Project description:Background & aimsAcute-on-chronic liver failure (ACLF) is one of the most deadly, prevalent, and costly diseases in Asia. However, no prognostic model has been developed that is based specifically on data gathered from Asian patients with ACLF. The aim of the present study was to quantify the survival time of ACLF among Asians and to develop a prognostic model to estimate the probability of death related to ACLF.MethodsWe conducted a retrospective observational cohort study to analyze clinical data from 857 patients with ACLF/pre-ACLF who did not undergo liver transplantation. Kaplan-Meier and Cox proportional hazards regression model were used to estimate survival rates and survival affected factors. The area under the receiver operating characteristic curve (auROC) was used to evaluate the performance of the models for predicting early mortality.ResultsThe mortality rates among patients with pre-ACLF at 12 weeks and 24 weeks after diagnosis were 30.5% and 33.2%, respectively. The mortality rates among patients with early-stage ACLF at 12 weeks and 24 weeks after diagnosis were 33.9% and 37.1%, respectively. The difference in survival between pre-ACLF patients and patients in the early stage of ACLF was not statistically significant. The prognostic model identified 5 independent factors significantly associated with survival among patients with ACLF and pre-ACLF: the model for end-stage liver disease (MELD) score; age, hepatic encephalopathy; triglyceride level and platelet count.ConclusionThe findings of the present study suggest that the Chinese diagnostic criteria of ACLF might be broadened, thus enabling implementation of a novel model to predict ACLF-related death after comprehensive medical treatment.
Project description:ObjectiveTo identify factors that accurately predict 1-year survival for liver transplant recipients with a MELD score ≥40.BackgroundAlthough transplant is beneficial for patients with the highest acuity (MELD ≥40), mortality in this group is high. Predicting which patients are likely to survive for >1 year would be medically and economically helpful.MethodsThe Scientific Registry of Transplant Recipients database was reviewed to identify adult liver transplant recipients from 2002 through 2016 with MELD score ≥40 at transplant. The relationships between 44 recipient and donor factors and 1-year patient survival were examined using random survival forests methods. Variable importance measures were used to identify the factors with the strongest influence on survival, and partial dependence plots were used to determine the dependence of survival on the target variable while adjusting for all other variables.ResultsWe identified 5309 liver transplants that met our criteria. The overall 1-year survival of high-acuity patients improved from 69% in 2001 to 87% in 2016. The strongest predictors of death within 1 year of transplant were patient on mechanical ventilator before transplantation, prior liver transplant, older recipient age, older donor age, donation after cardiac death, and longer cold ischemia.ConclusionsLiver transplant outcomes continue to improve even for patients with high medical acuity. Applying ensemble learning methods to recipient and donor factors available before transplant can predict survival probabilities for future transplant cases. This information can be used to facilitate donor/recipient matching and to improve informed consent.
Project description:BackgroundThe gene-signature-model for end stage liver disease (gs-MELD) score has been shown to be a strong predictor of 6-month survival in severe alcoholic hepatitis (AH). Currently, only a few studies have evaluated the long-term prognosis of patients with severe AH.AimTo assess the prognostic value of the gs-MELD score at 5 years in patients with severe AH.MethodsForty-eight consecutive patients with AH (25 males, median age 52 years [95% IC: 48-56]) were included.ResultsThe median gs-MELD score was 2.6 (95% CI: 2.2-3.0). According to the gs-MELD score, 22 patients (46%) were considered to have a poor prognosis. During a median follow-up of 29 months (95% CI: 4-43), 19 patients (40%) were abstinent and 24 patients (50%) died. At 5 years, rates of survival were 61% (95% CI: 41-81) and 26% (95% CI: 11-55) in patients with low and high gs-MELD scores (P = .001), and 81% (95% CI: 58-96) and 22% (95% CI: 10-47) in abstainers and in consumers (P < .001) respectively. In multivariable competing risk regression modelling, gs-MELD score (subdistribution hazard ratio: 5.78, 95% CI: 2.17-15.38, P < .001) and recurrent alcohol consumption (subdistribution hazard ratio: 12.18, 95% CI: 3.16-46.95, P < .001) were independently associated with 5-year mortality.ConclusionsBoth gs-MELD score and alcohol consumption drive AH long-term prognosis. The gs-MELD score may guide the development of molecularly targeted therapies in AH.
