Left Ventricular Longitudinal Contractility Predicts Acute-on-Chronic Liver Failure Development and Mortality After Transjugular Intrahepatic Portosystemic Shunt.
ABSTRACT: Acute deterioration of liver cirrhosis (e.g., infections, acute-on-chronic liver failure [ACLF]) requires an increase in cardiac contractility. The insufficiency to respond to these situations could be deleterious. Left ventricular global longitudinal strain (LV-GLS) has been shown to reflect left cardiac contractility in cirrhosis better than other parameters and might bear prognostic value. Therefore, this retrospective study investigated the role of LV-GLS in the outcome after transjugular intrahepatic portosystemic shunt (TIPS) and the development of ACLF. We included 114 patients (48 female patients) from the Noninvasive Evaluation Program for TIPS and Their Follow-Up Network (NEPTUN) cohort. This number provided sufficient quality and structured follow-up with the possibility of calculating major scores (Child, Model for End-Stage Liver Disease [MELD], Chronic Liver Failure Consortium acute decompensation [CLIF-C AD] scores) and recording of the events (development of decompensation episode and ACLF). We analyzed the association of LV-GLS with overall mortality and development of ACLF in patients with TIPS. LV-GLS was independently associated with overall mortality (hazard ratio [HR], 1.123; 95% confidence interval [CI],1.010-1.250) together with aspartate aminotransferase (HR, 1.009; 95% CI, 1.004-1.014) and CLIF-C AD score (HR, 1.080; 95% CI, 1.018-1.137). Area under the receiver operating characteristic curve (AUROC) analysis for LV-GLS for overall survival showed higher area under the curve (AUC) than MELD and CLIF-C AD scores (AUC, 0.688 versus 0.646 and 0.573, respectively). The best AUROC-determined LV-GLS cutoff was -16.6% to identify patients with a significantly worse outcome after TIPS at 3 months, 6 months, and overall. LV-GLS was independently associated with development of ACLF (HR, 1.613; 95% CI, 1.025-2.540) together with a MELD score above 15 (HR, 2.222; 95% CI, 1.400-3.528). Conclusion: LV-GLS is useful for identifying patients at risk of developing ACLF and a worse outcome after TIPS. Although validation is required, this tool might help to stratify risk in patients receiving TIPS.
Project description:To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian patients.This is a prospective cohort study designed to assess the prognostic performance of the chronic liver failure-consortium (CLIF-C) acute decompensation score (CLIF-C AD) and CLIF-C acute-on-chronic liver failure score (CLIF-C ACLF), regarding 28-d and 90-d mortality, as well as to compare them to other prognostic models, such as Model for End-Stage Liver Disease (MELD), MELD Sodium (MELD-Na), Child-Pugh (CP) score, and the CLIF-C Organ Failure score (CLIF-C OF). All participants were adults with acute decompensation of cirrhosis admitted to the Emergency Department of a tertiary hospital in southern Brazil. Prognostic performances were evaluated by means of the receiver operating characteristic (ROC) curves, area under the curves (AUC) and 95%CI.One hundred and thirteen cirrhotic patients were included. At admission, 18 patients had acute-on-chronic liver failure (ACLF) and 95 individuals had acute decompensation (AD) without ACLF, of which 24 eventually developed ACLF during the course of hospitalization (AD evolving to ACLF group). The AD group had significantly lower 28-d (9.0%) and 90-d (18.3%) mortality as compared to the AD evolving to ACLF group and to the ACLF group (both P < 0.001). On the other hand, 28-d and 90-d mortalities were not significantly different between AD evolving to ACLF group and ACLF group (P = 0.542 and P = 0.708, respectively). Among patients with ACLF, at 28 d from the diagnosis, CLIF-C ACLF was the only score able to predict mortality significantly better than the reference line, with an AUC (95%CI) of 0.71 (95%CI: 0.54-0.88, P = 0.021). Among patients with AD, all prognostic scores performed significantly better than the reference line regarding 28-d mortality, presenting with similar AUCs: CLIF-C AD score 0.75 (95%CI: 0.63-0.88), CP score 0.72 (95%CI: 0.59-0.85), MELD score 0.75 (95%CI: 0.61-0.90), MELD-Na score 0.76 (95%CI: 0.61-0.90), and CLIF-C OF score 0.74 (95%CI: 0.60-0.88). The same occurred concerning AUCs for 90-d mortality: CLIF-C AD score 0.70 (95%CI: 0.57-0.82), CP score 0.73 (95%CI: 0.62-0.84), MELD score 0.71 (95%CI: 0.59-0.83), MELD-Na score 0.73 (95%CI: 0.62-0.84), and CLIF-C OF score 0.65 (95%CI: 0.52-0.78).This study demonstrated that CLIF-C ACLF is the best available score for the prediction of 28-d mortality among patients with ACLF. CLIF-C AD score is also useful for the prediction of mortality among cirrhotic patients with AD not fulfilling diagnostic criteria for ACLF, but it was not superior to other well-established prognostic scores.
