven different configurations to increase the size of liver distribution units to cover populations greater than 9 million persons. Using the UNOS Liver Allocation Model (ULAM), we examined the effect of 17 different organ allocation sequences in these proposed realignments and compared them with those predicted by ULAM for the current liver distribution system by using the following primary outcome variables: number of primary liver transplantations performed, total number of deaths, and total number of life-years saved. Every proposed new liver distribution unit plan resulted in fewer primary transplantations. Many policies increased the total number of deaths and reduced total life-years saved compared with the current system. Most of the proposed plans reduced interregional variation compared with the current plan, but no one plan consistently reduced variation for all outcome variables, and all reductions in variations were relatively small. All new liver distribution unit plans led to significant shifts in the number of transplantations performed in individual OPOs compared with the current system. The ULAM predicts that changing liver distribution units to larger geographic areas has little positive impact on overall results of liver transplantation in the United States compared with the current plan. Enlarging liver distribution units likely will result in significant shifts in organs across current OPO boundaries, which will have a significant impact on the activity of many transplant centers.

Liver allocation remains problematic because current policy prioritizes status 2B or 3 patients by waiting time rather than medical urgency. On February 21, 2000, we implemented a variance to the United Network for Organ Sharing liver allocation policy that redefined status 2A by much more rigid, definable criteria and prioritized status 2B patients by using a continuous medical urgency score based on the Child-Turcotte-Pugh score and other medical conditions. In this system, waiting time is used only to differentiate status 2B candidates with equal medical urgency scores. Comparing the 6-month period (period 1; n = 67) before implementation of this system to the 6-month period after implementation (period 2; n = 75), there was a significant reduction in the number of transplantations performed for patients listed as status 2A (46.3% to 14.7%; P = .002) and an increase in the number of patients listed as status 2B who received transplants (44.8% to 70.7%; P = .10). Most dramatically, there was a 37.1% reduction in overall deaths on the waiting list from 94 deaths in period 1 to 62 deaths in period 2 (P = .005), with the most significant reduction for patients removed from this list at status 2B (52 v 18 patients; P = .04). There were 3 postoperative deaths in each period, with only 1 graft lost in period 2. Status 2B patients with the greatest degree of medical urgency received transplants without multiple peer reviews requesting elevation to 2A status. We conclude that a continuous medical urgency score system allocates donor livers much more fairly to those in medical need and reduces waiting list mortality without sacrificing efficacy.

Factors associated with the risk for mortality once placed on the liver transplant waiting list and how this risk relates to center-specific waiting time and transplant activity have not been adequately evaluated. We performed this study to determine the association between center-specific waiting time and waiting list mortality among liver transplant candidates stratified by medical urgency at the time of registration. A Cox proportional hazards model was used to calculate 2-year mortality risk for a cohort of 16,414 registrants added to the United Network for Organ Sharing liver transplant waiting list between January 1, 1997, and December 31, 1997. After controlling for confounding variables, we calculated the mortality risk for centers, organ procurement organizations (OPOs), and states. The relation between center-specific waiting list mortality risk and median waiting time or transplant activity was determined by linear regression. In multivariate analyses, higher initial medical urgency status (relative risk [RR] = 12.8; P < .001), increasing age (P < .001), black ethnicity (RR = 1.29; P < .001), history of previous transplant (RR = 1.2; P = .009), certain liver diagnoses, and smaller center size (RR = 1.39; P = .008) were associated with significantly increased waiting list mortality. Candidates with blood type A (RR = 0.87; P < .001) and those with cholestatic cirrhosis as the primary diagnosis (RR = 0.73; P < 0.001) had a reduced risk for dying. There were significant variations in 2-year waiting list mortality risk among centers, OPOs, and states. However, when stratified by medical urgency status at waiting list entry, center-specific waiting time and transplantation rates accounted for almost none of the center-specific waiting list mortality. Although there are variations in waiting list mortality risk among centers, OPOs, and states, there is very little relation between center-specific waiting list mortality and center-specific median waiting time or center-specific transplantation rates when stratified by medical urgency. Waiting time and center transplant rates should not influence liver allocation policy.

John P. A. Ioannidis, David R. Snydman, Richard J. Rohrer, Richard B. Freeman, Craig E. Haug; Aspergillus fumigatus Infection of a Biloma, Clinical Infectious D