The New Liver Allocation System: Moving Toward Evidence-Based Transplantation Policy

Transcription

1 SPECIAL ARTICLE The New Liver Allocation System: Moving Toward Evidence-Based Transplantation Policy Ricbard B. Freeman, Jr, * Russell H. Wiesner, 'Ann Harper," Sue V: McDiarmid,s Jack Lake? Erick Edwards,' Robert Merion, W Robert WO&," ** Jeremiab Turcotte, ' and Lewis Teperman"for the UNOS/OPTN Liver Disease Severity Score, UNOS/OPTN Liver and Intestine, and UNOS/OPTN Pediatric Transplantation Committees In 1999, the Institute of Medicine suggested that institut- 6 weeks duration or patients who have received a liver ing a continuous disease severity score that de-emphasizes transplanthat has failed within 1 week. Pediatric waiting time could improve the allocation of cadaveric patients with chronic severe liver disease requiring livers for transplantation. This report describes the development and initial implementation of this new plan. The intensive care may also qualify for the status 1 designagoal was to develop a continuous disease severity scale that tion. Status 2A patients were adult patients having a uses objective, readily available variables to predict mor- CTP score 2 10 and having a life-threatening complitality risk in patients with end-stage liver disease and cation of their liver disease. Patients classified as status 1 reduce the emphasis on waiting time. Mechanisms were or 2A were prioritized by their time waiting (TW) at also developed for inclusion of good transplant candidates who do not have high risk of death but for whom transthese status definitions regardless of how long they may plantation may be urgent. The Model for End-Stage Liver have been on the list at less urgent designations. Patients Disease (MELD) and Pediatric End-Stage Liver Disease having CTP scores of 210, but without severe compli- (PELD) scores were selected as the basis for the new allo- cations of portal hypertension, were classified as 2B, cation policy because of their high degree of accuracy for and all other active patients meeting the minimum listpredicting death in patients having a variety of liver disease etiologies and across a broad spectrum of liver disease ing requirements were classified as status 3. Patients severity. Except for the most urgent patients, all patients meeting 2B or 3 status definitions were prioritized will be ranked continuously under the new policy by their within their groups by the total TW on the list. Patients MELD/PELD score. Waiting time is used only to priori- meeting the 2B definition comprised an extremely hettize patients with identical MELD/PELD scores. Patients erogeneous group with some patients deteriorating very who are not well served by the MELD/PELD scores can be slowly and others declining very rapidly although they prioritized through a regionalized peer review system. This new liver allocation plan is based on more objective, may not have been on the waiting list very long. As the verifiable measures of disease severity with minimal waiting list has grown in size, the number of patients emphasis on waiting time. Application of such risk models waiting in each status category grew considerably, addprovides an evidenced-based approach on which to base ing more importance to TW for determination of rank further refinements and improve the model. (Liver order on the waiting list. Also, as care of patients with Transpl2002;8: ) I n 2000, the Department of Health and Human Ser- vices (DHHS) adopted the Final Rule,' establishing that the primary guideline for allocation of cadaver livers for transplantation should be based on medical urgency. Over the years liver allocation policy has evolved from prioritizing liver transplant candidates based on their physical location (home, hospital, intensive care unit) to medical-based criteria (Child Turcotte Pugh [CTP] score)2 consistent with these guidelines. Historically, these medical urgency designations, or statuses, have remained categorical in nature with status 1, 2A, 2B, and 3 representing the most recent groupings. Status 1 patients are given the highest priority and are defined by the presence of acute liver failure of less than From the *Department of Surgey, Tufts-New England Medical Center/Tufts University School of Medicine, Boston, M; the?department of Medicine, Mayo Clinic, Rochester, MN; the $United Network jor Organ Sharing, Richmond, VA; the $Department ofpediatrics, University of California at Los Angeles, Los Angeles, CA; the IlDepartment of Medicine, University ofminnesota, Minneapolis, MN; the Departments of YSurgey and **Biostatistics, University OfMichigan, Ann Arbor, MI; the #Scientific Registry of Transplant Recipients, Ann Arbor, MI; and the f?department of Surgey, New fir& Universig, New York, NI: Address reprint requests to Richard B. Freeman, Jr, MD, Division of Transplant Surge y, New England Medical Center, Box 40, 750 Washington St, Boston, MA 021 l l. Telephone: ; FM: ; $-eeman@lifespan.org Copyright O 2002 by the American Association for the Study of Liver Diseases /02/ $35.00/0 doi: I ~lts Liver Transplantation, Vol8, No 9 (September), 2002: pp

