Ann M. Harper

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 years 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 Transpl 2004;10:7–15.)

OPTN/SRTR 2015 Annual Data Report: Liver.

ABSTRACT  The current liver allocation system, introduced in 2002, decreased the importance of waiting time for allocation priorities; the number of active wait‐listed candidates and median waiting times were immediately reduced. However, the total number of adult wait‐listed candidates has increased since 2002, and median waiting time has increased since 2006. Pretransplant mortality rates have been stable, but the number of candidates withdrawn from the list as being too sick to undergo transplant nearly doubled between 2009 and 2011. Deceased donation rates have remained stable, with an increasing proportion of expanded criteria donors. Living donation has decreased over the past 10 years. Transplant outcomes remain robust, with continuously improving graft survival rates for deceased donor, living donor, and donation after circulatory death livers. Numbers of new and prevalent pediatric candidates on the waiting list have decreased. Pediatric pretransplant mortality has decreased, most dramatically for candidates aged less than 1 year. The transplant rate has increased since 2002, and is highest in candidates aged less than 1 year. Graft survival continues to improve for pediatric recipients of deceased donor and living donor livers. Incidence of acute rejections increases with time after transplant. Posttransplant lymphoproliferative disorder remains an important concern in pediatric recipients.

Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States.

A national conference was held to better characterize the long‐term outcomes of liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) and to assess whether it is justified to continue the policy of assigning increased priority for candidates with early‐stage HCC on the transplant waiting list in the United States. The objectives of the conference were to address specific HCC issues as they relate to liver allocation, develop a standardized pathology report form for the assessment of the explanted liver, develop more specific imaging criteria for HCC designed to qualify LT candidates for automatic Model for End‐Stage Liver Disease (MELD) exception points without the need for biopsy, and develop a standardized pretransplant imaging report form for the assessment of patients with liver lesions. At the completion of the meeting, there was agreement that the allocation policy should result in similar risks of removal from the waiting list and similar transplant rates for HCC and non‐HCC candidates. In addition, the allocation policy should select HCC candidates so that there are similar posttransplant outcomes for HCC and non‐HCC recipients. There was a general consensus for the development of a calculated continuous HCC priority score for ranking HCC candidates on the list that would incorporate the calculated MELD score, alpha‐fetoprotein, tumor size, and rate of tumor growth. Only candidates with at least stage T2 tumors would receive additional HCC priority points. Liver Transpl 16:262–278, 2010.

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. (Liver Transpl 2004;10:36–41.)

OPTN/SRTR 2013 Annual Data Report: Liver: OPTN/SRTR 2013 Annual Data Report: Liver

During 2013, 10,479 adult candidates were added to the liver transplant waiting list, compared with 10,185 in 2012; 5921 liver transplants were performed, and 211 of the transplanted organs were from living donors. As of December 31, 2013, 15,027 candidates were registered on the waiting list, including 12,407 in active status. The most significant change in allocation policy affecting liver waitlist trends in 2013 was the Share 35 policy, whereby organs from an entire region are available to candidates with model for end‐stage liver disease scores of 35 or higher. Median waiting time for such candidates decreased dramatically, from 14.0 months in 2012 to 1.4 months in 2013, but the effect on waitlist mortality is unknown. The number of new active pediatric candidates added to the liver transplant waiting list increased to 693 in 2013. Transplant rates were highest for candidates aged younger than 1 year (275.6 per 100 waitlist years) and lowest for candidates aged 11 to 17 years (97.0 per 100 waitlist years). Five‐year graft survival was 71.7% for recipients aged younger than 1 year, 74.9% for ages 1 to 5 years, 78.9% ages 6 to 10 years, and 77.4% for ages 11 to 17 years.

MELD score as a predictor of pretransplant and posttransplant survival in OPTN/UNOS status 1 patients

The Model for End‐Stage Liver Disease (MELD) score is predictive of survival and is used to prioritize patients with chronic liver disease patients for orthotopic liver transplantation (OLT). The aims of this study are (1) to assess the ability of MELD score at listing to predict pretransplant and posttransplant survival for nonchronic liver disease patients listed with the Organ Procurement and Transplantation Network/ United Network for Organ Sharing (OPTN/UNOS) as Status 1; and (2) to compare survival associated with 4 diagnostic groups within the Status 1 designation. The study population consisted of adult patients listed for OLT at Status 1 in the UNOS national database between November 1, 1999 and March 14, 2002 (N = 720). Events within 30 days of listing were analyzed using Kaplan‐Meier and Cox regression methodology. Patients meeting criteria for fulminant hepatic failure without acetaminophen toxicity (FHF‐NA, n = 312) had the poorest survival probability while awaiting OLT; this was negatively correlated with MELD score (P = .0001). These patients experienced the greatest survival benefit associated with OLT, with an estimated improvement of survival from about 58% to 91% (P < .0001). Patients listed for primary nonfunction within 7 days of OLT (n = 268) did not show mortality to be related to MELD score (P = .41) and did not show a significant association between survival and OLT (P = .68). In conclusion, liver allocation within the Status 1 designation may need to be further stratified by diagnosis, and MELD score may be useful for prioritizing FHF‐NA candidates. (HEPATOLOGY 2004;39:764–769.)

