scholarly journals Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure

Hepatology ◽  
2016 ◽  
Vol 64 (4) ◽  
pp. 1249-1264 ◽  
Author(s):  
Joan Clària ◽  
Rudolf E. Stauber ◽  
Minneke J. Coenraad ◽  
Richard Moreau ◽  
Rajiv Jalan ◽  
...  
Keyword(s):  
Liver Failure ◽  
Systemic Inflammation ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure

Leveraging omics to understand the molecular basis of acute-on-chronic liver failure

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Joan Clària
Keyword(s):  
Liver Failure ◽  
Organ Failure ◽  
Systemic Inflammation ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Short Term Mortality ◽  
Novel Biomarkers ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Abstract Acute-on-chronic liver failure (ACLF) is a complex syndrome that develops in patients with acutely decompensated cirrhosis. In this condition, dysbalanced immune function and excessive systemic inflammation are closely associated with organ failure and high short-term mortality. In this review, we describe how omic technologies have contributed to the characterization of the hyperinflammatory state in patients with acutely decompensated cirrhosis developing ACLF, with special emphasis on the role of metabolomics, lipidomics and transcriptomics in profiling the triggers (pathogen- and damage-associated molecular patterns [PAMPs and DAMPs]) and effector molecules (cytokines, chemokines, growth factors and bioactive lipid mediators) that lead to activation of the innate immune system. This review also describes how omic approaches can be invaluable tools to accelerate the identification of novel biomarkers that could guide the implementation of novel therapies/interventions aimed at protecting these patients from excessive systemic inflammation and organ failure.

The Prediction of in‐Hospital Mortality in Decompensated Cirrhosis with Acute‐on‐Chronic Liver Failure

2021 ◽  
Author(s):  
Florence Wong ◽  
K Rajender Reddy ◽  
Puneeta Tandon ◽  
Jennifer C Lai ◽  
Nishita Jagarlamudi ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Liver Failure ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure

scholarly journals Inhibition of glutamine synthetase in monocytes from patients with acute-on-chronic liver failure resuscitates their antibacterial and inflammatory capacity

Gut ◽  
2018 ◽  
Vol 68 (10) ◽  
pp. 1872-1883 ◽  
Author(s):  
Hannelie Korf ◽  
Johannie du Plessis ◽  
Jos van Pelt ◽  
Sofie De Groote ◽  
David Cassiman ◽  
...  
Keyword(s):  
Glutamine Synthetase ◽  
Liver Failure ◽  
Bacterial Infections ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Phenotypic Characterisation ◽  
Severity Scores ◽  
Aclf Patient

ObjectiveAcute-on-chronic liver failure (ACLF) is associated with dysfunctional circulating monocytes whereby patients become highly susceptible to bacterial infections. Here, we identify the pathways underlying monocyte dysfunction in ACLF and we investigate whether metabolic rewiring reinstates their phagocytic and inflammatory capacity.DesignFollowing phenotypic characterisation, we performed RNA sequencing on CD14+CD16− monocytes from patients with ACLF and decompensated alcoholic cirrhosis. Additionally, an in vitro model mimicking ACLF patient-derived features was implemented to investigate the efficacy of metabolic regulators on monocyte function.ResultsMonocytes from patients with ACLF featured elevated frequencies of interleukin (IL)-10-producing cells, reduced human leucocyte antigen DR isotype (HLA-DR) expression and impaired phagocytic and oxidative burst capacity. Transcriptional profiling of isolated CD14+CD16− monocytes in ACLF revealed upregulation of an array of immunosuppressive parameters and compromised antibacterial and antigen presentation machinery. In contrast, monocytes in decompensated cirrhosis showed intact capacity to respond to inflammatory triggers. Culturing healthy monocytes in ACLF plasma mimicked the immunosuppressive characteristics observed in patients, inducing a blunted phagocytic response and metabolic program associated with a tolerant state. Metabolic rewiring of the cells using a pharmacological inhibitor of glutamine synthetase, partially restored the phagocytic and inflammatory capacity of in vitro generated- as well as ACLF patient-derived monocytes. Highlighting its biological relevance, the glutamine synthetase/glutaminase ratio of ACLF patient-derived monocytes positively correlated with disease severity scores.ConclusionIn ACLF, monocytes feature a distinct transcriptional profile, polarised towards an immunotolerant state and altered metabolism. We demonstrated that metabolic rewiring of ACLF monocytes partially revives their function, opening up new options for therapeutic targeting in these patients.

scholarly journals Septic shock after liver transplantation successfully treated with endotoxin and cytokine adsorption continuous renal replacement therapy: a case report and literature review

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052094043
Author(s):  
Yining Li ◽  
Linshan Zhou ◽  
Lingzhi Yang ◽  
Fang Yuan
Keyword(s):  
Septic Shock ◽  
Liver Transplantation ◽  
Renal Replacement Therapy ◽  
Liver Failure ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Chronic Liver ◽  
Inflammatory Factors ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure

Endotoxins and cytokines play an important role in multiple organ failure pathogenesis in patients with severe Gram-negative bacterial infection. We present a clinical case where an oXiris hemofilter was used for continuous renal replacement therapy (CRRT) treatment in a patient with septic shock after liver transplantation. A 35-year-old man with a 20-year history of hepatitis B presented with jaundice, loss of appetite, and decreased urine output. He was diagnosed with decompensated cirrhosis with acute-on-chronic liver failure, and liver transplantation was indicated. The day after surgery, he developed hyperthermia, hypotension, anuria, and a progressive increase in blood inflammatory markers and creatinine. Combined with the donor source and blood culture results, septic shock after transplantation was considered. The patient was immediately treated with endotoxin and cytokine adsorption CRRT (oXiris hemofilter) with tigecycline, caspofungin, and ganciclovir as anti-infectives. After 48 hours on CRRT, his blood pressure gradually stabilized, the CLIF Consortium Acute-on-Chronic Liver Failure score decreased from 63 to 43. Procalcitonin, endotoxin, and the inflammatory factors interleukin (IL)-6 and IL-10 also decreased gradually. The patient’s liver and kidney functions were completely restored. Our experience suggests that oXiris CRRT combined with antibacterial therapy is an effective treatment for septic shock after liver transplantation.

Coagulation Failure in Patients With Acute-on-Chronic Liver Failure and Decompensated Cirrhosis: Beyond the International Normalized Ratio

Hepatology ◽  
2018 ◽  
Vol 68 (6) ◽  
pp. 2325-2337 ◽  
Author(s):  
Annabel Blasi ◽  
Andrea Calvo ◽  
Verónica Prado ◽  
Enric Reverter ◽  
Juan Carlos Reverter ◽  
...  
Keyword(s):  
Liver Failure ◽  
International Normalized Ratio ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure
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