2 852 Freeman et al end-stage liverdisease (ESLD) has improved, it has become apparent that the CTP scoredoes not adequately segregate patients with progressively abnormal laboratory test results. For example, the CTP score does not distinguish patients with serum bilirubin values of 3.5 mg/dl from those with serum bilirubin values of 10 mg/dl or 20 mg/dl or 40 mg/dl. The CTP score also includes subjective clinical measures, encephalopathy and ascites, which are subject to clinical interpretation and are much less objective. Furthermore, the CTP score had never been prospectively validated as a measure of disease severity or estimate of mortality risk in patients waiting on the liver transplant list. Faced with these deficiencies and the Institute of Medicine s (IOM) recommendation that a continuous disease severity score that de-emphasizes waiting time might be a more appropriate method of prioritizing liver transplant candidates,3 the United Network for Organ Sharing (UNOS; UNOS administers the national Organ Procurement and Transplantation Network [OPTN] under Federal Contract as stipulated by the National Organ Transplant Act). The OPTN Liver and Intestine Committee formed a subcommittee, the Liver Disease Severity Score (LDSS) Committee, to develop and assess a model that would more accurately estimate survival for patients on the waiting list. During the development of this new plan, it became readily apparent that this should be a fluid, constantly changing system whereby new data and experience are constantly reanalyzed and incorporated into the system where appropriate. This report outlines this effort and summarizes the new allocation policy (full details of this new policy can be found at under Policies, Policy number 3.6 Allocation of Livers). (status 1) was effective and reasonable at this time. The goal was to develop a new system of allocation for patients with chronic liver disease who do not meet the current status 1 definition. The UNOS/OPTN LDSS Committee s initial efforts were directed at identifying important predictors of mortality in patients with chronic liver disease to develop a continuous disease severity scale. Subjective clinical variables that can be difficult to verify, invasive tests, or variables with discriminatory implications such as age, gender, or race were avoided. The Model for End-Stage Liver Disease (MELD) was identified as potentially meeting these requirements. Pre- Table 1. MELD and PELD Score Equations MELD score Malinchoc et a14 R = X Log,(creatinine mg/dl) X LogJbilirubin mg/dl) X Log(1NR) X (disease etiology*) MELD score New Policy R = (0.957 X LogJcreatinine mg/dl] X Log[total bilirubin mg/dl] X Log,[INR] ) X 10 PELD score R = (0.463 [age?] X Log,[albumin g/dl] X LogJtotal bilirubin mg/dl] X Lo&[INR] [growth failure$]) X 10 NOTE. MELD score equations as reported by Malinchoc et a14 and as incorporated in the new liver allocation policy. The disease etiology variable included in the Malinchoc et a14 equation has been omitted but the constant is maintained (see text). PELD score includes bilirubin, albumin, and INR continuous variables and dichotomous variablesforage and growth failure. * 1 for noncholestatic disease, 0 for cholestatic disease.?<l yearofage + 1, 21 yearofage = 0. $>2 standard deviations below the mean for age = 1, 52 standard deviations below the median for age = 0. Intrahepatic Portocaval Shunt (TIPS) procedure^.^ This score incorporates laboratory values for serum creatinine, bilirubin, and International Normalized Ratio (INR) in a mathematical equation to derive a probability of survival (Table 1). In cooperation with the UNOS/OPTN Pediatric Transplantation Committee, we recognized that pediatric patients with ESLD might not be well served by the MELD model because it was derived from cohorts consisting of adults only and because serum creatinine has never found be to a predictor of mortality in either univariate or multivariate analyses of pediatric liver disease.5 Thus, the Pediatric End-Stage Liver Disease (PELD) severity score was developed using the Studies of Methods Pediatric Liver Transplantation (SPLIT) database.6 This scor- The general consensus among transplantation professionals, ing system incorporates dichotomous variables for age (51 and confirmed in the recent report by the IOM,3 was that the