MELD is MELD is MELD? Transplant center–level variation in waitlist mortality for candidates with the same biological MELD

Recently, model for end-stage liver disease (MELD)-based liver allocation in the United States has been questioned based on concerns that waitlist mortality for a given biologic MELD (bMELD), calculated using laboratory values alone, might be higher at certain centers in certain locations across the country. Therefore, we aimed to quantify the center-level variation in bMELD-predicted mortality risk. Using Scientific Registry of Transplant Recipients (SRTR) data from January 2015 to December 2019, we modeled mortality risk in 33 260 adult, first-time waitlisted candidates from 120 centers using multilevel Poisson regression, adjusting for sex, and time-varying age and bMELD. We calculated a "MELD correction factor" using each center's random intercept and bMELD coefficient. A MELD correction factor of +1 means that center's candidates have a higher-than-average bMELD-predicted mortality risk equivalent to 1 bMELD point. We found that the “MELD correction factor” median (IQR) was 0.03 (−0.47, 0.52), indicating almost no center-level variation. The number of centers with “MELD correction factors” within ±0.5 points, and between ±0.5–± 1, ±1.0–±1.5, and ±1.5–±2.0 points was 62, 41, 13, and 4, respectively. No centers had waitlisted candidates with a higher-than-average bMELD-predicted mortality risk beyond ±2 bMELD points. Given that bMELD similarly predicts waitlist mortality at centers across the country, our results support continued MELD-based prioritization of waitlisted candidates irrespective of center.     

Addition of serum sodium into the MELD score predicts waiting list mortality better than MELD alone.

In this study, we investigated the prognostic value of serum sodium and hyponatremia (< or =130 mEq/L) in 262 cirrhotic patients consecutively listed, 19 of which died (7%), 175 survived (67%), and 68 underwent liver transplantation (26%) during 3 months of follow-up. Hyponatremia was present in 63% of patients who died, compared to 13% of those who survived (P < .001), whereas the proportion with elevated creatinine (> or =1.4 mg/dL) was low and similar in both groups (10.5 vs. 3%). Prevalence of hyponatremia was higher than that of elevated serum creatinine across all model for end-stage liver disease (MELD) categories. Using logistic regression, hyponatremia and serum sodium were significant predictors of mortality with concordance statistics (c-statistics) .753 for hyponatremia, .784 for sodium, .894 for MELD, .905 for MELD plus hyponatremia (P = .006 vs. MELD alone), and .908 for MELD plus serum sodium (P = .026 vs. MELD alone). Risk of death across all MELD scores was higher for patients with hyponatremia than without hyponatremia. Cox regression considering data within 6 months of follow-up yielded qualitatively similar results, with hyponatremia being a significant predictor of greater mortality risk with an odds ratio of 2.65 (P = .015). Each increase of 1 mEq/L of serum sodium level was associated with a decreased odds ratio of .95 (P = .048). Our results indicate that hyponatremia appears to be an earlier and more sensitive marker than serum creatinine to detect renal impairment and / or circulatory dysfunction in patients with advanced cirrhosis. In conclusion, addition of serum sodium to MELD identified a subgroup of patients with poor outcome in a more efficient way than MELD alone and significantly increased the efficacy of the score to predict waitlist mortality.     

Improving liver allocation: MELD and PELD

On February 27, 2002, the liver allocation system changed from a status-based algorithm to one using a continuous MELD/PELD severity score to prioritize patients on the waiting list. Using data from the Scientific Registry of Transplant Recipients, we examine and discuss several aspects of the new allocation, including the development and evolution of MELD and PELD, the relationship between the two scoring systems, and the resulting effect on access to transplantation and waiting list mortality. Additional considerations, such as regional differences in MELD/PELD at transplantation and the predictive effects of rapidly changing MELD/PELD, are also addressed.
Death or removal from the waiting list for being too sick for a transplant has decreased in the MELD/PELD era for both children and adults. Children younger than 2 years, however, still have a considerably higher rate of death on the waiting list than adults.
A limited definition of ECD livers suggests that they are used more frequently for patients with lower MELD scores.     

MELD/PELD: one year later

The liver allocation policy in the United States was changed on February 27, 2002, to a continuous scale with almost no weight given to time waiting on the list. This was based on the dissatisfaction with the old categorical system and an understanding that waiting time as not a good discriminator of medical urgency. To assess the effects of this change, liver allocation results for the first 6 months of this new system (February 27, 2002, to August 30, 2002, era 2) with the corresponding 6 month period 1 year earlier (February 27, 2001, to August 30, 2001, era 1) were compared. Fewer registrations on the waiting list, fewer removals from the waiting list because of death or "too sick," and an increase in the number of cadaveric transplants under the new system were observed. Patients with hepatocellular cancer received additional priority with the new policy and there was a significant increase in the number of candidates transplanted with this diagnosis in era 2. Early posttransplant patient survival has not changed under the new system. Although there are many areas for improvement, which will be addressed in future refinements, the new US liver allocation plan has provided a more objective, patient-specific system to better rank waiting liver transplant candidates.     

MELD Exceptions and Rates of Waiting List Outcomes

Model for End-stage Liver Disease (MELD)-based allocation of deceased donor livers allows exceptions for patients whose score may not reflect their true mortality risk. We hypothesized that organ procurement organizations (OPOs) may differ in exception practices, use of exceptions may be increasing over time, and exception patients may be advantaged relative to other patients. We analyzed longitudinal MELD score, exception and outcome in 88 981 adult liver candidates as reported to the United Network for Organ Sharing from 2002 to 2010. Proportion of patients receiving an HCC exception was 0-21.4% at the OPO-level and 11.9-18.8% at the region level; proportion receiving an exception for other conditions was 0.0%-13.1% (OPO-level) and 3.7-9.5 (region-level). Hepatocellular carcinoma (HCC) exceptions rose over time (10.5% in 2002 vs. 15.5% in 2008, HR = 1.09 per year, p<0.001) as did other exceptions (7.0% in 2002 vs. 13.5% in 2008, HR = 1.11, p<0.001). In the most recent era of HCC point assignment (since April 2005), both HCC and other exceptions were associated with decreased risk of waitlist mortality compared to nonexception patients with equivalent listing priority (multinomial logistic regression odds ratio [OR] = 0.47 for HCC, OR = 0.43 for other, p<0.001) and increased odds of transplant (OR = 1.65 for HCC, OR = 1.33 for other, p<0.001). Policy advantages patients with MELD exceptions; differing rates of exceptions by OPO may create, or reflect, geographic inequity.     

Impact of Recipient MELD Score on Resource Utilization

The model for end stage liver disease (MELD) system prioritizes deceased donor organs to the sickest patients who historically require higher healthcare expenditures. Limited information exists regarding the association of recipient MELD score with resource use. Adult recipients of a primary liver allograft (n = 222) performed at a single center in the first 27 months of the MELD system were analyzed. Costs were obtained for each recipient for the 12 defined categories of resource utilization from the time of transplant until discharge. True (calculated) MELD scores were used. Inpatient transplant costs were significantly associated with recipient MELD score (r = 0.20; p = 0.002). Overall 1-year patient survival was 85.0% and was not associated with MELD score (p = 0.57, log rank test). Recipient MELD score was significantly associated with costs for pharmacy, laboratories, radiology, dialysis and physical therapy. Multivariate linear regression revealed that MELD score was most strongly associated with cost compared to other demographic and clinical factors. Recipient MELD score is correlated with transplant costs without significantly impacting survival.     

MELD and prediction of post-liver transplantation survival.

The model for end-stage liver disease (MELD) was developed to predict short-term mortality in patients with cirrhosis. It has since become the standard tool to prioritize patients for liver transplantation. We assessed the value of pretransplant MELD in the prediction of posttransplant survival. We identified adult patients who underwent liver transplantation at our institution during 1991-2002. Among 2,009 recipients, 1,472 met the inclusion criteria. Based on pretransplant MELD scores, recipients were stratified as low risk (< or = 15), medium risk (16-25), and high risk (>25). The primary endpoints were patient and graft survival. Mean posttransplant follow-up was 5.5 years. One-, 5- and 10-year patient survival was 83%, 72%, and 58%, respectively, and graft survival was 76%, 65%, and 53%, respectively. In univariable analysis, patient and donor age, patient sex, MELD score, disease etiology, and retransplantation were associated with posttransplantation patient and graft survival. In multivariable analysis adjusted for year of transplantation, patient age >65 years, donor age >50 years, male sex, and retransplantation and pretransplant MELD scores >25 were associated with poor patient and graft survival. The impact of MELD score >25 was maximal during the first year posttransplant. In conclusion, older patient and donor age, male sex of recipient, retransplantation, and high pretransplant MELD score are associated with poor posttransplant outcome. Pretransplant MELD scores correlate inversely with posttransplant survival. However, better prognostic models are needed that would provide an overall assessment of transplant benefit relative to the severity of hepatic dysfunction.     

30例肝移植病例MELD分析

目的探讨终末期肝病模型（MELD）评分评估终末期肝病患者行肝移植术后,受者短期预后、肝移植的手术时机以及MELD与肝脏病理的关系。方法对30例肝移植病例进行回顾性分析,比较术后随访30天后存活组（12例）与死亡组（18例）的术前MELD评分,以MELD分值25和30为界线将病例分组,比较存活率以及肝脏病理,分析大块、亚大块肝细胞坏死与非大块、亚大块肝细胞坏死病例的MELD分值。结果所有患者术前MELD评分平均值为28．92±13．45,术后随访3个月总生存率为40％,其中存活组与死亡组术前MELD评分分别为21．56±11．83和33．82±12．43（P〈0．05）;以MELD评分25为界将患者分为两组,术后3个月存活率为63．6％和26．3％（P〈0．05）;以MELD评分30为界将患者分为两组,术后3个月存活率为53．3％和26．7％（P〉0．05）：大块、亚大块肝细胞坏死组与非大块、亚大块肝细胞坏死组患者术前MELD值相比有显著差异,分别为22．38±12．69和33．28±12．41（P〈0．05）。结论MELD评分可评估肝移植受术者的短期预后,肝移植受者MELD评分值在25分时比30分时行肝移植术更有意义,MELD评分与肝细胞坏死面积有关。     

Impact of MELD on Waitlist Outcome of Retransplant Candidates

Under the current allocation system for liver transplantation (LTx), primary and retransplantation (ReTx) are treated identically. The aims of this study were (1) to compare the risk of death between ReTx and primary LTx candidates at a given MELD score and (2) to gauge the impact of the MELD‐based allocation system on the waitlist outcome of ReTx candidates. Based on data of all waitlist registrants in the United States between 2000 and 2006, unique adult patients with chronic liver disease were identified and followed forward to determine mortality within six months of registration. There were a total of 45,943 patients waitlisted for primary LTx and 2081 registered for ReTx. In the MELD era (n = 30,175), MELD was significantly higher among ReTx candidates than primary LTx candidates (median, 21 vs. 15). Within a range of MELD scores where most transplantation took place, mortality was comparable between ReTx and primary candidates after adjusting for MELD. The probability for LTx increased significantly following implementation of the MELD‐based allocation in both types of candidates. We conclude that by and large, primary and ReTx candidates fare equitably under the current MELD‐based allocation system, which has contributed to a significant increase in the probability of LTx.     

Prognosis after liver transplantation predicted by preoperative MELD score

The model for end-stage liver disease (MELD) has been an excellent predictor of 3-month mortality among cirrhotic patients awaiting orthotopic liver transplantation (OLT). The aim of this study was to evaluate whether the preoperative MELD score predicts short-term prognosis after OLT. We enrolled 98 adult liver transplant patients performed at our center from January 2001 to December 2002. In univariate analysis of risk factors for death within 3 and 6 months after liver transplantation, serum total bilirubin, creatinine, MELD score, hyponatremia with ascites, Child-Turcotte-Pugh (CTP) score were statistically significant parameters (P < .05). By logistic regression, none of the risk factors were subjected to multivariate analysis showed statistical significance. The odds ratios of the MELD score, hyponatremia with ascites, CTP score within 3 months were 0.997, 1.151, and 0.726 with 95% confidence intervals of [0.899, 1.105], [0.102, 12.959], and [0.389, 1.352], respectively. The odds ratio of MELD score, hyponatremia with ascites, CTP score within 6 months were 0.996, 0.914, and 0.764, with 95% confidence intervals of [0.901, 1.102], [0.089, 9.369], and [0.417, 1.401], respectively. Although MELD score has been a good predictor of short-term prognosis before OLT, MELD did not show an influence on the short-term prognosis after liver transplantation in this study.     

MELD and other predictors of survival after liver transplantation

Abstract: Background: This study examined how reliable is the pre‐transplant model for end‐stage liver disease (MELD) score in predicting post‐transplantation survival and analyzed variables associated with patient survival. Methods: A cohort study was conducted. Receiver operating characteristic curve c‐statistics were used to determine the ability of MELD score to predict mortality. The Kaplan–Meier (KM) method was used to analyze survival as a function of time regarding the MELD score and Child‐Turcotte‐Pugh (CTP) category. The Cox model was employed to assess the association between baseline risk factors and mortality. Results: Recipients and donors were mostly male, with a mean age of 51.6 and 38.5 yr, respectively (n = 436 transplants). The c‐statistic values for three‐month patient mortality were 0.60 and 0.61 for MELD score and CTP category, respectively. KM survival at three, six and 12 months were lower in those who had a MELD score ≥21 or were CTP category C. Multivariate analysis revealed that recipient age ≥65 yr, MELD ≥ 21, CTP C category, bilirubin ≥ 7 mg/dL, creatinine ≥ 1.5 mg/dL, platelet transfusion, hepatocellular carcinoma, and non‐white color donor skin were predictors of mortality. Conclusions: Severe pre‐transplant liver disease, age ≥ 65, non‐white skin donor, and hepatocellular carcinoma are associated with poor outcome.     

The Economic Impact of MELD on Liver Transplant Centers

Adoption of the model for end stage liver disease (MELD) system prioritized patients awaiting liver transplant (LT) by severity of illness including progressive renal dysfunction. Unfortunately, current reimbursement for LT is not adjusted by severity of illness or need for simultaneous liver-kidney transplantation (LKT). This study examines hospital cost and reimbursement for LT and LKT to determine the effect of MELD on transplant center (TC) financial outcomes given current reimbursement practices as well as DRG outlier threshold limits. LT was performed for 86 adults prior to and 127 following the implementation of MELD. Between the eras, there was a substantial increase in the average laboratory MELD score (17.1 to 20.7 p=0.004) and percentage of LKTs performed (5.8% to 17.3% p=0.01). Increasing MELD score was associated with higher costs ($4309 per MELD point p<0.001) and decreasing TC net income ($1512 per MELD point p<0.001). In patients not achieving the Medicare outlier status, predicted net loss was $17,700 for high-MELD patients and $19,133 for those needing LKT. In conclusion, contractual reimbursement agreements that are not indexed by severity of disease may not reflect the increased costs resulting from the MELD system. Even with outlier thresholds, Medicare reimbursement is inadequate resulting in a net loss for the TC.     

Acute renal failure after liver transplantation in MELD era

Model for End-Stage Liver Disease (MELD) score was used in our center from 2003 to assess the position of orthotopic liver transplantation (OLT) candidates on a waiting list. A key component of MELD score in the assessment of the degree of the illness is renal function. In this study, we measured the effects of this new scoring system on renal function and therapeutic strategies. We evaluated the incidence of acute renal function (ARF) after OLT requiring renal replacement therapy (hemofiltration or hemodialysis) in two patient groups: 240 transplanted before MELD era and 224 after the introduction of this parameter to select candidates. ARF occurred in 8.3% of patients in the pre-MELD group versus 13% in the MELD group, while the mortality rates were 40% and 27%, respectively. The creatinine level before OLT seemed to be a good predictor of ARF (P < .001), and blood transfusion rates (P < .05) as well as intraoperative diuresis (P < .05). In our analysis we did not observe a correlation between MELD score and postoperative ARF.     

MELD and Other Factors Associated with Survival after Liver Transplantation

Allocation of cadaveric livers for transplantation in the United States is now based on the severity of illness as determined by the model for end-stage liver disease (MELD) score, a function of bilirubin, creatinine and international normalized ratio (INR). The aim of our study was to determine the association of various pre-transplant risk factors, including the MELD score, on patient survival after orthotopic liver transplantation (OLT). The medical records of 499 consecutive patients (233 female, 266 males, mean age 50.9 +/- 10.6 years) undergoing cadaveric OLT at our institution between June 1990 and February 1998 were reviewed. In the 407 patients alive at the latest contact, follow-up was 4.7 years, with a minimum of 20 months (maximum of 9.4 years). Variables considered for analysis included MELD score, age, pre-transplant renal dysfunction requiring dialysis, Child-Pugh classification, underlying liver disease, diabetes mellitus, and heart disease (ischemic/valvular/other). There were 92 deaths during follow-up. In univariate analysis, the MELD score, renal failure requiring hemodialysis pre-OLT, age > 42 years, and underlying etiology of liver disease were significantly associated with death during long-term follow-up. In multivariate models, age, underlying etiology of liver disease and renal failure requiring hemodialysis were independent predictors of death after OLT.