Differences in Access to Liver Transplantation: Disease Severity, Waiting Time, and Transplantation Center Volume

Context Under the current system of organ allocation, sicker patients with liver disease get higher priority for liver transplants. Contribution Using national data, the investigators found that patients waiting for transplants at higher-volume transplantation centers received transplants at lower disease severity scores and have shorter waiting times than patients waiting for transplants at lower-volume transplantation centers. Caution The study could not determine whether the observed differences led to differences in clinical outcomes. Implications Although the current liver allocation system is need-based, transplantation priority still differs by transplantation center. Patients listed at higher-volume centers seem to receive transplants at lower disease severity scores and with shorter delays. The Editors In the late 1990s, major inequalities in the distribution of livers from deceased donors for transplantation became apparent. Organ allocation was based on time accrued on the recipient waiting list, geography, and several subjective measures of medical urgency. This led to discrepancies in waiting times across geographic regions and suggested that patients' chances of receiving a transplant were affected by where they lived (1). Hence, the U.S. Department of Health and Human Services issued the final rule regulation in 1998, stating that the allocation of livers from deceased donors should be based primarily on medical urgency and less emphasis should be placed on keeping organs in local procurement areas (2). The final rule resulted in initial strong opposition within the transplantation community because of fears that smaller transplantation programs would be forced to close and that organ donation could decrease if potential donors opposed sending organs to other regions. The Institute of Medicine was asked to review the impact of the final rule and recommended that service areas for organ procurement organizations be increased to a population base of 9 million people and that disease severity should be based on an objective point system to deemphasize waiting time (3). Although the size of organ procurement organizations did not change, the Model for End-Stage Liver Disease (MELD) score was adapted in February 2002 and has since been used in the United States as the basis for allocating adult livers from deceased donors to patients with chronic liver disease. The MELD score, which is based on serum creatinine level, bilirubin level, and international normalized ratio (INR), estimates severity of illness from the following equation: MELD estimate=6.43+9.57*log(creatinine)+ 3.78*log(bilirubin)+11.2*log(INR). The result is then rounded to the nearest integer from 6 to 40 (inclusive), with sicker patients having a higher score. (In practice, MELD scores can be routinely computed by using an online calculator available through the United Network for Organ Sharing [UNOS] Web site: www.unos.org/resources/meldPeldCalculator.asp.) The MELD score accurately predicts 3-month mortality rates among patients with chronic liver disease who are on the waiting list, and the area under the receiver-operating characteristic curve is improved compared with that of the ChildTurcottePugh score (4). Initial resistance to MELD because of concerns that smaller transplantation programs would close seems unwarranted: Between 2001 (the year before MELD) and 2005, the number of centers conducting adult liver transplantations increased from 101 to 107, and more than half of these centers perform fewer than 50 transplantations per year (5). Under the MELD system, which provides a more formalized method for distributing organs, sicker patients with higher MELD scores should have shorter waiting times. Demographic variables (such as sex, race, and age) and center variables (particularly transplantation center volume) should not affect the timing of transplantation. We aimed to determine whether the severity of liver disease differed among liver transplant recipients, as assessed by the MELD score at time of transplantation and according to the transplantation center volume, and whether the waiting times for transplants differed among recipients, according to the transplantation center volume, even in patients with equal severity of disease. Methods Patients We received a deidentified data file from the UNOS on 22630 recipients of livers from deceased donors since the implementation of the MELD priority system (based on Organ Procurement and Transplantation Network data as of 7 July 2006). Children (age <18 years) were not included in the data file, because organ allocation in children is determined by using a different assessment of priority status. We eliminated 1588 recipients (7.0%) who had acute liver failure because they are placed in a separate category on the waiting list and are not assigned a MELD score. We also excluded 737 recipients (3.3%) who had received a