Prevalence and Outcomes of Multiple-Listing for Cadaveric Kidney and Liver Transplantation

Transplant candidates are permitted to register on multiple waiting lists. We examined multiple-listing practices and outcomes, using data on 81 481 kidney and 26 260 liver candidates registered between 7/1/95 and 6/30/00. Regression models identified factors associated with multiple-listing and its effect on relative rates of transplantation, waiting list mortality, kidney graft failure, and liver transplant mortality. Overall, 5.8% (kidney) and 3.3% (liver) of candidates multiple-listed. Non-white race, older age, non-private insurance, and lower educational level were associated with significantly lower odds of multiple-listing. While multiple-listed, transplantation rates were significantly higher for nearly all kidney and liver candidate subgroups (relative rate [RR]= 1.42-2.29 and 1.82-7.41, respectively). Waiting list mortality rates were significantly lower while multiple-listed for 11 kidney subgroups (RR = 0.22-0.72) but significantly higher for 7 liver subgroups (RR = 1.44-5.93), suggesting multiple-listing by healthier kidney candidates and sicker liver candidates. Graft failure was 10% less likely among multiple-listed kidney recipients. Multiple- and single-listed liver recipients had similar post-transplant mortality rates. Although specific factors characterize those transplant candidates likely to multiple-list, transplant access is significantly enhanced for almost all multiple-listed kidney and liver candidates.     

Pretransplant MELD Score As a Predictor of Outcome After Liver Transplantation for Chronic Hepatitis C

The Model of End-Stage Liver Disease (MELD) score, an accurate predictor of mortality in patients awaiting liver transplantation (OLTX), did not predict graft or patient survival in the post-transplant setting. Our aim was to test the model in patients who underwent OLTX for chronic hepatitis C. Two hundred and eighty-seven adult patients who underwent primary OLTX for chronic hepatitis C between December 1993 and September 1999 were studied from a prospectively maintained database. The group was stratified by MELD scores of less than 15, 15-24, and greater than 24. Patient survival, graft survival, and interval liver biopsy pathology were reviewed. Both patient and graft survival at 3, 6, and 12 months were significantly lower in the higher MELD score groups, as was patient survival at 24 months (p-values, 0.01-0.05). The difference in survival between the low, medium, and high MELD score groups increases in time. The survival without bridging fibrosis in the allograft at 1 year post-transplant was significantly lower with higher MELD scores (p = 0.037). The decrease in survival seen in hepatitis C patients with MELD scores greater than 24 raises questions of transplant suitability for these patients. Therapeutic modalities to decrease post-transplant graft injury in these patients should be explored.     

Validation of the Model for End-stage Liver Disease sodium (MELD-Na) score in the Eurotransplant region

The MELD score is used in the Eurotransplant (ET) region to allocate liver grafts. Hyponatremia in cirrhotic patients is an important predictor of death but is not incorporated in MELD. This study investigated the performance of the MELD-Na score for the ET region. All adult patients with chronic liver disease on the ET liver transplantation waiting list (WL) allocated through lab MELD scores were included. The MELD-corrected effect of serum sodium (Na) concentration at listing on the 90-day WL mortality was calculated using Cox regression. The MELD-Na performance was assessed with c-indices, calibration per decile and Brier scores. The reclassification from MELD to MELD-Na score was calculated to estimate the impact of MELD-Na-based allocation in the ET region. For the 5223 included patients, the risk of 90-day WL death was 2.9 times higher for hyponatremic patients. The MELD-Na had a significantly higher c-index of 0.847 (SE 0.007) and more accurate 90-day mortality prediction compared to MELD (Brier score of 0.059 vs 0.061). It was estimated that using MELD-Na would reduce WL mortality by 4.9%. The MELD-Na score yielded improved prediction of 90-day WL mortality in the ET region and using MELD-Na for liver allocation will very likely reduce WL mortality.     

