Role of Infections in Acute-on-Chronic Liver Failure

2015 ◽  
Vol 33 (4) ◽  
pp. 577-581 ◽  
Author(s):  
Richard Moreau
Keyword(s):  
Liver Failure ◽  
Immune Suppression ◽  
Bacterial Infections ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Prolonged Stay ◽  
Major Mechanism ◽  
Risk Of Death ◽  
Increased Risk ◽  
Organ Failures

Patients with cirrhosis are prone to developing bacterial infections. Moreover, bacterial infection is the most common identifiable trigger of acute-on-chronic liver failure (ACLF), which is characterized by organ failures and a high risk of death. There is evidence of an excessive immune response of the host as a major mechanism leading to the development of organ failures in patients with cirrhosis. However, a role for direct tissue damage caused by bacterial toxins and virulence factors cannot be excluded. Failed tolerance mechanisms may also contribute to organ failures, although the involved mechanisms are unclear. A proportion of patients with infection-related ACLF have a prolonged stay in the intensive care unit. These patients have immune suppression, increased risk of superinfection and poor outcome. Immune suppression might be a consequence of the first infection episode that has led patients to be admitted to hospital.

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.

Acute-on-chronic liver failure: to admit to intensive care or not?

2020 ◽  
Vol 81 (9) ◽  
pp. 1-6
Author(s):  
Asif Arshad ◽  
Lylah Irshad ◽  
Theodore Nabavi ◽  
Tony Whitehouse
Keyword(s):  
Liver Failure ◽  
Organ Failure ◽  
Gastrointestinal Haemorrhage ◽  
Chronic Liver ◽  
Organ Support ◽  
Chronic Liver Failure ◽  
Short Term Mortality ◽  
Organ Failures ◽  
Clinical Scoring ◽  
Excessive Alcohol

Acute-on-chronic liver failure is used to describe an acute decline in liver function in a patient with existing liver disease combined with other organ failure. Acute-on-chronic liver failure is associated with high short-term mortality, and the greater the number and severity of organ failures, the higher the mortality. The most commonly identified precipitants of acute-on-chronic liver failure include bacterial infection, gastrointestinal haemorrhage, viral hepatitis and recent excessive alcohol intake. Since some of these aetiologies are treatable, organ failure may return to pre-decompensation levels in up to 55% of patients. As a result, a trial of critical care treatment may be appropriate for many of these patients. Clinical scoring tools may help clinicians recognise futility, allowing timely withdrawal of organ support and shifting the focus of care toward palliation.

scholarly journals Applicability of the Chronic Liver Failure-Consortium score in patients with cirrhosis and bacterial infections: a single-clinic experience

2021 ◽  
Vol 55 (4) ◽  
pp. 239-245
Author(s):  
D.I. Haurylenka ◽  
N.N. Silivontchik
Keyword(s):  
Liver Failure ◽  
Bacterial Infections ◽  
Serum Bilirubin Level ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Acute Decompensation ◽  
Clinic Experience ◽  
Cirrhotic Patients ◽  
The City ◽  
Number Needed To Harm

Background. The frequency and characteristics of acute-on-chronic liver failure (ACLF) are reported in numerous articles from different countries. The aim of the study was to assess the cirrhosis decompensation in patients with bacterial infections based on the Chronic Liver Failure-Consortium (CLIF-C) score in one of the city clinics in Belarus. Materials and methods. The patients underwent laboratory and instrumental studies during the hospitalization. The assessment of the syndrome of acute-on-chronic liver failure was performed using the CLIF-C score. Bacterial infections were diagnosed on the basis of standard criteria. Results. The study included 151 cirrhotic patients, 87 males and 64 females. Median age was 55 years (Q1 = 43; Q3 = 61). Cirrhosis was predominantly due to alcohol addiction — 83 patients (55 %). ACLF was diagnosed in 44 of 151 patients with cirrhosis (29.1 %; 95% confidence interval (CI) 22.0–37.1). Bacterial infections were detected in 67 people (44.4 %; 95% CI 36.3–52.7). Most often patients had liver failure that was detected by an increase in serum bilirubin level. Among individuals with upper gastrointestinal bleedings, number needed to harm for developing ACLF was 3.3 (95% CI 2.2–4.4). The risk of developing ACLF grade 2 and 3 in cirrhotic patients with infections was 8.2, with 95% CI 1.0–69.6 (number needed to harm was 12.9; 95% CI 10.7–15.0). Bacterial infections increase the risk of acute decompensation in patients with cirrhosis (odds ratio = 2.0, p = 0.048). Conclusions. The CLIF-C score is quite applicable in our cohort of patients with cirrhosis.

scholarly journals Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures

Hepatology ◽  
2014 ◽  
Vol 60 (1) ◽  
pp. 250-256 ◽  
Author(s):  
Jasmohan S. Bajaj ◽  
Jacqueline G. O'Leary ◽  
K. Rajender Reddy ◽  
Florence Wong ◽  
Scott W. Biggins ◽  
...  
Keyword(s):  
Liver Failure ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Organ Failures

scholarly journals Multidrug-resistant bacterial infections in patients with decompensated cirrhosis and with acute-on-chronic liver failure in Europe

2019 ◽  
Vol 70 (3) ◽  
pp. 398-411 ◽  
Author(s):  
Javier Fernández ◽  
Verónica Prado ◽  
Jonel Trebicka ◽  
Alex Amoros ◽  
Thierry Gustot ◽  
...  
Keyword(s):  
Liver Failure ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure
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