year of age U > 1 year of age) and growth failure (<2 standard current system for prioritizing patients with acute liver failure deviations U 22 standard deviations from the median for age) and laboratory values of serum bilirubin, albumin, and INR (Table 1). A preliminary proposal to modify liver allocation policy to prioritize patients by the MELD/PELD score was circulated for public comment in August 2000, with a special open Public Forum held in Dallas in September 2000 to get additional input from the community. Based on this input, additional validation of MELD against other sets of patients with liver disease was accomplished,6 and several other refinements were made. Patients with diagnoses such as stage I or I1 hep- atocellular carcinoma (HCC), who are thought to be good vious studies had confirmed the accuracy of this risk model candidates for for liver transplantation but who do not have a predicting mortality for patients undergoing Transjugular high risk of death attributable to liver failure and therefore

3 The New Liver Allocation System 853 will not have increased MELD (or PELD) scores, were con- individuals with increased muscle mass. However, an sidered and a mechanism was developed to give these patients equivalent mortality risk scores based on available literaanalysis of the relationship between creatinine clearance (using the Cockrofi-Gault Formula) and serum creatiture.7-1 l Additional refinements included accommodating nine among patients on the liver waiting list showed dialysis-dependent patients for whom serum creatinine values that, except for serum creatinine values >4, there was may be misleading in the MELD model, refining blood type an inverse linear correlation between creatinine and compatibility policies in the absence of categorical urgency definitions, adjusting the system to incorporate already-apcreatinine clearance (data not shown) and there was an proved policies that preferentially direct pediatric donor insignificant difference between men and women. In a organs to pediatric recipients, and redefining regional peer review processes already in place to ensure that patients for separate analysis performed by the Scientific Registry for Transplant Recipients (SRTR) group, substituting whom listing centers wish to request increased priority above that defined by the MELD/PELD score will have a peer review mechanism by which this may be accomplished. Recertification policies were defined to ensure that current data are used for assigning priority status, and transition pol- icies to ensure that no patients are disadvantaged by this change were developed. In November 2001, the UNOY OPTN Board of Directors reviewed the final plan and approved it for implementation. The new system went into effect on February 27,2002. Results MELD Score Analysis of multiple cohorts of adult patients showed that the MELD score consistently yielded a high degree of concordance12 to predict rnortality5>l3 for all types of adult patients with chronic liver disease. Moreover, when additional clinical variables such as spontaneous bacterial peritonitis, variceal bleeding, ascites, or encephalopathy were added to the model, there was no improvement in the predictive valueof the MELD score.6 This is consistent with other reports suggesting that mortality is more related to the severity of the underlying liver disease than the occurrence of one of these clinical events Liver disease etiology orig- was MELD scores of >40 no additional priority. This inally included as an independent predictor of mortality allows centers to attempt transplantation in candidates in the original MELD model reported by Malinchoc et a14; however, when this variable is omitted from the MELD model, the concordance for predicting mortalwho were thought to have a reasonable chance of success despite their extremely high risk, but does not give extra priority above a MELD score of 40 to achieve this. ity remains extremely high and is little different when compared with the model that includes the diagnosis variable.6 Thus, the diagnosis variable was not included to remove any etiologic discrimination in the allocation policy. Accordingly, the equation used to determine the MELD score for this policy proposal includes a constant (0.64) so that scores from this model will be comparable with scores obtained from the original MELD model (Table 1). The public comment process identified a concern that creatinine may not adequately reflect actual renal function and may potentially give undue priority to creatinine clearance in place of the serum creatinine variable in the MELD model did not improve its accuracy for predicting mortality. l7 Therefore, creatinine clearance does not seem to offer