Bacterial Infections in Acute-on-Chronic Liver Failure

2018 ◽  
Vol 38 (02) ◽  
pp. 121-133 ◽  
Author(s):  
Lingling Yang ◽  
Tianzhou Wu ◽  
Jiang Li ◽  
Jun Li
Keyword(s):  
Liver Failure ◽  
Bacterial Infections ◽  
Management Strategies ◽  
Clinical Syndrome ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Bacterial Peritonitis ◽  
Specific Complication ◽  
Short Term Mortality ◽  
Tract Infections

AbstractAcute-on-chronic liver failure (ACLF) is a newly recognized clinical syndrome characterized by preexisting chronic liver disease or cirrhosis with organ failure and high 28-day mortality (50–90%). Bacterial infections (BIs) play pivotal roles in the development and progression of ACLF either as a main precipitating event or a specific complication. The main organisms isolated as triggering ACLF are Gram-positive bacteria, followed by Gram-negative bacteria. Spontaneous bacterial peritonitis, pneumonia, urinary tract infections, and skin infections are prevalent infections that trigger and complicate ACLF. Despite appropriate antibiotic treatment, BIs account for poor ACLF outcomes and lead to a worse clinical course and higher intensive care unit admission and short-term mortality. Early diagnosis and novel nonantibiotic methods are highly important for managing BIs. Thus, this review focuses on the epidemiology, prognosis, and diagnosis of and management strategies for BIs in ACLF patients as well as the relationship between BIs and ACLF.

scholarly journals Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis

Gut ◽  
2017 ◽  
Vol 67 (10) ◽  
pp. 1870-1880 ◽  
Author(s):  
Javier Fernández ◽  
Juan Acevedo ◽  
Reiner Wiest ◽  
Thierry Gustot ◽  
Alex Amoros ◽  
...  
Keyword(s):  
Liver Failure ◽  
Systemic Inflammation ◽  
Bacterial Infections ◽  
Clinical Course ◽  
Fungal Infections ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Bacterial Peritonitis ◽  
Probability Of Survival

Bacterial infection is a frequent trigger of acute-on-chronic liver failure (ACLF), syndrome that could also increase the risk of infection. This investigation evaluated prevalence and characteristics of bacterial and fungal infections causing and complicating ACLF, predictors of follow-up bacterial infections and impact of bacterial infections on survival.Patients407 patients with ACLF and 235 patients with acute decompensation (AD).Results152 patients (37%) presented bacterial infections at ACLF diagnosis; 46%(n=117) of the remaining 255 patients with ACLF developed bacterial infections during follow-up (4 weeks). The corresponding figures in patients with AD were 25% and 18% (p<0.001). Severe infections (spontaneous bacterial peritonitis, pneumonia, severe sepsis/shock, nosocomial infections and infections caused by multiresistant organisms) were more prevalent in patients with ACLF. Patients with ACLF and bacterial infections (either at diagnosis or during follow-up) showed higher grade of systemic inflammation at diagnosis of the syndrome, worse clinical course (ACLF 2-3 at final assessment: 47% vs 26%; p<0.001) and lower 90-day probability of survival (49% vs 72.5%;p<0.001) than patients with ACLF without infection. Bacterial infections were independently associated with mortality in patients with ACLF-1 and ACLF-2. Fungal infections developed in 9 patients with ACLF (2%) and in none with AD, occurred mainly after ACLF diagnosis (78%) and had high 90-day mortality (71%).ConclusionBacterial infections are extremely frequent in ACLF. They are severe and associated with intense systemic inflammation, poor clinical course and high mortality. Patients with ACLF are highly predisposed to develop bacterial infections within a short follow-up period and could benefit from prophylactic strategies.

scholarly journals Macrophages in Chronic Liver Failure: Diversity, Plasticity and Therapeutic Targeting

2021 ◽  
Vol 12 ◽  
Author(s):  
Arjuna Singanayagam ◽  
Evangelos Triantafyllou
Keyword(s):  
Liver Failure ◽  
Bacterial Infections ◽  
Cell Activation ◽  
Immune Cell ◽  
Cell Damage ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Bacterial Peritonitis ◽  
Disease States ◽  
Macrophage Populations

Chronic liver injury results in immune-driven progressive fibrosis, with risk of cirrhosis development and impact on morbidity and mortality. Persistent liver cell damage and death causes immune cell activation and inflammation. Patients with advanced cirrhosis additionally experience pathological bacterial translocation, exposure to microbial products and chronic engagement of the immune system. Bacterial infections have a high incidence in cirrhosis, with spontaneous bacterial peritonitis being the most common, while the subsequent systemic inflammation, organ failure and immune dysregulation increase the mortality risk. Tissue-resident and recruited macrophages play a central part in the development of inflammation and fibrosis progression. In the liver, adipose tissue, peritoneum and intestines, diverse macrophage populations exhibit great phenotypic and functional plasticity determined by their ontogeny, epigenetic programming and local microenvironment. These changes can, at different times, promote or ameliorate disease states and therefore represent potential targets for macrophage-directed therapies. In this review, we discuss the evidence for macrophage phenotypic and functional alterations in tissue compartments during the development and progression of chronic liver failure in different aetiologies and highlight the potential of macrophage modulation as a therapeutic strategy for liver disease.