Project description:BackgroundHigh score of model for end-stage liver diseases (MELD) before liver transplantation (LT) indicates poor prognosis. Artificial liver support system (ALSS) has been proved to effectively improve liver and kidney functions, and thus reduce the MELD score. We aim to evaluate whether downgrading MELD score could improve patient survival after LT.Methodology/principal findingsOne hundred and twenty-six LT candidates with acute-on-chronic hepatitis B liver failure and MELD score ≥30 were included in this prospective study. Of the 126 patients, 42 received emergency LT within 72 h (ELT group) and the other 84 were given ALSS as salvage treatment. Of the 84 patients, 33 were found to have reduced MELD score (<30) on the day of LT (DGM group), 51 underwent LT with persistent high MELD score (N-DGM group). The median waiting time for a donor was 10 for DGM group and 9.5 days for N-DGM group. In N-DGM group there is a significantly higher overall mortality (43.1%) than that in ELT group (16.7%) and DGM group (15.2%). N-DGM (vs. ECT and DGM) was the only independent risk factor of overall mortality (P = 0.003). Age >40 years and the interval from last ALSS to LT >48 h were independent negative influence factors of downgrading MELD.Conclusions/significanceDowngrading MELD for liver transplant candidates with MELD score ≥30 was effective in improving patient prognosis. An appropriate ALSS treatment within 48 h prior to LT is potentially beneficial.
Project description:The model for end-stage liver disease (MELD) score is used to stratify candidates for liver transplantation based on objective measures of disease severity. MELD has been validated as a predictor of wait-list mortality in transplantation candidates and has been postulated as a predictor of post-transplant survival. The purpose of this study was to examine the predictive value of the pre-transplantation MELD score on post-transplant survival from relevant existing studies. A systematic review and critical appraisal was performed using Cochrane guidelines. PubMed, the Cochrane Library, Embase, and Web of Science were searched for articles published in the English language since 2005 using a structured search strategy. There were 3058 discrete citations identified and screened for possible inclusion. Any study examining the relationship between pre-transplant MELD and post-transplant survival in the general transplant population was included. Thirty-seven studies met these criteria and were included in the review. Studies were all case series that typically involved stratified analyses of survival by MELD. They represented 15 countries and a total of 53,691 patients. There was significant clinical heterogeneity in patient populations across studies, which precluded performance of a meta-analysis. In 15 studies, no statistically significant association between MELD and post-transplant survival was found. In the remaining 22, some association was found. Eleven studies also measured predictive ability with c-statistics. Values were below 0.7 in all but two studies, suggesting poor predictive value. In summary, while the majority of studies reported an association between pre-transplantation MELD score and post-transplant survival, they represented a low level of evidence. Therefore, their findings should be interpreted conservatively.