Project description:BACKGROUND/AIMS:The MELD score was developed to predict survival after transjugular intrahepatic portosystemic shunt (TIPS) placement. Given changes in practice patterns and development of new prognostic tools in cirrhosis, we aimed to evaluate common models to predict mortality after TIPS placement. METHODS:Analysis of consecutive patients who underwent TIPS placement for ascites or bleeding. Performance to predict 90-day mortality was assessed by C statistic for six models (MELD, MELD-Na, CLIF-C ACLF, Child-Pugh, Platelet-Albumin-Bilirubin, and Emory score). Added predictive value to MELD score was assessed for univariate predictors of 90-day mortality. Stratified analysis by TIPS indication, emergent placement status, and TIPS stent type was performed. RESULTS:413 patients were analyzed (248 with variceal bleeding, 165 with refractory ascites). 90-day mortality was 27% (113/413). Mean MELD score was 15 ± 7.9. MELD score best predicted mortality for all patients (c = 0.779), for variceal bleeding (c = 0.844), and for emergent TIPS (c = 0.817). CLIF-C ACLF score best predicted mortality for refractory ascites (c = 0.707). Addition of sodium to the MELD score did not improve predictive value across multiple strata. Addition of hemoglobin improved MELD score's predictive value in variceal bleeding. Addition of age improved MELD score's predictive value in refractory ascites. CONCLUSIONS:MELD score best predicted 90-day mortality. Addition of sodium to the MELD score did not improve its performance, though mortality prediction was improved using Age-MELD for ascites and Hemoglobin-MELD for bleeding. An individualized risk stratification approach may be best when considering candidates for TIPS placement.
Project description:BACKGROUND:Patients with acute-on-chronic liver failure (ACLF) precipitated by hepatic injury and extrahepatic insults had distinct clinical phenotypes, and prognosis. This study aimed to validate prognostic models for ACLF and to explore their discriminative abilities in ACLF population categorized by the etiologies of precipitating events. METHODS:This study collected data from 343 consecutive cirrhotic patients hospitalized with the diagnosis of ACLF according to the EASL-CLIF-Consortium definition. The discrimination abilities of prognostic models at the onset of ACLF were tested with the concordance index and area under the receiver operating characteristic curve. RESULTS:Among the entire cohort, 103 patients survived with medical management, nine patients were transplanted, and 231 patients died without liver transplantation. The predictive accuracy of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) for 28-day mortality was similar to the CLIF Consortium Organ Failure (CLIF-C OF) but significantly higher than the CLIF Consortium ACLF, the Child-Turcotte-Pugh, the model for end-stage liver disease (MELD), the MELD-sodium, the integrated MELD, and the Acute Physiology and Chronic Health Evaluation II. Of note, 44 patients had acute hepatic insult triggering ACLF (hepatic-ACLF), 244 were exclusively precipitated by bacterial infection or gastrointestinal bleeding (extrahepatic-ACLF), and 55 cases had no any identifiable potential precipitating events. Patients with hepatic-ACLF had significantly higher 28-day mortality than extrahepatic-ACLF patients. The CLIF-SOFA and CLIF-C OF displayed the highest accuracy significantly outperforming other scoring systems in predicting mortality among patients with hepatic-ACLF and those with extrahepatic-ACLF. CONCLUSION:The CLIF-SOFA and simpler CLIF-C OF are reliable measures of mortality risk in ACLF patients precipitated by either hepatic or extrahepatic insults. Both validated models could be used to stratify the risk of death and improve management of ACLF.