scholarly journals Cohort profile: a multicentre prospective validation cohort of the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e037793
Author(s):  
Liang Qiao ◽  
Xianbo Wang ◽  
Guohong Deng ◽  
Yan Huang ◽  
Jinjun Chen ◽  
...  
Keyword(s):  
Liver Failure ◽  
Validation Cohort ◽  
Laboratory Data ◽  
Clinical Syndrome ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Life Study ◽  
Standard Medical Therapy ◽  
Short Term Mortality ◽  
Liver Injure

PurposeAcute-on-chronic liver failure (ACLF) is a clinical syndrome with high short-term mortality, unclear mechanism and controversial diagnosis criteria. The Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study has been conducted in China to fill the gaps. In the first phase (the CATCH-LIFE investigation cohort), 2600 patients were continuously recruited from 14 national nationwide liver centres from 12 different provinces of China in 2015–2016, and a series of important results were obtained. To validate the preliminary results, we designed and conducted this multicentre prospective observational cohort (the CATCH-LIFE validation cohort).ParticipantsPatients diagnosed with chronic liver disease and hospitalised for acute decompensation (AD) or acute liver injure were enrolled, received standard medical therapy. We collected the participants’ demographics, medical history, laboratory data, and blood and urine samples during their hospitalisation.Findings to dateFrom September 2018 to March 2019, 1370 patients (73.4% men) aged from 15 to 79 years old were enrolled from 13 nationwide liver centres across China. Of these patients, 952 (69.5%) had chronic hepatitis B, 973 (71.1%) had cirrhosis and 1083 (79.1%) complicated with AD at admission. The numbers and proportions of enrolled patients from each participating centre and the patients’ baseline characteristics are presented.Future plansA total of 12 months is required for each participant to complete follow-up. Outcome information (survival, death or receiving liver transplantation) collection and data cleansing will be done before June 2020. The data in the CATCH-LIFE validation cohort will be used for comparison between the new ACLF diagnostic criteria derivated from the CATCH-LIFE investigation cohort with existing ones. Moreover, future proteomic and metabolic omics analyses will provide valuable insights into the mechanics of ACLF, which will promote the development of specific therapy that leads to decrease patients’ mortality.RegistrationNCT03641872.

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.

Clinical Features of Hepatitis C Virus-Related Acute-On-Chronic Liver Failure in a Korean Population

2021 ◽  
Author(s):  
Jung Woo Choi ◽  
Jin-Kyu Cho ◽  
Sang Soo Lee ◽  
Jae Heon Kim ◽  
Hankyu Jeon ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Liver Failure ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Short Term ◽  
B Virus ◽  
Short Term Mortality ◽  
Very High

Abstract Background Acute-on-chronic liver failure (ACLF) is a widely recognized concept in which acute decompensation (AD) in patients with cirrhosis results in organ failures and high short-term mortality. However, few studies reflecting the various etiologies of cirrhosis are available. We aimed to investigate the clinical features of patients with hepatitis C virus (HCV)-related ACLF. Methods Between January 2005 and December 2018, 109 HCV-related cirrhosis patients who were hospitalized for AD (ascites, hepatic encephalopathy, gastrointestinal hemorrhage, and/or bacterial infection) were enrolled for ACLF defined by European Association for the Study of the Liver (EASL). Results ACLF developed in 35 patients (32.1%) on admission. Eight patients had ACLF grade 1, eight had ACLF grade 2, and 19 had ACLF grade 3. The 28-day and 90-day mortality rates were very low (2.7% and 5.4%, respectively) in patients without ACLF and very high (60.0% and 74.3%, respectively) in those with ACLF. In patients with HCV-related ACLF, the prevalence of liver failure was very low (17.1%), whereas that of kidney failure was very high (71.4%) compared to previous studies on hepatitis B virus-related ACLF and alcohol-related ACLF. Compared with all other prognostic scores, Chronic liver failure Consortium Organ Failure score most accurately predicted 90-day mortality, with an area under the receiver operator characteristic of 0.921. Conclusions HCV-related ACLF has unique clinical characteristics that are distinct from hepatitis B virus-related and alcohol-related ACLF. ACLF defined by EASL can be useful in predicting short-term mortality in HCV-related cirrhosis.

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.

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