2022
DOI: 10.1016/j.jhep.2021.08.009
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Mitochondrial dysfunction governs immunometabolism in leukocytes of patients with acute-on-chronic liver failure

Abstract: This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, a… Show more

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Cited by 66 publications
(70 citation statements)
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“…Therefore, M1 macrophage activation is strengthened by a low α-ketoglutarate/succinate ratio ( Liu et al, 2017 ). Recently, we could demonstrate that the break point at SDH also exists in peripheral mononuclear cells of patients with ACLF ( 1 in Figure 1 ), probably as a consequence of systemic inflammation in these patients ( Zhang et al, 2021 ). This finding also generates the hypothesis that the break point serves to perpetuate the inflammatory responses through production of cytokines, which is promoted by the pro-inflammatory actions of succinate.…”
Section: Immunometabolism In the Setting Of Advanced Liver Disease: Role Of The Tricarboxylic Acid Cyclementioning
confidence: 88%
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“…Therefore, M1 macrophage activation is strengthened by a low α-ketoglutarate/succinate ratio ( Liu et al, 2017 ). Recently, we could demonstrate that the break point at SDH also exists in peripheral mononuclear cells of patients with ACLF ( 1 in Figure 1 ), probably as a consequence of systemic inflammation in these patients ( Zhang et al, 2021 ). This finding also generates the hypothesis that the break point serves to perpetuate the inflammatory responses through production of cytokines, which is promoted by the pro-inflammatory actions of succinate.…”
Section: Immunometabolism In the Setting Of Advanced Liver Disease: Role Of The Tricarboxylic Acid Cyclementioning
confidence: 88%
“…Increased numbers of mitochondria and swelling in circulating leukocytes of patients with AD cirrhosis (Zhang et al, 2021) Mitochondrial structure Systemic oxidative stress in patients with compensated and decompensated cirrhosis (Alcaraz-Quiles et al, 2018) Oxidative stress Decreased hepatic expression of COX1 and COX2 in cirrhotic patients (CHILD-Pugh A-C) (Nishikawa et al, 2014) OXPHOS Elevated serum mtDNA levels in patients with NASH-associated cirrhosis (An et al, 2020) Mitochondrial DAMPs…”
Section: Cirrhosismentioning
confidence: 99%
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“…Previous reports correlated the ACLF prognosis with glycolysis metabolic dysregulation and inhibition of mitochondrial energy production ( Moreau et al, 2020 ; Li et al, 2021 ). A recent study assessed the mitochondrial morphology and central metabolic pathways with emphasis on the tricarboxylic acid (TCA) cycle, and the findings leverage the appreciation for the role of mitochondrial dysfunction in the advanced liver diseases ( Zhang et al, 2021 ). Taken together, these findings revealed immune-metabolism disorder as the core mechanism underlying ACLF development and prognosis; in this context our model resembles the human clinical ACLF manifestations, regardless of the ACLF disease etiology and/or precipitating event.…”
Section: Discussionmentioning
confidence: 99%