Project description:Our previous study demonstrated that Th17 cells increased significantly in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). However, their prognostic role in HBV-ACLF patients remains unknown.Sixty-eight consecutive HBV-ACLF patients were enrolled in this cohort study. Th17 cells were examined using flow cytometry. Disease severity scores were assessed. ROC curves were used to evaluate the value in predicting prognosis. Survival was analyzed using Kaplan-Meier curves. Predictors of mortality were determined by regression analysis.Th17 cells were significantly higher in HBV-ACLF patients compared to patients with chronic hepatitis B and normal controls (both P?<?.001). Also, Th17 cells were higher in nonsurviving HBV-ACLF patients than in surviving patients (P?=?.014). Th17 cells were positively correlated with CLIF-Consortium ACLF (CLIF-C ACLF) score (r?=?0.240, P?=?.048). ROC curves showed that the frequency of Th17 cells had accuracy in predicting 90-day prognosis equivalent to MELD, MELD-Na and CLIF-C ACLF scores in HBV-ACLF (P?=?.34, P?=?.26, and P?=?.15, respectively). More importantly, the area under the ROC curve (AUROC) increased when Th17 cells were combined with MELD, MELD-Na or CLIF-C ACLF score than using Th17 cells alone (P?=?.021, P?=?.006, and P?=?.023, respectively). Kaplan-Meier analysis revealed that higher Th17 cells (?5.9%) were closely associated with poor overall survival in HBV-ACLF (P?=?.0086). Additionally, multivariate regression analysis showed that the frequency of Th17 cells over 5.9% was an independent predictor of mortality (OR?=?0.154, P?=?.025).Circulating Th17 cells positively correlated with disease severity in HBV-ACLF. The frequency of Th17 cells over 5.9% could serve as a prognostic biomarker for HBV-ACLF patients.
Project description:BACKGROUND/AIMS:This study examined the risk factors associated with mortality in cirrhotic patients hospitalized with variceal bleeding, and evaluated the effects of acute-on-chronic liver failure (ACLF) on the prognosis of these patients. METHODS:This study was retrospectively conducted on patients registered in the Korean acute-on-chronic liver failure study cohort, and on 474 consecutive cirrhotic patients hospitalized with variceal bleeding from January 2013 to December 2013 at 21 university hospitals. ACLF was defined as described by the European Association for the Study of Liver-Chronic Liver Failure Consortium. RESULTS:Among a total of 474 patients, 61 patients were diagnosed with ACLF. The cumulative overall survival (OS) rate was lower in the patients with ACLF than in those without (P<0.001), and patients with higher ACLF grades had a lower OS rate (P<0.001). The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score was identified as a significant prognostic factor in patients hospitalized with variceal bleeding (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.30-1.50; P<0.001), even in ACLF patients with variceal bleeding (HR, 1.32; 95% CI, 1.19-1.46, P<0.001). Concerning the prediction of the mortality risk at 28- and 90-day using CLIF-SOFA scores, c-statistics were 0.895 (95% CI, 0.829-0.962) and 0.897 (95% CI, 0.842-0.951), respectively, and the optimal cut-off values were 6.5 and 6.5, respectively. CONCLUSION:In cirrhotic patients hospitalized with variceal bleeding, the prognosis was poor when accompanied by ACLF, especially depending upon CLIF-SOFA score. CLIF-SOFA model well predicted the 28-day or 90-day mortality for cirrhotic patients who experienced variceal bleeding.
Project description:The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were 'hepatic' and 'coagulation'. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p?<?0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles.
Project description:<label>BACKGROUND</label>Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failure, and high short-term mortality rates. Hemodynamic dysfunction and activation of endogenous vasoconstrictor systems are thought to contribute to the pathogenesis of ACLF. We explored whether copeptin, a surrogate marker of arginine vasopressin, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients.<label>METHODS</label>All 779 patients hospitalized for AD of cirrhosis from the CANONIC database with at least one serum sample available for copeptin measurement were included. Presence of ACLF was defined according to the CLIF-consortium organ failure (CLIF-C OF) score. Serum copeptin was measured in samples collected at days 0-2, 3-7, 8-14, 15-21, and 22-28 when available. Competing-risk regression analysis was applied to evaluate the impact of serum copeptin and laboratory and clinical data on short-term survival.<label>RESULTS</label>Serum copeptin concentration was found to be significantly higher in patients with ACLF compared with those without ACLF at days 0-2 (33 (14-64) vs. 11 (4-26) pmol/L; p?<?0.001). Serum copeptin at admission was shown to be a predictor of mortality independently of MELD and CLIF-C OF scores. Moreover, baseline serum copeptin was found to be predictive of ACLF development within 28 days of follow-up.<label>CONCLUSIONS</label>ACLF is associated with significantly higher serum copeptin concentrations at hospital admission compared with those with traditional AD. Copeptin is independently associated with short-term survival and ACLF development in patients admitted for AD or ACLF.