an advantage for refining mortality risk, nor does using the serum creatinine variable seem to unduly advantage men over womes. Approximately 3% of candidates on the liver transplant waiting list require dialysis. Because serum creatinine values for these patients may be artificially low, the new policy assigns all patients on dialysis a serum creatinine value of 4 mg/dl for calculation of MELD scores. Additionally, because elevated serum creatinine level is a good independent predictor of poor outcome after transplantation, *,l9 candidates with serum creatinine values greater than 4.0 were not given additional priority to avoid futile transplants. Thus, serum creatinine values are capped at 4.0 mg/dl and candidates with higher values, or those on dialysis, have their serum creatinine values set to 4.0mg/dL for calculation of the MELD score. By using an accurate measure of liver disease severity to prioritize the most ill candidates, more futile transplants might be performed under this new system. A consensus was reached to cap the MELD score at a maximum of 40 points and give candidates with Integration of MELD and PELD The MELD and PELD scores were both derived from separate cohorts of patients, neither of which were initially derived from the actual liver transplant waiting list. Analyses of the liver transplant waiting list by the SRTR indicated that the mortality rates for adult and pediatric patients were quite similar20 (Fig. 1). When these investigators plotted mortality versus MELD/ PELD scores, one cansee that for a given MELD/ PELD score, children have a lower mortality risk21 (Fig. 2). Thus when pediatric and adult patients interspersed

4 854 Freeman et a1 1.o Figure1.Comparisonof pediatric (N = 2,660) and adult (N = 32,861) SW- P vival curves for patients on *e transplant the US liver z between list waiting 1 / 1/97 and 12/31/00 withfol- Adults low-up through 5/31/01. P =.001 by Cox regression adjusting for year of waiting list entry Days on the waiting list, children have an advantage in that their mortality risk will be lower as they reach the top of the list relative to adults with comparable MELD scores. This is in keeping with previous UNOYOPTN policy that recognizes that children suffering from ESLD also suffer other lifelong developmental complications. Previous UNOS/OPTN policy stipulated that organs from donors < 18 years of age must be preferentially offered to children within the identical medical urgency category. Under this new policy, pediatric donor organs are allocated first to pediatric and then to adult status 1 candidates. If no local or regional status 1 candidates accept the pediatric liver offer, the organ is allocated to any pediatric candidate with >50% a mortality risk as defined by PELD (PELD score 246) in the local allocation area. Adult patients with >50% mortality risk (MELD score of 33) have next priority, and then all pediatric candidates with PELD scores <46 will have preference over all other adult candidates (Table 2). If the pediatric organ cannot be placed at the local or regional level, the organ is offered to national pediatric status 1 candidates, followed by national adult status I candidates, then to any national pediatric candidate with >50% a mortality risk, then to any national adult with >50% mortality risk, then to any other pediatric candidate, and finally to any adult candidate. Waiting Time Waiting time is carried backward but not forward, and is used only to rank patients with equal MELD/PELD scores. Thus, when a candidate has been waiting for 2 weeks at a MELD/PELD score of 10 and then moves to a MELD/PELD score of 15 because of a change in his or her laboratory values, the 2 weeks of TW is not carried forward and a new waiting time clock starts for that patient at the MELD/PELD score of 15. If, after 2 additional weeks at 15, the patient s laboratory values improve such that the MELD/PELD score now calculates to 12, the weeks 2 of TW at 15 is carried backward and added to the time accrued at the MELD score of 12. This time only affects priority ranking if there are other patients with MELD/PELD scores equal to 12 90% - 80% - 70% - Figure 2. Comparison of MELD and PELD mortality risks derived from 649 pediatric patients in the SPLIT database and 1,672 - adult patients added to the 30% waiting list between 5/4/01 20% - and 1 O/ 1 O/O2. 10% % \ PELD: SPLIT patients Severity Score - MELD: National waitlist

