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Combination of liver biopsy with MELD-XI scores for post-transplant outcome prediction in patients with advanced heart failure and suspected liver dysfunction.

ABSTRACT: Functional and structural liver abnormalities may be found in patients with advanced heart failure (HF). The Model of End-Stage Liver Disease Excluding INR (MELD-XI) score allows functional risk stratification of HF patients on and off anti-coagulation awaiting heart transplantation (HTx), but these scores may improve or worsen depending on bridging therapies and during time on the waiting list. Liver biopsy is sometimes performed to assess for severity of fibrosis. Uncertainty remains whether biopsy in addition to MELD-XI improves prediction of adverse outcomes in patients evaluated for HTx.Sixty-eight patients suspected of advanced liver disease underwent liver biopsy as part of their HTx evaluation. A liver risk score (fibrosis-on-biopsy + 1) × MELD-XI was generated for each patient.Fifty-two patients were listed, of whom 14 had mechanical circulatory support (MCS). Thirty-six patients underwent transplantation and 27 patients survived ?1 year post-HTx (74%, as compared with 88% average 1-year survival in HTx patients without suspected liver disease; p < 0.01). Survivors had a lower liver risk score at evaluation for HTx (31.0 ± 20.4 vs 65.2 ± 28.6, p < 0.01). A cut-point of 45 for liver risk score was identified by receiver-operating-characteristic (ROC) analysis. In the analysis using Cox proportional hazards models, a liver risk score ?45 at evaluation for HTx was associated with greater risk of death at 1 year post-HTx compared with a score of <45 in both univariable (HR 3.94, 95% CI 1.77-8.79, p < 0.001) and multivariable (HR 4.35, 95% CI 1.77-8.79, p < 0.001) analyses. Patients who died <1 year post-HTx had an increased frequency of acute graft dysfunction (44.4% vs 3.7%, p = 0.009), longer ventilation times (55.6% vs 11.1%, p = 0.013) and severe bleeding events (44.4% vs 11.1%, p = 0.049). The liver risk score at evaluation for HTx also predicted 1-year mortality after HTx listing (p < 0.001).Patients with HF and advanced liver dysfunction are high-risk HTx candidates. Liver biopsy in addition to MELD-XI improves risk stratification of patients with advanced HF and suspected irreversible liver dysfunction.

SUBMITTER: Farr M

PROVIDER: S-EPMC4941637 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Combination of liver biopsy with MELD-XI scores for post-transplant outcome prediction in patients with advanced heart failure and suspected liver dysfunction.

Farr Maryjane M Mitchell James J Lippel Matthew M Kato Tomoko S TS Jin Zhezhen Z Ippolito Paul P Dove Lorna L Jorde Ulrich P UP Takayama Hiroo H Emond Jean J Naka Yoshifumi Y Mancini Donna D Lefkowitch Jay H JH Schulze P Christian PC

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 20141223 7

<h4>Background</h4>Functional and structural liver abnormalities may be found in patients with advanced heart failure (HF). The Model of End-Stage Liver Disease Excluding INR (MELD-XI) score allows functional risk stratification of HF patients on and off anti-coagulation awaiting heart transplantation (HTx), but these scores may improve or worsen depending on bridging therapies and during time on the waiting list. Liver biopsy is sometimes performed to assess for severity of fibrosis. Uncertaint ...[more]