previous transplant, 78 recipients (0.3%) whose status at the time of transplantation was assigned with the previous priority system, 133 recipients (0.6%) with missing information on transplantation center volume, and 19 recipients (0.08%) with missing information on waiting time, which left us with 20075 recipients who received their primary liver transplant under the MELD system between 27 February 2002 and 30 April 2006 (based on UNOS data as of 1 June 2006). Outcome Measures Our main outcome was the number of days on the waiting list, defined as the time from listing to transplantation. The file also contained information on recipients' age, sex, race or ethnicity (white, black, Hispanic, Asian, or other or unknown), blood type, primary diagnosis, and MELD score at time of transplantation and age of donors. We did not know the name of the transplantation center, but we did know the year of transplantation, center location (11 geographic regions defined by UNOS), and number of procedures performed by the center in 2005. On the basis of previous work (6), we aggregated the UNOS primary diagnosis variable for chronic conditions (66 possibilities) into 9 major liver disease categories: hepatitis C infection, autoimmune disorder, alcoholic liver disease, hepatocellular carcinoma, primary sclerosing cholangitis, primary biliary cirrhosis, hepatitis B infection, metabolic disease, and other chronic diseases. Our primary covariate of interest was transplantation center volume (low, medium, or high), which was based on the number of procedures performed by the center in 2005. We defined low volume as fewer than 50 procedures, medium volume as 50 to 99 procedures, and high volume as 100 or more procedures (7), according to previous evidence that these volumes are important predictors of transplantation success. The University of Pittsburgh Institutional Review Board, Pittsburgh, Pennsylvania, approved the study. Statistical Analysis Initially, we examined the characteristics of our sample, both overall and by category (low-, medium-, high-volume center). We tested for differences in the distribution across transplantation centers by using analysis of variance for the means of continuous variables (recipient age, recipient sex, and donor age), the nonparametric K-sample test for the medians of continuous variables (days on the waiting list and MELD score), the JonckheereTerpstra test for ordered alternatives (priority at time of transplantation, based on MELD score), and the KruskalWallis test for categorical variables (all other variables). We then estimated the number of days on the waiting list by using negative binomial regression to account for the skewness in waiting time. We first calculated unadjusted waiting times, accounting for clustering by center-specific variables (geographic region and number of procedures performed in 2005). In the multivariable (adjusted) model, we adjusted for recipient demographic characteristics (age, sex, and race or ethnicity) and clinical characteristics that influence waiting time, namely recipient blood type, category of liver disease, and MELD score at time of transplantation. We also controlled for year of transplantation and transplantation center region, both of which have been shown to be associated with liver transplant waiting times (1, 5). Finally, we included the main covariate of interest, transplantation center volume (low, medium, or high), as well as an interaction term between volume and MELD score. Again, we accounted for clusters by using center-specific variables. We used the expected values from both models to compare the unadjusted and adjusted waiting times stratified by MELD score and transplantation center volume. We used 1000 repetitive bootstrapped samples of the original data set to calculate 95% CIs for these estimated differences. Because our classification for low-volume centers was subjective, we conducted a sensitivity analysis by repeating the analysis with a more stringent definition of low volume (<20 transplantations in 2005). Researchers have reported that programs conducting fewer than 20 transplantations per year have poorer 1-year survival rates (8), possibly because of inadequate technical expertise (911) or differences in the case mix of recipients. In our sensitivity analysis, we again compared unadjusted and adjusted waiting times by MELD score and transplantation center volume. We used SAS, version 8.2 (SAS Institute Inc., Cary, North Carolina), and STATA, version 8 (Stata Corp., College Station, Texas), for all analyses. Role of the Funding Source We did not receive funding for this study. There is no conflict of interest with any company, institution, or funding agency. Results Table 1 describes the characteristics of the 20075 patients in our sample who have received liver transplants from deceased donors since the advent of the MELD scoring system. In 2005, 63 centers performed fewer than 50 transplantations, 27 centers performed 50 to 99 transplantations, and 17 centers performed 1