Project description:BackgroundThe prevalence of heart failure (HF) is rising and the only corrective treatment is cardiac transplantation. Advanced HF is associated with congestive hepatopathy and progressive functional and ultrastructural changes of the liver. We hypothesized that hepatic dysfunction is associated with impaired clinical outcome after heart transplantation.MethodsData of 617 adult patients (75% men, mean age 53 ± 12 years, mean BMI 25 ± 4, mean ejection fraction 19 ± 9%) undergoing orthotopic heart transplantation (OHT) were analyzed retrospectively. Deviation from institutional normal ranges was used to define abnormal liver function. Standard Model for End-stage Liver Disease (MELD) scores were calculated and a modified MELD score with albumin replacing INR (modMELD) was created to eliminate the confounding effects of anti-coagulation.ResultsBefore OHT, AST, ALT and total bilirubin were elevated in 20%, 18% and 29% of the population, respectively. Total protein and albumin were decreased in 25% and 52% of the population, respectively. By 2 months post-transplantation, percentages of individuals with pathologic values decreased significantly, except for ALT, total protein and albumin, all of which took longer to normalize. Individuals with a higher pre-transplantation MELD or modMELD score had worse outcome 30 days post-transplant and reduced long-term survival over a 10-year follow-up.ConclusionsIn this large, single-center retrospective study, we demonstrated the dynamics of liver dysfunction after cardiac transplantation and that elevated MELD scores indicating impaired liver function are associated with poor clinical outcome after OHT. Thus, pre-operative liver dysfunction has a significant impact on survival of patients after cardiac transplantation.
Project description:BackgroundWithout available curative therapies for delta hepatitis (hepatitis delta virus [HDV]), hepatic decompensation and hepatocellular carcinoma (HCC) among HDV patients often necessitates liver transplantation (LT). The objective of this study was to evaluate outcomes of LT among hepatitis B virus (HBV)/HDV patients in the United States.MethodsWe performed the first US-based retrospective study of patients who underwent LT for HDV compared with HBV (monoinfection) in the years 2002-2019. We evaluated posttransplant survival and predictors of survival.ResultsWe identified a total of 152 HBV/HDV and 5435 HBV patients who underwent LT. HDV patients were younger at transplant (52 versus 55, P < 0.001), less commonly Asian (16% versus 36%, P < 0.001), more likely to be HCV Ab positive (42% versus 28%, P < 0.001), and less likely to be listed for LT with HCC (38% versus 51%, P = 0.001), more likely to have ascites (73% versus 64%, P = 0.019), had worse coagulopathy (mean INR 2.0 versus 1.82, P = 0.04), and were more likely to receive a HCV-positive donor organ (7% versus 3%, P = 0.001). Post-LT overall survival and graft survival were similar between HDV and HBV patients, including among patients with HCC. Older age, HCV coinfection, HCC, and higher model for end-stage liver disease at transplant were associated with higher posttransplant mortality.ConclusionsHDV patients were sicker and more likely to be listed for LT for decompensated disease compared with HBV patients. Post-LT survival was similar between HDV and HBV patients, in contrast to prior international studies that suggested worse post-LT survival in HBV patients due to higher rates of HBV reactivation.
Project description:BackgroundPatients with hepatocellular carcinoma (HCC) tend to be referred for liver transplantation (LT) at an early stage of cirrhosis, with lower pre-LT Model of End-Stage Liver Disease (MELD) scores. We investigated the impact of high MELD scores on post-LT outcomes in patients with HCC and validated the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR).Patients and methodThis retrospective single-center cohort study enrolled 230 patients with HCC who underwent LDLT from 2004-2019 in our institute. We defined a high MELD score as ≥20.ResultsThe MELD < 20 and MELD ≥ 20 groups comprised 205 and 25 cases, respectively. Although there was no significant difference in disease-free survival between the two groups (p = 0.629), the incidence of septic shock (p = 0.019) was significantly higher in the high MELD group. The one-, three-, and five-year overall survival rates were not significantly different between the two groups (p = 0.056). In univariate analysis, a high pre-LT NLR was associated with poorer survival in the high MELD group (p = 0.029, hazard ratio [HR]: 1.07, 90% confidence interval [CI]: 1.02-1.13). NLR cut-off values of ≥10.7 and <10.7 were predictive of mortality, with an AUC of 0.705 (90% CI: 0.532-0.879). The one-, three-, and five-year post-LT survival rates were significantly higher among the recipients with an NLR < 10.7 than those with an NLR ≥ 10.7 (p = 0.005).ConclusionsPre-LT MELD score ≥ 20 was associated with a higher risk of developing post-LT septic shock and mortality. The pre-LT serum NLR is a useful predictive factor for clinical outcomes in patients with HCC with high MELD scores.