PMID: 25851466

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Project description:BackgroundControversy exists regarding the best predictive model of liver transplant waiting list (WL) mortality. Models for end-stage liver disease-glomerular filtration rate assessment in liver disease (MELD-GRAIL) and MELD-GRAIL-Na were recently described to provide better prognostication, particularly in females. We evaluated the performance of these scores compared to MELD and MELD-Na.MethodsConsecutive patients with cirrhosis waitlisted for liver transplant from 1998 to 2017 were examined in this single-center study. The primary outcome was 90-d WL mortality. MELD, MELD-Na, MELD-GRAIL, and MELD-GRAIL-Na at the time of WL registration were compared. Model discrimination was assessed with area under the receiver operating characteristic curves and Harrell's C-index after fitting Cox models. Model calibration was examined with Grønnesby and Borgan's modification of the Hosmer-Lemeshow formula and by comparing predicted/observed outcomes across model strata.ResultsThe study population comprised 1108 patients with a median age of 53.5 (interquartile range 48-59) y and male predominance (74.9%). All models had excellent areas under the receiver operating characteristic curves for the primary outcome (MELD 0.89, MELD-Na 0.91, MELD-GRAIL 0.89, MELD-GRAIL-Na 0.89; all comparisons P > 0.05). Youden index cutoffs for 90-d mortality were as follows: MELD, 19; MELD-Na, 22; MELD-GRAIL, 18; and MELD-GRAIL-Na, 17. Variables associated with 90-d mortality on multivariable Cox regression were sodium, bilirubin, creatinine, and international normalized ratio. There were no differences in model discrimination using Harrell's C-index. All models were well calibrated; however, divergence between observed and predicted mortality was noted with scores ≥25.ConclusionThere were no demonstrable differences in discrimination or calibration of GRAIL-based models compared with MELD or MELD-Na in our cohort. This suggests that GRAIL-based models may not have meaningful improvements in discriminatory ability when applied to other settings.

Project description:ImportanceLiver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on 4 laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex.ObjectiveTo use laboratory values stored in electronic health records to describe population-level sex differences in all MELD laboratory values (in healthy individuals and patients with liver disease) and propose a sex adjustment.Design, setting, and participantsA retrospective cohort study was conducted from March 2019 to April 2020 to evaluate sex differences in laboratory values in liver transplant patients, patients with liver disease who did not undergo transplant, and healthy controls. Primary analyses were conducted in Vanderbilt University Medical Center (VUMC)'s deidentified electronic health record system. Replication analyses were conducted in the All of Us Research Program. Simulations of a sex-adjusted sodium-adjusted MELD (MELDNa) score were completed using liver transplant waiting list data from the liver simulated allocation modeling system. Patients who regularly used VUMC with measurements for any MELDNa component laboratory were included in the analyses. Analysis took place from November 2019 to March 2021.ExposuresElectronic health record-reported sex.Main outcomes and measureCreatinine, bilirubin, international normalized ratio, and sodium levels.ResultsThe VUMC sample was composed of 623 931 individuals (359 976 [57.7%] female) with a median (IQR) age of 44 (23-61) years. All component MELDNa laboratory values and calculated MELDNa scores yielded significant sex differences within VUMC (mean [SD] creatinine: male, 0.99 [0.39] mg/dL; female, 0.79 [0.30] mg/dL; P < .001; bilirubin: male, 0.76 [0.83] mg/dL; female, 0.58 [0.64] mg/dL; P < .001; international normalized ratio of prothrombin rate: male, 1.24 [0.42]; female, 1.20 [0.40]; P < .001; sodium: male, 139.00 [2.36] mEq/L; female, 139.03 [2.28] mEq/L; P < .001), resulting in MELDNa scoring that disadvantaged female individuals. This pattern persisted when the sample was divided into healthy controls, individuals with liver disease who did not undergo transplant, and patients who did undergo liver transplant. Female transplant patients had a greater number of decompensation traits (mean [SD]: male, 1.34 [1.11]; female, 1.60 [1.09]; P = .005), despite having lower MELDNa scores (mean [SD]: male, 21.72 [6.11]; female, 20.21 [6.15]; P = .005), indicating MELDNa scores are not accurately representing disease severity in female individuals. In simulations, the sex-adjusted MELDNa score modestly increased female transplant rate and decreased overall death.Conclusions and relevanceThese results demonstrate pervasive sex differences in all laboratory values used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol.