5 The New Liver Allocation System Local pediatric status 1 2. Local adult status 1 3. Regional pediatric status 1 4. Regional adult status 1 5. Local pediatric with >50% mortality by PELD score 6. Local adult with >50% mortality by MELD score 7. Local pediatric <50% mortality by PELD score 8. Local adult with <50% mortality by MELD score 9. Regional pediatric with >50% mortality 10. Regional adult with >50% mortality 1 1. Regional pediatric with < 50% mortality by PELD score 12. Regional adult with <50% mortality by MELD score 13. National pediatric status National adult status National pediatric with >50% mortality 16. National adult with >50% mortality 17. National pediatric with <50% mortality 18. National adult with <50% mortality when an organ is offered. The patient with the longest TW at that score, including any time accrued at any score above that score, is offered the organ first. Indications for Liver Transplantation Not Addressed by MELD/PELD and the Role of Regional Review Boards Members of the LDSS committee recognized that there are several conditions for which urgency for transplantation is not based on the likelihood of death but more driven byprogressionofdisease to a point beyond which a transplantation can be performed with success. Patients with HCC represent the largest group in this category. The LDSS committee examined as much natural history data for HCC as possible to try and develop a statistical model on which to base an allocation scoring system for patients with HCC. They focused on using the probability of progression beyond stage I1 cancer as an end point, rather than the probability of death from ESLD. This effort is consistent with current UNOS/OPTN policy, which recognizes that patients with stage I and I1 HCC should receive some priority beyond their degree of underlying liver disease because ample data suggest that liver transplantation offers these patients the best chance for cure and long-term survival rates not radically different than those of the recipient without malignant disease.9~'~ However, there are no good studies using actual data, and analyses of the probability of tumor progression have only been accomplished using statistical models. Thus, the committee suggested that patients presenting with a stage I lesion have an estimated risk of progression beyond stage I1 disease of 15%, and patients presenting with stage I1 lesions have an estimated risk of progression beyond stage I1 of 30%. These progression risks equate to mortality risks in the MELD score system equal to a score of 24 and 29, respectively. Because these patients receiveincreased priority on the list, the committee thought that, in the interest of fairness, these patients should have their diagnoses reasonably secure before allowing the assignment of additional priority points. Accordingly, new more rigorous diagnostic criteria have been developed that candidates must meet to receive the increase priority. To qualify for this increased priority, the HCC candidate must have a thorough assessment to evaluate the number and size of tumors and to rule out any extrahepatic spread and/or macrovascular involvement (i.e., portal or hepatic veins). A biopsy is not mandatory, but the lesion must meet established imaging criteria using either computed tomography or magnetic resonance scans. For the initial assessment before listing, patients must also have a chest computed tomography and bone scans that rule out the presence of metastatic lesions and at least one of the following: a tumor 1 cm in size with a blush corresponding to the area of suspicion seen on the above imaging studies, an alpha- fetoprotein level of >200, an arteriogram confirming a tumor, a biopsy confirming HCCA, chemoembolization of lesion, and radio frequency, cryoablation, or chemical ablation of the lesion. The plan also allows centers to apply for an additional risk points (1 point corresponding to a 10% increase in risk)every 3 months if there is a repeat computed tomography or magnetic resonance scan documenting that the lesion has not progressed beyond stage 11. Regional Review Boards review each application for HCC priority. They also review other requests for increased priority for conditions such as hepatopulmonary ~yndrome,~~>~3 familial amyloidosis, or metabolic liver disease in which the MELD/PELD scoring system may not adequately prioritize good candidates for transplantation because they do not have ESLD. Recertification Schedule and Timeliness of Laboratory Values for Calculation of MELD/PELD One of the serious deficiencies of the previous allocation system was that there was little ability to reflect changes in individual patients' conditions as their liver disease progressed. The new plan provides a graduated schedule for required recertification of laboratory values to ensure a good representation of the severity of disease