Hepatocellular Carcinoma Patients Are Advantaged in the Current Liver Transplant Allocation System

Patients with hepatocellular carcinoma (HCC) within Milan criteria receive priority on the liver transplant waiting list (WL) and compete with non‐HCC patients. Dropout from the WL is an indirect measure of transplant access. Competing risks (CR) evaluation of dropout for HCC and non‐HCC patients has not previously been reported. Patients listed between 16 March 2005 and 30 June 2008 were included. Probability of dropout was estimated using a CR technique as well as a Cox model for time to dropout. Overall, non‐HCC patients had a higher dropout rate from the WL than HCC patients (p < 0.0001). This was reproducible throughout all regions. In Cox regression, tumor size, model for end‐stage liver disease (MELD) score and alpha fetoprotein (AFP) were associated with increased dropout risk. Multivariable analysis with CR showed that MELD score and AFP, were most influential in predicting dropout for HCC patients. The index of concordance for predicting dropout with the CR was 0.70. HCC patients appear to be advantaged in the current allocation scheme based on lower dropout rates without regard to geography. A continuous score incorporating MELD, AFP and tumor size may help to prioritize HCC patients to better equate dropout rates with non‐HCC patients and equalize access.

Waiting list removal rates among patients with chronic and malignant liver diseases.

Equitable liver allocation should ensure that nonelective removal rates are fairly distributed among waiting candidates. We compared removal rates for adults entered with nonmalignant (NM) (N = 9379) and hepatocellular cancer (HCC) (N = 2052) diagnoses on the Organ Procurement and Transplantation Network (OPTN) list between April 30, 2003, and December 31, 2004. Unadjusted removal rates for NM vs. HCC diagnoses were 9.4% vs. 8.7%, 13.5% vs. 16.9% and 19.1% vs. 31.8% at 90, 180 and 365 days, respectively after listing. For NM candidates, model for end‐stage liver disease (MELD) score (RR = 1.16), age (RR = 1.03) and metabolic disease diagnoses (RR = 1.66) had higher risks of removal; and PSC (RR = 0.62) and alcoholic cirrhosis (RR = 0.82) had lower risks of removal. For HCC candidates, MELD score at listing (RR = 1.09), AFP (RR = 1.02), maximum tumor size (RR = 1.16) and age at listing (RR = 1.02) had increased risks of removal. The equation 1 − 0.920 exp[0.09369 (MELD at listing − 12.48) + 0.00193 (AFP − 97.4) + 0.1505 (maximum tumor size − 2.59) defined the probability of dropout for HCC candidates within 90 days of listing. We conclude that factors associated with the risk of removal for HCC are different from NM candidates, although MELD score at listing remains the most predictive for both groups. Liver transplant candidates with HCC may be prioritized using a risk score analogous to the MELD score.

Optimizing staging for hepatocellular carcinoma before liver transplantation: A retrospective analysis of the UNOS/OPTN database

Assignment of liver allocation priority for hepatocellular carcinoma is predicated on accurate imaging staging. We analyzed radiographically defined stage (radiologic stage [RS]) at listing and most recent extension and pathologic stage (PS) data from 789 liver transplant recipients for whom no pretransplant ablative treatment was given. There were no predetermined imaging or pathological protocols in this retrospective analysis of wait list data. Seventy‐two (9.1%), 690 (87.5%), and 27 (3.4%) were listed as stage 1, 2 and >2, respectively. Computed tomography (CT) scan alone (46.4%), magnetic resonance image scan alone (37.1%), ultrasound alone (1.3%), and multiple imaging studies (15.2%) were used with no difference in time to transplant for listing or most recent scan among the recipient groups. Overall accuracy (RS = PS) was 44.1% and was not different if original listing RS or most recent RS was used for comparison with PS. No one type of imaging technique had superior accuracy (P = 0.13); however, CT scan used alone or in combination compared to not being used at all, had higher odds of being accurate (odds ratio [OR] 1.38 [1.03‐1.84], P = 0.031). In addition, imaging done less than 90 days before transplant had higher odds of being accurate (OR 1.49 [1.06‐2.08], P = 0.019) as did RS = 2 or 3 (OR 5.56 [2.70‐11.11], P < 0.0001). We observed considerable variation in RS accuracy among the United Network for Organ Sharing and Organ Procurement and Transplantation Network regions that is unexplained. In conclusion, current imaging requirements for RS prior to liver transplantation are unacceptably inaccurate. Future policy should require more accurate modalities or combinations of techniques. Liver Transpl 12:1504‐1511, 2006.

Model for End-Stage Liver Disease (MELD) exception guidelines: Results and recommendations from the MELD exception study group and conference (MESSAGE) for the approval of patients who need liver transplantation with diseases not considered by the standard MELD formula

Richard B. Freeman Jr., Robert G. Gish, Ann Harper, Gary L. Davis, John Vierling, Leslie Lieblein, Goran Klintmalm, Jamie Blazek, Robert Hunter, and Jeffrey Punch Division of Transplantation, Department of Surgery, Tufts–New England Medical Center, Boston, MA; Departments of Medicine and Transplantation and the Division of Hepatology and Complex GI, Physicians Foundation, California Pacific Medical Center, San Francisco, CA; United Network for Organ Sharing, Richmond, VA; Baylor Regional Transplant Institute, Baylor University Medical Center, Dallas, TX; Department of Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA; Ochsner Multi-Organ Transplant Center, New Orleans, LA; and Department of Surgery, University of Michigan, Ann Arbor, MI