Project description:Background and aimsLipoprotein Z (LP-Z) is an abnormal free cholesterol (FC)-enriched LDL-like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP-Z in alcohol-associated hepatitis (AH) and interrogate the biology behind its formation.Approach and resultsWe measured serum levels of LP-Z using nuclear magnetic resonance spectroscopy, a well-established clinical assay. Serum levels of LP-Z were significantly elevated in four AH cohorts compared with control groups, including heavy drinkers and patients with cirrhosis. We defined a Z-index, calculated by the ratio of LP-Z to total apolipoprotein B-containing lipoproteins, representing the degree of deviation from normal VLDL metabolism. A high Z-index was associated with 90-day mortality independent from the Model for End-Stage Liver Disease (MELD) and provided added prognosticative value. Both a Z-index ≤ 0.6 and a decline of Z-index by ≥0.1 in 2 weeks predicted 90-day survival. RNA-sequencing analyses of liver tissues demonstrated an inverse association in the expression of enzymes responsible for the extrahepatic conversion of VLDL to LDL and AH disease severity, which was further confirmed by the measurement of serum enzyme activity. To evaluate whether the FC in LP-Z could contribute to the pathogenesis of AH, we found significantly altered FC levels in liver explant of patients with AH. Furthermore, FC in reconstituted LP-Z particles caused direct toxicity to human hepatocytes in a concentration-dependent manner, supporting a pathogenic role of FC in LP-Z.ConclusionsImpaired lipoprotein metabolism in AH leads to the accumulation of LP-Z in the circulation, which is hepatotoxic from excessive FC. A Z-index ≤ 0.6 predicts 90-day survival independent from conventional biomarkers for disease prognostication.
Project description:BackgroundPredictors of poor outcome associated with variceal bleeding remain suboptimal. In patients with cirrhosis, serum lactate combined with Model for End-Stage Liver Disease (MELD-LA) improved prediction across heterogeneous populations. However, prognostic properties have not yet been assessed in the context of variceal bleeding.AimsWe aimed to evaluate the predictive performance of MELD-LA compared to MELD, lactate, and nadir hemoglobin in cirrhosis patients with variceal bleeding.MethodsIn this multicenter study, we identified 472 patients with variceal bleeding from a German primary cohort (University Hospitals Hamburg/Frankfurt/Cologne), and two independent external validation cohorts [Veterans Affairs (VA), Baylor University]. Discrimination for 30-day mortality was analyzed and scores were compared. MELD-LA was evaluated separately in validation cohorts to ensure consistency of findings.ResultsIn contrast to nadir hemoglobin, MELD and peak-lactate at time of bleeding were significantly higher in 30-day non-survivors in the primary cohort (p = 0.708; p < 0.001). MELD-LA had excellent discrimination for 30-day mortality (AUROC 0.82, 95% CI 0.76-0.88), better than MELD and peak-lactate (AUROC 0.78, 95% CI 0.71-0.84; AUROC 0.73, 95% CI 0.66-0.81). MELD-LA predicted 30-day mortality independently of age, sex, severity of liver disease and vasopressor support (HR 1.29 per 1-point-increase of MELD-LA; 95% CI 1.19-1.41; p < 0.001). Similarly, MELD-LA demonstrated excellent discrimination for 30-day mortality in the VA (AUROC = 0.86, 95% CI 0.79-0.93) and Baylor cohort (AUROC = 0.85, 95% CI 0.74-0.95).ConclusionsMELD-LA significantly improves discrimination of short-term mortality associated with variceal bleeding, compared to MELD, peak-lactate and nadir hemoglobin. Thus, MELD-LA might represent a useful and objective marker for risk assessment and therapeutic intervention in patients with variceal bleeding.