Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF DOI Creative Commons
Emmanuel Weiss, Pierre de la Grange,

Mylène Defaye

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 11

Published: Feb. 5, 2021

Background and Aims Patients with cirrhosis acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate simultaneously the major blood-immune cell subsets these patients. Material Methods Blood taken from 67 patients decompensated (including 35 critically ill ACLF intensive care unit), 12 healthy subjects, assigned either measurements clinical blood counts microarray (genomewide) analysis RNA expression whole-blood; neutrophils; or assessment neutrophil antimicrobial functions. Results Several features were found not those without ACLF. Indeed, count showed that characterized leukocytosis, neutrophilia, lymphopenia. Using CIBERSORT method deconvolute whole-blood RNA-expression data, revealed hallmark association neutrophilia increased proportions macrophages M0-like monocytes decreased memory lymphocytes (of B-cell, CD4 T-cell lineages), CD8 T cells natural killer cells. Microarray neutrophils had a unique phenotype including induction glycolysis granule genes, downregulation cell-migration cell-cycle genes. Moreover, defective production superoxide anion. Conclusions Genomic that, among cirrhosis, dysregulation immune cells, increases (that phenotype) monocytes, depletion several lymphocyte lymphocytes). All alterations, along anion production, may contribute immunosuppression ACLF, suggesting targets for future therapies.

Language: Английский

Global epidemiology of cirrhosis — aetiology, trends and predictions DOI Open Access
Daniel Q. Huang, Norah A. Terrault, Frank Tacke

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(6), P. 388 - 398

Published: March 28, 2023

Language: Английский

Citations

375
The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis DOI Creative Commons
Vicente Arroyo, Paolo Angeli, Richard Moreau

et al.

Journal of Hepatology, Journal Year: 2020, Volume and Issue: 74(3), P. 670 - 685

Published: Dec. 7, 2020

Acute decompensation (AD) of cirrhosis is defined by the development ascites, hepatic encephalopathy and/or variceal bleeding. Ascites traditionally attributed to splanchnic arterial vasodilation and left ventricular dysfunction, hyperammonaemia, haemorrhage portal hypertension. Recent large-scale European observational studies have shown that systemic inflammation a hallmark AD. Here we present working hypothesis, suggesting through an impairment functions one or more major organ systems may be common theme act synergistically with traditional mechanisms involved in Systemic impair system function which are not mutually exclusive. The first mechanism nitric oxide-mediated accentuation preexisting vasodilation, resulting overactivation endogenous vasoconstrictor elicit intense vasoconstriction hypoperfusion certain vascular beds, particular renal circulation. Second, cause immune-mediated tissue damage, process called immunopathology. Finally, induce important metabolic changes. Indeed, inflammatory responses energetically expensive processes, requiring reallocation nutrients (glucose, amino acids lipids) fuel immune activation. also inhibits nutrient consumption peripheral (non-immune) organs, effect provide prioritisation fuels for responses. However, decrease organs result decreased mitochondrial production ATP (energy) subsequently impaired function.

Language: Английский

Citations

316
Cirrhosis-associated immune dysfunction DOI
Agustı́n Albillos, Rosa Martín‐Mateos, Van der Merwe

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2021, Volume and Issue: 19(2), P. 112 - 134

Published: Oct. 26, 2021

Language: Английский

Citations

253
Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction DOI
Cornelius Engelmann, J. J. Clariá, Gyöngyi Szabó

et al.

Journal of Hepatology, Journal Year: 2021, Volume and Issue: 75, P. S49 - S66

Published: May 23, 2021

Language: Английский

Citations

252
A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis DOI Open Access
Louise China, Nick Freemantle, Ewan Forrest

et al.

New England Journal of Medicine, Journal Year: 2021, Volume and Issue: 384(9), P. 808 - 817

Published: March 3, 2021

Infection and increased systemic inflammation cause organ dysfunction death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflammatory role of albumin, but confirmatory large-scale clinical trials are lacking. Whether targeting a serum albumin level 30 g per liter or greater these repeated daily infusions 20% human solution, as compared standard care, would reduce the incidences infection, kidney dysfunction, is unknown.

Language: Английский

Citations

250
PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis DOI Creative Commons
Jonel Trebicka, Javier Fernández, Mária Papp

et al.