Project description:Background:Acute-on-chronic liver failure (ACLF), which is characterized by rapid deterioration of liver function and multiorgan failure, has high mortality. This study was designed to identify prognostic scores to predict short-term and long-term outcome in patients with ACLF to facilitate early treatment and thereby improve patient survival. Materials and Methods:We retrospectively analyzed 102 ACLF patients who were hospitalized in the gastroenterology department. The EASL-CLIF criteria were used to define the ACLF. The demographic characteristics and biochemical examination results of the patients were acquired, and seven scores (CTP score, MELD score, MELD-Na, CLIF ACLF score, CLIF-C OF score, and CLIF SOFA score) were calculated 24 h after admission. All patients were observed until loss to follow-up, death, or specific follow-up times (28 days, 3 months, and 6 months), which were calculated after the initial hospital admission. The receiver operating characteristic (ROC) curve was employed to estimate the power of six scores to forecast ACLF patients' outcome. Results:All scores were distinctly higher in nonsurviving patients than in surviving patients and had predictive value for outcome in patients with ACLF at all time points (P < 0.050). The areas under the ROC curve (AUROCs) of the CLIF-SOFA score were higher than those of other scores at all time points. The comparison of the AUROC of the CLIF-SOFA score with other scores was statistically significant at 28 days (P < 0.050), which was the only time point at which it was greater than 0.800. Conclusion:Patients with ACLF have high mortality. These six scores are effective tools for assessing the prognosis of ACLF patients. The CLIF-SOFA score is especially effective for evaluating 28-day mortality.
Project description:BACKGROUND:Despite advancements in pharmacological and device-based treatment, heart failure (HF) continues to impose an enormous burden for health care system worldwide. Decompensation of HF is one of the main causes of hospitalization, therefore the identification of patients with the highest risk of such complication is still of great clinical importance. The prognostic significance and utility of global longitudinal strain (GLS) has been previously studied in patients with the broad spectrum of cardiovascular diseases in various endpoints, however its role in assessing the risk of hospitalization due to HF exacerbation of optimally treated outpatients has not been fully explored. Therefore, the aim of the study was to verify whether the GLS of the left ventricle (LV) derived by 2D speckle tracking echocardiography has, independently of other well-known clinical parameters, an additional impact on the risk of HF decompensation in stable patients with LV systolic dysfunction of ischemic origin. METHODS:In 193 clinically stable HF outpatients with LV ejection fraction (LVEF) ? 50%, GLS, additionally to other clinical parameters, was analyzed. During 34 (14-71) months of follow-up, 58 patients were hospitalized due to HF decompensation (EVENT). RESULTS:EVENT was significantly associated with age, QRS width, NYHA functional class, left atrium diameter, LV systolic and diastolic volume, LVEF, hemoglobin, brain natriuretic peptide, diuretic treatment, absence of beta-blockers, impaired renal function and history of diabetes in univariate Cox analyzes. GLS with pre-specified cut-off value of -9.4% was also significantly associated with the EVENT (HR 15.16; 95% CI 1.81-126.91). After adjusting for above-mentioned parameters GLS was still a significant predictor of hospitalization due to HF decompensation. CONCLUSIONS:GLS measurement can provide incremental information on the risk of HF decompensation in stable outpatients with LV systolic dysfunction of ischemic origin.
Project description:BACKGROUND:Acute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis and is defined by organ failure and high rates of short-term mortality. Patients with ACLF are managed with multiorgan support in the intensive care unit (ICU). Currently, it is unclear when this supportive care becomes futile, particularly in patients who are not candidates for liver transplant. The aim of this study was to determine whether the currently available prognostic scores can identify patients with ACLF in whom prolonged ICU care is likely to be futile despite maximal treatment efforts. METHODS:Data of 202 consecutive patients with ACLF admitted to the ICU at the Royal Free Hospital London between 2005 and 2012 were retrospectively analyzed. Prognostic scores for chronic liver diseases, such as Child-Pugh, Model for End-Stage Liver Disease (MELD), European Foundation for the study of chronic liver failure (CLIF-C) organ failure (OF), and CLIF-C ACLF, were calculated 48 hours after ICU admission and correlated with patient outcome after 28 days. RESULTS:The CLIF-C ACLF score, compared with all other scores, most accurately predicted 28-day mortality, with an area under the receiver operator characteristic of 0.8 (CLIF-C OF, 0.75; MELD, 0.68; Child-Pugh, 0.66). A CLIF-C ACLF score cutoff ??70 identified patients with a 100% mortality within 28 days. These patients had elevated inflammatory parameters representing a systemic inflammatory response, most often renal failure, compared with patients below this cutoff. CONCLUSIONS:Patients with ACLF and high CLIF-C ACLF score (??70) after 48 hours of intensive care may reach a threshold of futility for further ongoing intensive support. The best treatment options in this scenario remain to be determined but may include palliative care.