Th17 cells over 5.9% at admission indicate poor prognosis in patients with HBV-related acute-on-chronic liver failure.
ABSTRACT: 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?
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:AIM:To determine the prognostic risk factors of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) treated with plasma exchange (PE)-based artificial liver support system (ALSS), and create a prognostic predictive model. METHODS:A total of 304 HBV-ACLF patients who received PE-based ALSS were retrospectively analyzed. Potential prognostic factors on admission associated with survival were investigated. Of note, 101 additional patients were analyzed to validate the performance of the prognostic models. RESULTS:According to 28-day survival, a total of 207 patients who survived and 97 non-survivors were identified in the derivation group. Overall, 268 (88.2%) ACLF cases were caused by reactivation of HBV. Cox proportional hazards regression model revealed that age, total bilirubin, ln (alpha-fetoprotein [AFP]), encephalopathy (HE) score, sodium level, and international normalized ratio (INR) were independent risk factors of short-term prognosis. We built a model named ALSS-prognosis model (APM) to predict the 28-day survival of HBV-ACLF patients with ALSS; the model APM showed potentially better predictive performance for both the derivation and validation groups than MELD, MELD-Na, and CLIF-C ACLF score. CONCLUSIONS:Low AFP was found to be an independent risk factor for high mortality in HBV-ACLF patients treated with PE-based ALSS. We generated a new model containing AFP, namely APM, which showed potentially better prediction performance than MELD, MELD-Na, and CLIF-C ACLF score for short-term outcomes, and could aid physicians in making optimal therapeutic decisions.
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:IL-17-producing CD8+ T (Tc17) cells promote inflammation and have been identified in chronic hepatitis. However, the role of Tc17 cells in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF) remains unclear. Methods:The frequency of Tc17 cells in blood samples from 66 patients with HBV-ACLF was determined by flow cytometry. The levels of Tc17 cell-related cytokines were measured by FlowCytomix assays. The prognostic prediction accuracy was evaluated by the receiver operating characteristic (ROC) curve analysis. Survival was analyzed using Kaplan-Meier curves. Mortality predictors were determined by the Cox regression analysis. Results:The frequency of Tc17 cells was markedly higher in patients with HBV-ACLF than in those with chronic hepatitis B and normal control subjects. Increased frequencies of Tc17 cells may indicate liver injury and were positively correlated with disease severity. The Tc17 cell frequency was significantly higher in non-surviving patients with HBV-ACLF than in surviving patients. The ROC curve analysis showed that Tc17 cell frequency accurately predicted 90-day survival in patients with HBV-ACLF, with an accuracy equivalent to those of the Model for End-Stage Liver Disease (MELD), MELD-Na, and Chronic Liver Failure Consortium ACLF scores. Kaplan-Meier analysis showed an association between the increase in circulating Tc17 cells and poor overall survival in patients with HBV-ACLF. Moreover, the multivariate Cox regression analysis showed that Tc17 cell frequency was an independent predictor of overall survival in patients with HBV-ACLF. Conclusion:Tc17 cells may play a proinflammatory role in HBV-ACLF pathogenesis. Furthermore, the increased frequency of circulating Tc17 cells could be an independent prognostic biomarker in patients with HBV-ACLF.
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: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:It is challenging to predict the outcome of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) through existing prognostic models. Our aim was to establish a novel dynamic model to improve the predictive efficiency of 30-day mortality in HBV-ACLF patients.305 patients who were diagnosed as HBV-ACLF (derivation cohort, n=211; validation cohort, n=94) were included in this study. The HBV-ACLF dynamic (HBV-ACLFD) model was constructed based on the daily levels of predictive variables in 7 days after diagnosis combined with baseline risk factors by multivariate logistic regression analysis. The HBV-ACLFD model was compared with the Child-Turcotte-Pugh (CTP) score, end-stage liver disease (MELD) score, and MELD within corporation of serum sodium (MELD-Na) score by the area under the receiver-operating characteristic curves (AUROC).The HBV-ACLFD model demonstrated excellent discrimination with AUROC of 0.848 in the derivation cohort and of 0.813 in the validation cohort (p=0.620). The performance of the HBV-ACLFD model appeared to be superior to MELD score, MELD-Na score and CTP score (P<0.0001).The HBV-ACLFD model can accurately predict 30-day mortality in patients with HBV-ACLF, which is helpful to select appropriate clinical procedures, so as to relieve the social and economic burden.
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.
Project description:<h4>Unlabelled</h4>Analysis of the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) is essential to elucidate the pathogenesis of HBV-ACLF and identify HBV-ACLF-specific biomarkers. In this study, high-throughput sequencing was performed to characterize the transcriptome of PMBCs from patients with HBV-ACLF. Specifically, 2381 differentially expressed genes (DEGs) and 776 differentially expressed transcripts were identified through comparisons with patients with chronic hepatitis B (CHB) and healthy controls. Gene Ontology (GO) analysis identified 114 GO terms that were clustered into 12 groups. We merged 10 dysregulated genes selected from these grouped GO terms and non-clustered terms with four significant genes with a specificity of >0.8 in the HBV-ACLF patients to obtain a set of 13 unique genes. The quantitative real-time polymerase chain reaction (qRT-PCR) validation of the top six genes (CYP19A1, SEMA6B, INHBA, DEFT1P, AZU1 and DEFA4) was consistent with the results of messenger ribonucleic acid (mRNA) sequencing. A further receiver operating characteristic (ROC) analysis revealed that the areas under the ROC curves of the six genes were all >0.8, which indicated their significant diagnostic potentials for HBV-ACLF.<h4>Conclusion</h4>The transcriptome characteristics of PBMCs are altered in patients with HBV-ACLF, and six genes may serve as biomarkers of HBV-ACLF.
Project description: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.