A new model for identification of HBV-related pre-ACLF.
Ontology highlight
ABSTRACT:
SUBMITTER: Jalan R
PROVIDER: S-EPMC9472060 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Publications
A new model for identification of HBV-related pre-ACLF.
Jalan Rajiv R Sundaram Vinay V
JHEP reports : innovation in hepatology 20220817 10
Similar Datasets
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.
| S-EPMC3673980 | biostudies-literature
Project description:BackgroundEarly identification of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) holds crucial importance in guiding clinical management and reducing mortality. However, existing scoring systems often overlook patient's underlying clinical condition, which significantly impacts prognosis.AimsUse the age-adjusted Charlson comorbidity index (aCCI) to evaluate the patient's complications to develop a more precise model for predicting transplant-free mortality in HBV-ACLF patients.MethodsNine hundred and six patients were included for investigation and were segregated into a training cohort and a temporal validation cohort according to the chronological order of admission in a ratio of 7:3. In the training cohort, univariate analysis, logistic regression analysis and LASSO regression analysis were used to construct a prognostic model and it was subsequently validated in a temporal validation cohort and an external validation cohort.ResultsWe found total bilirubin, neutrophils, international normalised ratio and aCCI exhibited significant associations with 28-day transplant-free mortality and established a novel prognostic model, named aCCI-HBV-ACLF. The model demonstrated strong predictive performance, with area under the receiver operating characteristic curve (ROC) values of 0.859 for 28-day mortality, 0.822 for 90-day mortality. In the temporal validation cohort, aCCI-HBV-ACLF achieved area under the ROC values of 0.869 for 28-day mortality and 0.850 for 90-day mortality. In the external validation cohort, aCCI-HBV-ACLF had area under the ROC values of 0.868 for 28-day mortality and 0.888 for 90-day mortality.ConclusionsThis study proposes a new prognostic model, which achieved excellent predictive ability for 28-/90-day transplant-free mortality rates among patients with HBV-ACLF.
| S-EPMC11671711 | biostudies-literature
Project description:Background and aims: Acute-on-chronic liver failure (ACLF) is an acute liver and multisystem failure in patients with previously stable cirrhosis. A common cause of ACLF is sepsis secondary to bacterial infection. Sepsis-associated ACLF involves a loss of differentiated liver function in the absence of direct liver injury, and its mechanism is unknown. We aimed to study the mechanism of sepsis associated ACLF using a novel mouse model. Approach and Results: Sepsis-associated ACLF was induced by cecal ligation and puncture procedure (CLP) in mice treated with thioacetamide (TAA). The combination of TAA and CLP resulted in a significant decrease in liver synthetic function and high mortality. These changes were associated with reduced metabolic gene expression and increased C/EBPβ transcriptional activity. We found that C/EBPβ binding to its target gene promoters was increased. In humans C/EBPβ chromatin binding was similarly increased in ACLF group compared to control cirrhosis. Hepatocyte specific Cebpb knockout mice had reduced mortality and increased gene expression of hepatocyte differentiation markers in TAA/CLP mice, suggesting that C/EBPβ promotes liver failure in these mice. C/EBPβ activation was associated with endothelial dysfunction, characterized by reduced Angiopoietin-1/Angiopoietin-2 ratio and increased endothelial production of HGF. Angiopoietin-1 supplementation or Hgf knockdown reduced hepatocyte C/EBPβ accumulation, restored liver function, and reduced mortality, suggesting that endothelial dysfunction induced by sepsis drives acute-on-chronic liver failure via HGF-C/EBPβ pathway. Conclusion: The transcription factor C/EBPβ is activated in both mouse and human ACLF and is a potential therapeutic target to prevent liver failure in patients with sepsis and cirrhosis.
