Differential inflammasome activation predisposes to acute-on-chronic liver failure in human and experimental cirrhosis with and without previous decompensation.
Acute-On-Chronic Liver Failure
/ etiology
Adult
Aged
Aged, 80 and over
Animals
Female
Humans
Inflammasomes
/ adverse effects
Interleukin-1alpha
/ blood
Interleukin-1beta
/ blood
Liver Cirrhosis
/ complications
Liver Cirrhosis, Experimental
/ complications
Male
Middle Aged
Prospective Studies
Rats
Rats, Sprague-Dawley
inflammation
liver cirrhosis
portal hypertension
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
25
10
2019
revised:
18
03
2020
accepted:
21
03
2020
pubmed:
4
4
2020
medline:
8
9
2021
entrez:
4
4
2020
Statut:
ppublish
Résumé
Systemic 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. 249 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. Patients 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. Previous 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.
Identifiants
pubmed: 32241903
pii: gutjnl-2019-320170
doi: 10.1136/gutjnl-2019-320170
pmc: PMC7815638
doi:
Substances chimiques
IL1A protein, human
0
IL1B protein, human
0
Inflammasomes
0
Interleukin-1alpha
0
Interleukin-1beta
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
379-387Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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