6 856 Freemun et ul 3. ~ ~ fschedde i for ~ ~~~ ~ ~ Seora o ~ MELD Adult Patient Reassessment and Recertification Schedule Status 1 Status recertification every 7 days Laboratory values must be no older than 48 hours MELD Score L 25 Status recertification every 7 days Laboratory values must be no older than 48 hours Score I 24 but > 18 Status recertification every 1 month Laboratory values must be no older than 7 days Score I 18 but 2 11 Status recertification every 3 months Laboratory values must be no older than 14 days Score 5 10 but > 0 Status recertification every 12 months Laboratory values must be no older than 30 days PELD Pediatric Patient Reassessment and Recertification Schedule Status 1 Status recertification every 7 days Laboratory values must be no older than 48 hours PELD Score L 25 Status recertification every 7 days Laboratory values must be no older than 48 hours Score I 24 but > 18 Status recertification every 1 month Laboratory values must be no older than 7 days Score 5 18 but 2 11 Status recertification every 3 months Laboratory values must be no older than 14 days Score 5 10 but > 0 Status recertification every 12 months Laboratory values must be no older than 30 days of all patients on the list (Table 3). Centers are required to recerti@ patients with the highest MELD/PELD scores at least weekly to maintain that level of score. If centersfail to meet the recertification requirements, patients will revert to the previous lower MELD/PELD score or a score of 6 if no previous score has been recorded. Discussion Although this new policy is based on a considerable amount of evidence that these risk scores accurately predict the risk of death, transforming a mathematical model into allocation policy has proven to be a complicated process. Furthermore, there are limitations to this initial plan that must be constantly addressed in the future. The MELD and PELD scores were derived and validated against cohorts of patients whose fates depended on liver allocation under the previous allocation policy. Under the new policy, different individuals will be prioritized so that those receiving transplants and those dying on the waiting list will have different characteristics than individuals in the original validation cohorts. Therefore, it is possible that with experience, the MELD and PELD equation coefficients will need to be altered in the future. Furthermore, addition of other variables might refine and improve the accuracy of these risk models. Potential variables to be considered must continue to be as objective as possible and should not be discriminatory. Inclusion of some simple clinical dichotomous variables in the MELD score, such asdialysis or endotracheal incubation, or some calculated variable, such as the rate of change in the MELD score, might be considered for improvements in the future. As experience is gained with this system, practitioners will accumulate previously unavailable data regarding the natural history of hepatocellular cancer. This will be extremely valuable data for constructing better risk models to predict the progression of HCC and will allow a better estimation of how much priority these patients should receive. Also, with time, more data will be available to better estimate disease severity for the other indications for liver transplantation that are not well served by the MELD/PELD scores. Important in this process will be the identification of appropriate end points, similar to the risk of progression beyond stage I1 disease for HCC, on which to base risk models. Inherent in the implementation of any new system is the commitment to constantly evaluate its results and update the system as frequently as possible. Although there are preliminary results from a limited trial that suggest a continuous disease score that emphasizes waiting time can reduce waiting list mortality without diminution of posttransplantation survival,24 experience over several years will be necessary to accurately determine whether this system is achieving these goals. Policymakers will also be interested in how more subtle outcome measures such as cost and quality of life are affected and how these should beaccounted for in future improvements of the system. Experience suggests that regional differences in waiting list dynamics will be important for adjusting the national system to local idiosyncrasies of donor availability, competition among programs, and prevailing practice patterns. There are preliminary data suggesting that there is a small but significant amount of regional variation in the MELD scores at which patients receive transplants and at which they are removed from the list