2023-04-04 | GSE228610 | GEO
Project description:Background/aimTo investigate the prognostic value of circulating apolipoprotein AI (apoAI) levels and develop a new prognostic model in individuals with acute-on-chronic liver failure (ACLF) and acute decompensation (AD) of liver cirrhosis caused by hepatitis B virus (HBV) infection.MethodsBaseline levels of serum lipids were measured, and data concerning the presence of complications were collected from 561 HBV-ACLF and AD patients. Survival analysis was conducted by log-rank test. Proportional hazards model was used to perform multivariate analysis. The dynamics of serum apoAI levels were also explored in 37 HBV-ACLF patients.ResultsIn the cohort, the negatively correlation was found between the Model for End-Stage Liver Disease (MELD) score and serum apoAI levels (r = -0.7946, P < 0.001). Circulating apoAI concentration was an independent risk factor for 90-day survival according to Cox multivariate analysis. A new prognostic score-integrated serum lipid profile for ACLF patients (Lip-ACLF score = 0.86×International Normalized Ratio (INR) + 0.0034×total bilirubin (TBIL) (µmol/L) + 0.99× hepatorenal syndrome (HRS) (HRS: no/1; with/2) + 0.50×hepatic encephalopathy (HE) (grade/ponint: no/1; 1-2/2; 3-4/3) - 2.97×apoAI (g/L) + 5.2) was subsequently designed for the derivation cohort. Compared to MELD score, Child-Turcotte-Pugh (CTP) score or apoAI, Lip-ACLFs was superior for the prediction of 90-day outcomes (receiver operating characteristic curve (ROC): 0.930 vs. 0.885, 0.833 or 0.856, all P < 0.01), as was the validation cohort (ROC 0.906 vs. 0.839, 0.857 or 0.837, all P < 0.05). In Kaplan‒Meier survival analysis, low apoAI levels (< 0.42 g/L) at baseline indicated poor prognosis in ACLF and AD patients. Among the 37 patients, the deceased individuals were characterised with significantly decreased serum apoAI levels during the follow-up test compared with those at baseline (P < 0.05), whereas in patients with a good prognosis, the serum apoAI levels remained stable during the follow-up.ConclusionIn HBV-ACLF and AD patients, lower serum apoAI levels suggest greater disease severity and 90-day mortality risk. For predicting the short-term prognosis of these patients, the new Lip-ACLF score might serve as a potential model.
| S-EPMC11789380 | biostudies-literature
Project description:Sepsis related ACLF mouse model
| PRJNA950440 | ENA
Project description:BackgroundHepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening disease with a high mortality rate; the systemic inflammatory response plays a vital role in disease progression. We aimed to determine if a miRNA-mRNA co-regulatory network exists in the peripheral blood mononuclear cells (PBMCs) of HBV-ACLF patients, which might be important for prognosis.MethodsIn patients with HBV-ACLF meeting COSSH-ACLF criteria, age, liver cirrhosis and INR were independent risk factors for 28-day and 90-day poor prognosis. COSSH-ACLFs was a superior prognostic model. mir-6840-3p-JADE2 may promote the progression of ACLF and lead to poor prognosis. Meanwhile, mir-6840-3p and mir-6861-3p can be used as markers of short-term poor prognosis. Finally, ALSS treatment is not only the blood material exchange of patients, but also changes part of the immune state of patients. Among them, cytokine cytokine receptor interaction may play an important role in determining the therapeutic effect.MethodsTranscriptome-wide microRNA (miRNA) and mRNA microarrays were used to define the miRNA and mRNA expression profiles of the PBMCs of HBV-ACLF patients in a discovery cohort. The targets of the miRNAs were predicted. We built a miRNA-mRNA regulatory network through bioinformatics analysis, and used quantitative real-time polymerase chain reaction (qRT-PCR) to assess the importance of candidate miRNAs and mRNAs. We also assessed the direct and transcriptional regulatory effects of miRNAs on target mRNAs using a dual-luciferase reporter assay.ResultsThe miRNA/mRNA PBMC expression profiles of the discovery cohort, of whom eight survived and eight died, revealed a prognostic interactive network involving 38 miRNAs and 313 mRNAs; this was constructed by identifying the target genes of the miRNAs. We validated the expression data in another cohort, of whom 43 survived and 35 died; miR-6840-3p, miR-6861-3p, JADE2, and NR3C2 were of particular interest. The levels of miR-6840-3p and miR-6861-3p were significantly increased in the PBMCs of the patients who died, and thus predicted prognosis (areas under the curve values = 0.665 and 0.700, respectively). The dual-luciferase reporter assay indicated that miR-6840-3p directly targeted JADE2.ConclusionWe identified a prognostic miRNA-mRNA co-regulatory network in the PBMCs of HBV-ACLF patients. miR-6840-3p-JADE2 is a potential miRNA-mRNA pair contributing to a poor prognosis.