边缘供肝应用于肝脏移植的研究进展

目的 探讨边缘供肝的种类及其在肝移植中的应用前景。方法 复习国外有关边缘供肝应用于临床肝移植的最新进展。结果 高龄供体、缺血时限较长供体、脑死亡供体和脂肪肝供体是几种临床意义较大的边缘供肝。结论 虽然边缘供肝的使用给肝脏移植带来负面效应，然而其能扩大供肝来源且疗效确切。     

Toward a Better Liver Graft Allocation That Accounts for Candidates With and Without Hepatocellular Carcinoma

In some countries where the Model for End‐Stage Liver Disease (MELD) score is used for graft allocation, selected patients with hepatocellular carcinoma (HCC) receive a fixed number of exception points at listing, and increasing priority on the list by accruing additional exception points at regular time intervals. This system originally aimed at balancing the risks of HCC patients of developing contraindications and of non‐HCC patients of dying before transplantation, is not ideal because it appears to offer an advantage to HCC patients, regardless of tumor characteristics and response to loco‐regional treatment. Scores modulated by HCC characteristics have been proposed. They are based on a more refined estimate of the risk of pretransplant drop‐out or of the posttransplant transplant benefit expressed as the life‐years gained for each graft. This review describes the newly proposed systems, and discusses their advantages and drawbacks. We believe that the current exception points allocation should be revised and that drop‐out‐equivalent or transplant benefit‐equivalent models should be studied further. As with all policy changes, these should be done under close monitoring that allows subsequent revisions.     

Sociodemographic Determinants of Waitlist and Posttransplant Survival Among End‐Stage Liver Disease Patients

While regional organ availability dominates discussions of distribution policy, community‐level disparities remain poorly understood. We studied micro‐geographic determinants of survival risk and their distribution across Donor Service Areas (DSAs). Scientific Registry of Transplant Recipients records for all adults waitlisted for liver transplantation 2002–2014 were reviewed. The primary exposure variables were county‐level sociodemographic risk, as measured by the Community Health Score (CHS), a previously‐validated composite index local health conditions, and distance to listing transplant center. Among 114 347 patients, the median CHS was 19.4 (range: 0–40). Compared the lowest risk counties (CHS 1–10), highest‐risk counties (CHS 31–40) had more black (14.6% vs. 5.4%), publicly insured (44.9% vs. 33.0), and remote candidates (34.0% vs. 15.1% living >100 miles away). Higher‐CHS candidates had greater waitlist mortality in Cox multivariable (HR 1.16 for CHS 31–40, 95% CI 1.11–1.21) and competing risks analysis (sHR 1.07, 95% CI 0.99–1.14). Post‐transplant survival was similar across CHS quartiles. Living >25 miles from the transplant center conferred excess mortality risk (sHR 1.08, 95% CI 1.03–1.12). Proposed distribution changes would disproportionately impact DSAs with more high‐CHS or distant candidates. Low‐income, rural and minority patients experience excess mortality while awaiting transplant, and risk disproportionately worse outcomes with reduced organ availability under current proposals.     

Regional Variation in Appropriateness of Non-Hepatocellular Carcinoma Model for End-Stage Liver Disease Exception

1. Download : Download high-res image (338KB)
2. Download : Download full-size image

     

Liver transplantation in patients with Caroli's disease and recurrent cholangitis

Caroli's disease is an uncommon congenital disorder of the intrahepatic biliary tree. It is characterized by multiple and segmental dilatations of the bile ducts. The clinical course of Caroli's disease is often complicated by recurrent episodes of bacterial cholangitis that seriously impair the patient's quality of life. Despite wide spectrum antimicrobial agents, medical treatment of cholangitis is frequently unsuccessful in patients with Caroli's disease due to the persistence of bacteria in dilatated bile ducts. Other therapies, including internal or external biliary drainages and various surgical or endoscopic procedures, have been used in the treatment of Caroli's disease, with poor results. There are no previous reports in the literature of liver transplantation for recurrent cholangitis in patients with Caroli's disease. We present two such cases, in which cholangitis is resolved. Received: 16 July 1996 Received after revision: 4 February 1997 Accepted: 5 February 1997     