7 The New Liver Allocation System 857 because of death.25 This suggests that it may be necessary to develop specific policies at the regional level to be sure that the correct amount of priority is given to cases that are not accounted for by the MELD/PELD equations, such as HCC or hepatopulmonary syndrome. Therefore, Regional Review Boards, centers, and patients will find it essential to have frequent feedback about the range of MELD/PELD scores likely to result in an organ offer. This will be extremely important in the future so that it may become possible to make adjustments in organ availability across boundaries. With the elimination of TW as a major determinant for ranking liver transplant candidates, it is likely that revision of the minimum listing criteria for placement on the liver transplant list will be necessary. Patients without a high likelihood of dying in a 3-month period may not need to be on the list. There should be much less pressure to place patients on the list to accrue TW because TW plays such a minor role. Also, the large number of patients placed in the inactive category may be considerably reduced because they will not need to maintain their Tw while in the inactive status to achieve a high priority when their condition improves enough to resume an active status on the list. The goal for the future is to have the system be responsive to evidence-based assessments of risk and adjust it as ofien as the data suggest is prudent. In addition, development of posttransplantation risk models will be equally important. These can be added to pretransplantation risk models so that organs will be directed to those individuals with the highest risk of dying without a transplant but who have the highest chance of success with the liver transplant. This would lead to maximization of outcomes for patients entering the liver transplant waiting list. Implementation of this new system is the first step in evidence-based policymaking, but absent a supply of organs to meet the demand, it must continue to evolve along the same objective, evidence-based approach to best serve our patlents. References Federal Register. [FR Doc l] 42 CFR Part 12 l, April 2, 1998: Components of the CTP score employed in the previous liver allocation policy. Available at: Accessed July 31, Committee on Organ Procurement and Transplantation Policy. Organ Procurement and Transplantation: Assessing Current Policies and the Potential Impact of the DHHS Final Rule. Washington, DC: National Academy Press, 1999:82. Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, ter- Borg PL. A model to predict poor survival in patients undergoing Transjugular intrahepatic portosystemic shunts. Hepatology 2000;31: Wiesner RH, McDiarmid SV, Kamath PS, Edwards EB, Malinchoc M, Kremers WK, et al. MELD and PELD: Application of survival models to liver allocation. 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The Emory prospective randomized trial: Selective versus nonselective shunt to control variceal bleeding: Ten year follow-up. Ann Surg1985;201: Wolfe R, Merion R, Dykstra D, Rasmussen C. Analysis for Data Request from the OPTN Liver and Intestinal Committee of 08/01 /O 1. Scientific Registry Transplant of Recipients. Available at: Accessed July 31, Bennett-Guerrero E, Feierman DE, Barclay GR, Parides MK, Sheiner PA, Mythen MG, et al. Preoperative and intraoperative predictors of postoperative morbidity, poor graft function, and early rejection in 190 patients undergoing liver transplantation. Arch Surg 2001;136: Gayowski T, Marino IR, Singh N, Doyle H, Wagener M, Fung JJ, Starzl TE. Orthotopic liver transplantation in high-risk patients: Risk factors associated with mortality and infectious morbidity. Transplantation 1998;65: Wolfe R, Merion R, Dykstra D, Rasmussen C. Analysis for Data Request from the OPTN Liver and Intestinal Committee of 08/0 /O 1 1 Final Report. 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8 858 Freeman et a1 ients. Available at: Accessed July 31, Krom RAF, Wiesner RH. Hepatopulmonary syndrome with progressive hypoxemia is an indication for liver transplant. Mayo 21. Wolfe R, Merion R, Dykstra D, Rasmussen C. Analysis for Data Request from the OPTN Liver and Intestinal Committee of /10/01 Final Report. Scientific Registry of Transplant Recip- Clin Rev 1997;72: Freeman RB, Rohrer RJ, Katz E, Lewis WD, Jenkins RL, Cosimi AB, et al. Preliminary results of a liver allocation plan using a ients.availableat: July 31, continuous medical severity score that de-emphasizes waiting time. Liver Transpl200 1;7: Krowka MJ. Hepatopulmonary syndrome: recent literature 25. Freeman RB, Harper A, Edwards EB. There is minimal variation (1997 to 1999) and implications for liver transplantation. Liver among UNOS regions in prospectively collected MELD scores Transpl2000;6(suppl l):s Krowka MJ, Porayko MK, Plevak DJ, Pappas SC, Steers JL, for patients receiving liver transplants. 251s. Am J Transpl 2002,2: