Faculty Opinions recommendation of Incidence and Mortality of Acute on Chronic Liver Failure using Two Definitions in Patients with Compensated Cirrhosis.

ObjectiveSystemic inflammation predisposes acutely decompensated (AD) cirrhosis to the development of acute-on-chronic liver failure (ACLF). Supportive treatment can improve AD patients, becoming recompensated. Little is known about the outcome of patients recompensated after AD. We hypothesise that different inflammasome activation is involved in ACLF development in compensated and recompensated patients.Design249 patients with cirrhosis, divided into compensated and recompensated (previous AD), were followed prospectively for fatal ACLF development. Two external cohorts (n=327) (recompensation, AD and ACLF) were included. Inflammasome-driving interleukins (ILs), IL-1α (caspase-4/11-dependent) and IL-1β (caspase-1-dependent), were measured. In rats, bile duct ligation-induced cirrhosis and lipopolysaccharide exposition were used to induce AD and subsequent recompensation. IL-1α and IL-1β levels and upstream/downstream gene expression were measured.ResultsPatients developing ACLF showed higher baseline levels of ILs. Recompensated patients and patients with detectable ILs had higher rates of ACLF development than compensated patients. Baseline CLIF-C (European Foundation for the study of chronic liver failure consortium) AD, albumin and IL-1α were independent predictors of ACLF development in compensated and CLIF-C AD and IL-1β in recompensated patients. Compensated rats showed higher IL-1α gene expression and recompensated rats higher IL-1β levels with higher hepatic gene expression. Higher IL-1β detection rates in recompensated patients developing ACLF and higher IL-1α and IL-1β detection rates in patients with ACLF were confirmed in the two external cohorts.ConclusionPrevious AD is an important risk factor for fatal ACLF development and possibly linked with inflammasome activation. Animal models confirmed the results showing a link between ACLF development and IL-1α in compensated cirrhosis and IL-1β in recompensated cirrhosis.

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A195 SURIVIVAL IN ACUTE ON CHRONIC LIVER FAILURE IN COMPENSATED CIRRHOSIS VS DECOMPENSATED CIRRHOSIS

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz006.194 ◽

2019 ◽

Vol 2 (Supplement_2) ◽

pp. 383-384

Author(s):

N Zhou ◽

E Kelly

Keyword(s):

Liver Failure ◽

Chronic Liver ◽

Decompensated Cirrhosis ◽

Chronic Liver Failure ◽

Compensated Cirrhosis

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Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure

Hepatology International ◽

10.1007/s12072-021-10266-8 ◽

2021 ◽

Author(s):

Kessarin Thanapirom ◽

Tongluk Teerasarntipan ◽

Sombat Treeprasertsuk ◽

Ashok Choudhury ◽

Manoj K. Sahu ◽

...

Keyword(s):

Liver Disease ◽

Liver Failure ◽

Mortality Rates ◽

Chronic Liver ◽

Hbv Reactivation ◽

Chronic Liver Failure ◽

Alcoholic Fatty Liver ◽

Compensated Cirrhosis ◽

Research Consortium ◽

Clinical Trials Registry

Abstract Background and aims Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. Methods A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. Results Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36–0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43–0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred. Conclusions The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.

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Serum CXCL1 Is a Prognostic Factor for Patients With Hepatitis B Virus–Related Acute-On-Chronic Liver Failure

Frontiers in Medicine ◽

10.3389/fmed.2021.657076 ◽

2021 ◽

Vol 8 ◽

Author(s):

Lanlan Xiao ◽

Shima Tang ◽

Lingjian Zhang ◽

Shanshan Ma ◽

Yalei Zhao ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Liver Failure ◽

Neutrophil Count ◽

Chronic Liver ◽

Healthy Controls ◽

Chronic Liver Failure ◽

Compensated Cirrhosis ◽

B Virus ◽

Chronic Hbv

Purpose: Neutrophils and cytokines play a major role in the pathogenesis of acute-on-chronic liver failure (ACLF). We aimed to determine whether chemokine (CXC) ligand 1 (CXCL1), a key marker of neutrophil recruitment and activation, could predict the severity and prognosis of hepatitis B virus–related ACLF (HBV-ACLF).Methods: Hospitalized patients with HBV-ACLF were enrolled in a prospective study and stratified as survivors (alive at 28 days) and nonsurvivors (deceased at 28 days). Serum CXCL1 levels were measured in healthy controls, patients with chronic HBV, patients with HBV-related compensated cirrhosis, and patients with HBV-ACLF. Univariate and multivariable logistic analyses, Pearson correlation analysis, area under the receiver operating characteristic curve (AUROC), and Z tests were used to evaluate the performance of CXCL1 as a marker in HBV-ACLF.Results: Patients with HBV-ACLF had significantly higher serum levels of CXCL1 and neutrophil count than healthy controls and patients with chronic HBV or HBV-related compensated cirrhosis (P < 0.01, respectively). Among patients with HBV-ACLF, survivors had lower serum CXCL1 levels and neutrophil count than those of nonsurvivors (P < 0.001, P < 0.05, respectively). Serum CXCL1 level was positively correlated with neutrophil count (r = 0.256, P = 0.001), ACLF grade (r = 0.295, P < 0.001) and organ failure, including coagulation (r = 0.21, P = 0.005) and brain failure (r = 0.198, P = 0.008). Multivariable logistic analyses showed serum CXCL1 [OR (95% CI) = 1.017 (1.009–1.025), P < 0.001] was an independent risk factor for 28-day mortality in HBV-ACLF. Meanwhile, the AUROC analysis demonstrated that serum CXCL1 [0.741 (0.669–0.804)] might be a reliable prognostic biomarker for patients with HBV-ACLF.Conclusions: Overall, serum CXCL1 can serve as a biomarker indicating the severity of disease and prognosis for patients with HBV-ACLF. CXCL1 might also be a therapeutic target in this disease.