Project description:In the era of the "sickest first" policy, patients with very high model for end-stage liver disease (MELD) scores have been increasingly admitted to the intensive care unit with the expectation that they will receive a liver transplant (LT) in the absence of improvement on supportive therapies. Such patients are often admitted in a context of acute-on-chronic liver failure with extrahepatic failures. Sequential assessment of scores or classification based on organ failures within the first days after admission help to stratify the risk of mortality in this population. Although the prognosis of severely ill cirrhotic patients has recently improved, transplant-free mortality remains high. LT is still the only curative treatment in this population. Yet, the increased relative scarcity of graft resource must be considered alongside the increased risk of losing a graft in the initial postoperative period when performing LT in "too sick to transplant" patients. Variables associated with poor immediate post-LT outcomes have been identified in large studies. Despite this, the performance of scores based on these variables is still insufficient. Consideration of a patient's comorbidities and frailty is an appealing predictive approach in this population that has proven of great value in many other diseases. So far, local expertise remains the last safeguard to LT. Using this expertise, data are accumulating on favourable post-LT outcomes in very high MELD populations, particularly when LT is performed in a situation of stabilization/improvement of organ failures in selected candidates. The absence of "definitive" contraindications and the control of "dynamic" contraindications allow a "transplantation window" to be defined. This window must be identified swiftly after admission given the poor short-term survival of patients with very high MELD scores. In the absence of any prospect of LT, withdrawal of care could be discussed to ensure respect of patient life, dignity and wishes.

Project description:PurposeMELD-XI, an adapted version of Model for End-stage Liver Disease (MELD) score excluding INR, was reported to predict outcomes e.g. in patients with acute heart failure. We aimed to evaluate MELD-XI in critically ill patients admitted to an intensive care unit (ICU) for prognostic relevance.MethodsA total of 4381 medical patients (66±14 years, 2862 male) admitted to a German ICU between 2004 and 2009 were included and retrospectively investigated. Admission diagnoses were e.g. myocardial infarction (n = 2034), sepsis (n = 694) and heart failure (n = 688). We divided our patients in two cohorts basing on their MELD-XI score and evaluated the MELD-XI score for its prognostic relevance regarding short-term and long-term survival. Optimal cut-offs were calculated by means of the Youden-Index.ResultsPatients with a MELD-XI score >12 had pronounced laboratory signs of organ failure and more comorbidities. MELD-XI >12 was associated with an increase in short-term (27% vs 6%; HR 4.82, 95%CI 3.93-5.93; p<0.001) and long-term (HR 3.69, 95%CI 3.20-4.25; p<0.001) mortality. In a univariate Cox regression analysis for all patients MELD-XI was associated with increased long-term mortality (changes per score point: HR 1.06, 95%CI 1.05-1.07; p<0.001) and remained to be associated with increased mortality after correction in a multivariate regression analysis for renal failure, liver failure, lactate concentration, blood glucose concentration, oxygenation and white blood count (HR 1.04, 95%CI 1.03-1.06; p<0.001). Optimal cut-off for the overall cohort was 11 and varied remarkably depending on the admission diagnosis: myocardial infarction (9), pulmonary embolism (9), cardiopulmonary resuscitation (17) and pneumonia (17). We performed ROC-analysis and compared the AUC: SAPS2 (0.78, 95%CI 0.76-0.80; p<0.0001) and APACHE (0.76, 95%CI 0.74-0.78; p<0.003) score were superior to MELD-XI (0.71, 95%CI 0.68-0.73) for prediction of mortality.ConclusionsThe easily calculable MELD-XI score is a robust and reliable tool to predict both intra-ICU and long-term mortality in critically ill medical patients admitted to an ICU. Optimal cut-off values for MELD-XI scores seem to depend on the primary disease and need to be validated in future prospective studies. Compared to SAPS2 and APACHE score, MELD-XI lacks precision but might have comparable and even additive value, as it is easily available and independent of subjective values.

Dataset Information

Combination of liver biopsy with MELD-XI scores for post-transplant outcome prediction in patients with advanced heart failure and suspected liver dysfunction.

Publications

Combination of liver biopsy with MELD-XI scores for post-transplant outcome prediction in patients with advanced heart failure and suspected liver dysfunction.

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