Nonstandard Exception Requests Impact Outcomes for Pediatric Liver Transplant Candidates

Nonstandard exceptions requests (NSERs), in which transplant centers appeal on a case‐by‐case basis for Pediatric End‐Stage Liver Disease/Mayo End‐Stage Liver Disease points, have been highly utilized for pediatric liver transplant candidates. We evaluated whether NSE outcomes are associated with waitlist and posttransplant mortality. United Network for Organ Sharing (UNOS) Scientific Registry of Transplant Recipients data on pediatric liver transplant candidates listed in 2009–2014 were analyzed after excluding those granted automatic UNOS exceptions. Of 2581 pediatric waitlist candidates, 44% had an NSE request. Of the 1134 children with NSERs, 93% were approved and 7% were denied. For children 2–18 years at listing, NSER denial increased the risk of waitlist mortality or removal for being too sick (subhazard ratio 2.99, 95% confidence interval [CI] 1.26–7.07, p = 0.01 in multivariate analysis). For children younger than 2 years, NSER denial did not impact waitlist mortality/removal. Children with NSER approved had reduced risk of graft loss 3 years posttransplant in univariate but not multivariable analysis (odds ratio 0.73, 95% CI 0.53–1.01, p = 06). Those with NSER denial had a higher risk of posttransplant death than those with no NSER (hazard ratio 2.43, 95% CI 0.99–5.95, p = 0.05, multivariable analysis), but NSER approval did not impact posttransplant death. Further research on NSER utilization in pediatric liver transplant is needed to optimize organ allocation and outcomes for children.     

Adult Living Donor Liver Transplantation for Acute‐on‐Chronic Liver Failure in High–Model for End‐Stage Liver Disease Score Patients

The large volume of adult living donor liver transplantations (ALDLTs) at our center affords a unique opportunity to examine the impact of acute‐on‐chronic liver failure (ACLF) among high–Model for End‐Stage Liver Disease MELD score patients. From February 1998 to March 2010, 1958 cirrhotic recipients were analyzed to study the relationship between MELD scores and ALDLT outcomes. A total of 327 high‐MELD score recipients were categorized into ACLF and non‐ACLF groups, and their outcomes were compared. The 5‐year graft and patient survival in the high‐MELD group were 75.2% and 76.4%, respectively, which were significantly worse than the low and intermediate MELD groups. The presence of ACLF associated with higher MELD scores appeared to be the dominant factor responsible for the inferior results of patients with MELD score of 30–34 points. The 5‐year graft survivals in the ACLF group was 70.5% and in the non‐ACLF group it was 81.0% (p = 0.035). Therefore, ALDLT should be performed as soon as possible in high‐MELD score patients prior to ACLF development. Moreover, ACLF patients should be separately categorized when analyzing the outcomes of ALDLT. ALDLT for ACLF patients should not be discouraged because favorable outcomes can be expected through timely ALDLT and comprehensive management.     

One Size Does Not Fit All—Regional Variation in the Impact of the Share 35 Liver Allocation Policy

Allocation policies for liver transplantation underwent significant changes in June 2013 with the introduction of Share 35. We aimed to examine the effect of Share 35 on regional variation in posttransplant outcomes. We examined two patient groups from the United Network for Organ Sharing dataset; a pre–Share 35 group composed of patients transplanted between June 17, 2012, and June 17, 2013 (n = 5523), and a post–Share group composed of patients transplanted between June 18, 2013, and June 18, 2014 (n = 5815). We used Kaplan–Meier and Cox multivariable analyses to compare survival. There were significant increases in allocation Model for End‐stage Liver Disease (MELD) scores, laboratory MELD scores, and proportions of patients in the intensive care unit and on mechanical, ventilated, or organ‐perfusion support at transplant post–Share 35. We also observed a significant increase in donor risk index in this group. We found no difference on a national level in survival between patients transplanted pre–Share 35 and post–Share 35 (p = 0.987). Regionally, however, posttransplantation survival was significantly worse in the post–Share 35 patients in regions 4 and 10 (p = 0.008 and p = 0.04), with no significant differences in the remaining regions. These results suggest that Share 35 has been associated with transplanting “sicker patients” with higher MELD scores, and although no difference in survival is observed on a national level, outcomes appear to be concerning in some regions.     