| S-EPMC8113841 | biostudies-literature
Project description:Early prognostic assessment of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important for guiding clinical management and reducing mortality. The aim of this study was to dynamically monitor the clinical characteristics of HBV-ACLF patients, thereby allowing the construction of a novel prognostic scoring model to predict the outcome of HBV-ACLF patients. Clinical data was prospectively collected for 518 patients with HBV-ACLF and randomly divided into training and validation sets. We constructed day-1, day-2, and day-(1 + 3) prognostic score models based on dynamic time points. The prognostic risk score constructed for day-3 was found to have the best predictive ability. The factors included in this scoring system, referred to as DSM-ACLF-D3, were age, hepatic encephalopathy, alkaline phosphatase, total bilirubin, triglycerides, very low-density lipoprotein, blood glucose, neutrophil count, fibrin, and INR. ROC analysis revealed the area under the curve predicted by DSM-ACLF-D3 for 28-day and 90-day mortality (0.901 and 0.889, respectively) was significantly better than those of five other scoring systems: COSSH-ACLF IIs (0.882 and 0.836), COSSH-ACLFs (0.863 and 0.832), CLIF-C ACLF (0.838 and 0.766), MELD (0.782 and 0.762) and MELD-Na (0.756 and 0.731). Dynamic monitoring of the changes in clinical factors can therefore significantly improve the accuracy of scoring models. Evaluation of the probability density function and risk stratification by DSM-ACLF-D3 also resulted in the best predictive values for mortality. The novel DSM-ACLF-D3 prognostic scoring model based on dynamic data can improve early warning, prediction and clinical management of HBV-ACLF patients.
| S-EPMC11219721 | biostudies-literature
Project description:The transcriptomic profiles of circulating neutrophils were compared between patients with ACLF (N=10), patients with CLC (N=10) and HC (N=10). Compared with CLC-neutrophils, the expression of 1022 genes were found to be upregulated in ACLF-neutrophils, and 1101 genes were downregulated. And compared to HC, the expression of 726 genes were up-regulated in ACLF-neutrophils, and 711 genes were down-regulated. The pathway analysis identified mutiple pathways enriched or down-regulated in ACLF-neutrophils when comparing with neutrophils from CLC or HC groups.
2024-02-25 | GSE165024 | GEO
Project description:We aimed to develop a prediction model based on the PIRO concept (Predisposition, Injury, Response and Organ failure) for patients with Hepatitis B Virus (HBV) related acute-on-chronic liver failure (ACLF). 774 patients with HBV related ACLF defined in the CANONIC study were analyzed according to PIRO components. Variables associated with mortality were selected into the prediction model. Based on the regression coefficients, a score for each PIRO component was developed, and a classification and regression tree was used to stratify patients into different nodes. The prediction model was then validated using an independent cohort (n = 155). Factors significantly associated with 90-day mortality were: P: age, gender and ACLF type; I: drug, infection, surgery, and variceal bleeding; R: systemic inflammatory response syndrome (SIRS), spontaneous bacteria peritonitis (SBP), and pneumonia; and O: the CLIF consortium organ failure score (CLIF-C OFs). The areas under the receiver operating characteristics curve (95% confidence interval) for the combined PIRO model for 90-day mortality were 0.77 (0.73-0.80). Based on the scores for each of the PIRO components and the cut-offs estimated from the classification and regression tree, patients were stratified into different nodes with different estimated death probability. Based on the PIRO concept, a new prediction model was developed for patients with HBV related ACLF, allowing stratification into different clusters using the different scores obtained in each PIRO component. The proposed model will likely help to stratify patients at different risk, defining individual management plans, assessing criteria for specific therapies, and predicting outcomes.
| S-EPMC7677318 | biostudies-literature
Project description:ObjectiveHepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics.MethodsFour hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs).ResultsThe functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis.ConclusionsThis study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.
| S-EPMC8666828 | biostudies-literature