Journal of Hepatology, Journal Year: 2020, Volume and Issue: 74(5), P. 1097 - 1108

Published: Nov. 20, 2020

Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading both these AD phenotypes. The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients (No = 1,071; 202). Medical history, clinical data laboratory were collected at enrolment during 90-day follow-up, particular attention given following characteristics precipitants: induction dysfunction failure, systemic inflammation, chronology, intensity, relationship outcome. Among various events, 4 distinct events consistently related AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding shock toxic encephalopathy. in AD-No cohort AD-ACLF (38% 71%, respectively), almost all (96% 97%, respectively) showed infection either alone combination other events. Survival was similar infections hepatitis number associated significantly increased mortality paralleled increasing levels surrogates for inflammation. Importantly, adequate first-line antibiotic treatment a lower development rate mortality. This identified that are course prognosis AD. Specific preventive therapeutic strategies targeting improve outcomes decompensated cirrhosis. is characterized rapid deterioration patient health. precipitating cause Proven combination, accounted (96-97%) cases failure. Whilst type precipitant not mortality, precipitant(s) was. outcomes.

Language: Английский

Citations

215
EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis DOI Open Access
Erica Villa, Marcello Bianchini, Annabel Blasi

et al.

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 76(5), P. 1151 - 1184

Published: March 15, 2022

Language: Английский

Citations

212
The microbiota in cirrhosis and its role in hepatic decompensation DOI Creative Commons
Jonel Trebicka, Jane Macnaughtan, Bernd Schnabl

et al.

Journal of Hepatology, Journal Year: 2021, Volume and Issue: 75, P. S67 - S81

Published: May 23, 2021

Cirrhosis - the common end-stage of chronic liver disease is associated with a cascade events, which intestinal bacterial overgrowth and dysbiosis are central. Bacterial toxins entering portal or systemic circulation can directly cause hepatocyte death, while also affects gut barrier function increases translocation, leading to infections, inflammation vasodilation, contribute acute decompensation organ failure. Acute its severe forms, pre-acute-on-chronic failure (ACLF) ACLF, characterised by sudden dysfunction (and failure) high short-term mortality. Patients pre-ACLF ACLF present high-grade inflammation, usually precipitated proven infection and/or alcoholic hepatitis. However, no precipitant identified in 30% these patients, whom translocation from microbiota assumed be responsible for decompensation. Different profiles may influence rate thereby outcome patients. Thus, targeting promising strategy prevention treatment decompensation, ACLF. Approaches include use antibiotics such as rifaximin, faecal microbial transplantation enterosorbents (e.g. Yaq-001), bind factors without exerting direct effect on growth kinetics. This review focuses role strategies prevent

Language: Английский

Citations

176
Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis DOI
Gabriel Mezzano, Adrià Juanola, Andrés Cárdenas

et al.

Gut, Journal Year: 2021, Volume and Issue: 71(1), P. 148 - 155

Published: Jan. 12, 2021

Background and aims Acute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations ACLF across world in terms prevalence, mortality, aetiology chronic disease (CLD), triggers Methods searched EMBASE PubMed from 3/1/2013 to 7/3/2020 using ACLF-EASL-CLIF (European Association for Study Liver-Chronic Liver Failure) criteria. Two investigators independently conducted abstract selection/abstraction CLD, triggers, failures prevalence/mortality presence/grade ACLF. grouped countries into Europe, East/South Asia North/South America. calculated pooled proportions, methodological quality Newcastle-Ottawa Scale statistical heterogeneity, performed sensitivity analyses. Results identified 2369 studies; 30 cohort studies met our inclusion criteria (43 206 patients 140 835 without ACLF). The global prevalence among admitted decompensated was 35% (95% CI 33% 38%), highest South at 65%. 90-day mortality 58% 51% 64%), America 73%. Alcohol most frequently reported underlying CLD (45%, 95% 41 50). Infection frequent trigger (35%) kidney dysfunction common (49%). Sensitivity analyses showed regional estimates grossly unchanged high-quality studies. Type design, country health index, explained variation estimates. Conclusions are high. Region-specific could be type triggers/aetiology or grade. Health systems will need tailor early recognition treatment based on region-specific data.

Language: Английский

Citations

147
Utilizing the gut microbiome in decompensated cirrhosis and acute-on-chronic liver failure DOI
Jonel Trebicka, Peer Bork, Aleksander Krag

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2020, Volume and Issue: 18(3), P. 167 - 180

Published: Nov. 30, 2020

Language: Английский

Citations

145