Reuse of Auxiliary Liver Grafts in Second Recipients With Chronic Liver Disease

We describe the first cases of reuse of auxiliary liver grafts for orthotopic transplantation in chronic liver disease. A reduced liver graft (segments 2, 3, half of 4) was first transplanted auxiliary for acute liver failure using a new technique. After regeneration of both native liver and graft, the auxiliary graft was removed and immunosuppression discontinued in the first recipients. After informed consent of donors and recipients, both auxiliary grafts were then orthotopically transplanted into second recipients. Both grafts function normally. Reuse of auxiliary grafts may help to reduce the shortage or liver grafts available for transplantation.     

Justifying Nonstandard Exception Requests for Pediatric Liver Transplant Candidates: An Analysis of Narratives Submitted to the United Network for Organ Sharing, 2009–2014

Nonstandard exception requests (NSERs), for which transplant centers provide patient‐specific narratives to support a higher Model for End‐stage Liver Disease/Pediatric End‐stage Liver Disease score, are made for >30% of pediatric liver transplant candidates. We describe the justifications used in pediatric NSER narratives 2009–2014 and identify justifications associated with NSER denial, waitlist mortality, and transplant. Using United Network for Organ Sharing data, 1272 NSER narratives from 1138 children with NSERs were coded for analysis. The most common NSER justifications were failure‐to‐thrive (48%) and risk of death (40%); both associated with approval. Varices, involvement of another organ, impaired quality of life, and encephalopathy were justifications used more often in denied NSERs. Of the 25 most prevalent justifications, 60% were not associated with approval or denial. Waitlist mortality risk was increased when fluid overload or “posttransplant complication outside standard criteria” were cited and decreased when liver‐related infection was noted. Transplant probability was increased when the narrative mentioned liver‐related infections, and fluid overload for children <2 years old; it decreased when “posttransplant complications outside standard criteria” and primary sclerosing cholangitis were cited. This analysis provides novel insight and suggests targets for future consideration in outcomes research and exception criteria. Changes in the allocation system are needed to ensure equity and optimize outcomes for all pediatric candidates.     

Changes in International Normalized Ratio (INR) and Model for Endstage Liver Disease (MELD) Based on Selection of Clinical Laboratory

Priority for liver transplantation is based on the Model for Endstage Liver Disease (MELD) score, a mathematical function which includes international normalized ratio (INR). We present an analysis to determine the lab-to-lab variation in INR at 14 clinical laboratories across the United States. We performed a survey to identify representative clinical laboratories across the United States, where INR was measured in the determination of MELD score. Five 'standard' samples for INR were formulated and were sent to the 14 clinical laboratories to determine variation in INR and MELD score. Among the 14 clinical laboratories, the range in INR for the five samples was: sample 1 (1.2-2.0), sample 2 (1.4-2.5), sample 3 (1.7-3.4), sample 4 (1.9-3.7) and sample 5 (2.4-5.1). The range in calculated MELD score was: sample 1 (8-14), sample 2 (10-17), sample 3 (12-20), sample 4 (14-21) and sample 5 (16-25). The selection of the clinical laboratory used to determine INR may result in substantial changes in MELD score independent of severity-of-illness. These data suggest that further review of interlaboratory variation in MELD should be undertaken because of the potential impact on prioritization for liver transplantation.     

MELD评分系统在肝移植中的应用和意义

目的 讨论终末期肝病模型（MELD）的产生与发展，评价对肝移植的影响。方法回顾性分析MELD在肝移植应用中的有关文献。结果MELD广泛应用于预测和评定终末期肝病的严重程度及患者等待肝移植期间死亡危险度，以决定器官分配的优先顺序。结论MELD为新的评分系统，可减少患者等待肝移植的时间，客观地、精确地预测终末期肝病患者的短期生存率和死亡危险度，是较为理想的器官分配评分系统。