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Gene profiling of Toll-like receptor signalling pathways in neutrophils of patients with acute-on-chronic liver failure

Journal of Translational Medicine ◽

10.1186/s12967-021-03135-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yi Zhang ◽

Wei Wu ◽

Yijie Wang ◽

Lingjia Tong ◽

Meng Hong ◽

...

Keyword(s):

Liver Failure ◽

Tissue Injury ◽

Fold Change ◽

Chronic Liver ◽

Signalling Pathway ◽

Decompensated Cirrhosis ◽

Signalling Pathways ◽

Chronic Liver Failure ◽

Compensated Cirrhosis ◽

Tlr Signalling

Abstract Objectives Toll-like receptors (TLRs) on neutrophils play a crucial role in detecting pathogens and organ/tissue injury in acute-on-chronic liver failure (ACLF). However, little is known about the exact mechanisms and potential signalling pathways. The aim of this study was to investigate alterations in TLR signalling pathways in neutrophils of ACLF patients. Methods Twenty-seven patients with compensated cirrhosis (n = 9), decompensated cirrhosis (n = 9) and ACLF (n = 9) were enrolled in the study. Neutrophils were isolated, and alterations in TLR signalling pathways were evaluated using an RT2 Profiler™ PCR Array. The fold change for each gene (2(−∆∆CT)) was compared among the groups. Genes with a fold change ratio of ≥ 2 or ≤ 0.5 along with a p value of < 0.05 were considered to be differentially expressed. Results A total of 17 genes were upregulated in neutrophils from patients with compensated cirrhosis and were mainly distributed in adaptors, TLR-interacting proteins and downstream pathways. Six genes were detected in patients with decompensated cirrhosis. A trend of downregulation of genes in the TLR signalling pathway was observed in neutrophils of patients with cirrhosis and ACLF. TLR3, IFNG, IL1B, TBK1, CCL2 and LTA were downregulated in neutrophils. Moreover, CD14 and IL10 were upregulated in neutrophils of ACLF patients. Conclusions TLR signalling pathway genes were differentially regulated in neutrophils between cirrhosis and ACLF. In ACLF patients, defective expression of TLR3 and IFN, along with enhanced CD14 and IL10 expression, was characterized by transcriptional alterations of neutrophils.

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Gene Profiling of Toll-like Receptor Signaling Pathways in Neutrophils of Patients With Acute-on-chronic Liver Failure

10.21203/rs.3.rs-541965/v1 ◽

2021 ◽

Author(s):

Yi Zhang ◽

Wei Wu ◽

Yijie Wang ◽

Lingjia Tong ◽

Meng Hong ◽

...

Keyword(s):

Liver Failure ◽

Signaling Pathways ◽

Signaling Pathway ◽

Tissue Injury ◽

Fold Change ◽

Chronic Liver ◽

Chronic Liver Failure ◽

Tlr Signaling ◽

Compensated Cirrhosis ◽

Tlr Signaling Pathway

Abstract Objectives: Toll-like receptors (TLRs) of neutrophils play a crucial role in detecting pathogens and organ/tissue injury in acute-on-chronic liver failure (ACLF). However, little is known about the exact mechanisms and the potential signaling pathways. The aim of this study was to investigate alterations of TLR signaling pathways in neutrophils of ACLF patients.Methods: Twenty-seven patients with compensated cirrhosis (n=9), de-compensated cirrhosis (n=9) and ACLF (n=9) were enrolled in the study. Neutrophils were isolated, and alterations in TLR signaling pathways were evaluated using an RT² Profiler™ PCR Array. The fold change for each gene (2(-∆∆CT)) was compared among the groups. Genes with a fold change ratio of ≥2 or ≤0.5 along with a p value of < 0.05 were considered to be differentially expressed.Results: A total of 17 genes were up-regulated in neutrophils from patients with compensated cirrhosis, which were mainly distributed in adaptors, TLR-interacting proteins and downstream pathways. Six genes were detected in patients with de-compensated cirrhosis. A trend of down-regulation of genes in the TLR signaling pathway was observed in neutrophils of patients with cirrhosis and ACLF. TLR3, IFNG, IL1B, TBK1, CCL2 and LTA were downregulated in neutrophils. Moreover, CD14 and IL10 were up regulated in neutrophils of ACLF patients.Conclusions: TLR signaling pathway genes were differentially regulated in neutrophils between cirrhosis and ACLF. In ACLF patients, there was defective expression of TLR3 and IFN, along with enhanced CD14 and IL10 expression, characterized by transcriptional alterations of neutrophils.

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