Fungal translocation measured by serum 1,3-ß-D-glucan correlates with severity and outcome of liver cirrhosis-A pilot study.
1,3-β-D-glucan
gut
liver cirrhosis
microbiome
mycobiome
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
revised:
08
05
2023
received:
10
10
2022
accepted:
04
06
2023
medline:
14
8
2023
pubmed:
19
6
2023
entrez:
19
6
2023
Statut:
ppublish
Résumé
On a global scale, liver cirrhosis is attributable to ~1 million deaths per year. This systemic disease comes along with diverse sequelae, including microbiota alterations, increased gut permeability and translocation of microbial components into the systemic circulation. Alongside the extensively studied influence of bacterial translocation and its host-pathogen interactions, far less is known about the role and impact of fungal components once having crossed the intestinal barrier. Including 70 patients with different aetiologies of liver cirrhosis, we investigated the relationship between fungal translocation, measured by 1,3-β-D-glucan (BDG), and biomarkers of gut integrity, inflammation and severity/outcome of liver disease. Patients with cirrhosis Child-Pugh class (CPC)-B were more likely to have positive serum BDG (aOR 5.4, 95% CI 1.2-25.2) compared to patients with cirrhosis CPC-A. BDG showed a moderate positive correlation with several markers of inflammation (sCD206, sCD163, Interleukin 8, interferon-gamma-induced protein). Mortality differed significantly between patients with positive versus negative BDG (log-rank test, p = 0.015). The multivariable Cox regression model yielded an aHR of 6.8 (95% CI 1.8-26.3). We observed trends for increased fungal translocation depending on the severity of liver cirrhosis, an association of BDG with an inflammatory environment and the adverse effects of BDG on disease outcome. In order to gain more in-depth knowledge about (fungal-)dysbiosis and its detrimental consequences in the setting of liver cirrhosis, these trends need to be studied in more detail including prospective sequential testing in larger cohorts together with mycobiome analyses. This will further elucidate complex host-pathogen interactions and potentially introduce points of application for therapeutic interventions.
Sections du résumé
BACKGROUND & AIMS
On a global scale, liver cirrhosis is attributable to ~1 million deaths per year. This systemic disease comes along with diverse sequelae, including microbiota alterations, increased gut permeability and translocation of microbial components into the systemic circulation. Alongside the extensively studied influence of bacterial translocation and its host-pathogen interactions, far less is known about the role and impact of fungal components once having crossed the intestinal barrier.
METHODS
Including 70 patients with different aetiologies of liver cirrhosis, we investigated the relationship between fungal translocation, measured by 1,3-β-D-glucan (BDG), and biomarkers of gut integrity, inflammation and severity/outcome of liver disease.
RESULTS
Patients with cirrhosis Child-Pugh class (CPC)-B were more likely to have positive serum BDG (aOR 5.4, 95% CI 1.2-25.2) compared to patients with cirrhosis CPC-A. BDG showed a moderate positive correlation with several markers of inflammation (sCD206, sCD163, Interleukin 8, interferon-gamma-induced protein). Mortality differed significantly between patients with positive versus negative BDG (log-rank test, p = 0.015). The multivariable Cox regression model yielded an aHR of 6.8 (95% CI 1.8-26.3).
DISCUSSION
We observed trends for increased fungal translocation depending on the severity of liver cirrhosis, an association of BDG with an inflammatory environment and the adverse effects of BDG on disease outcome. In order to gain more in-depth knowledge about (fungal-)dysbiosis and its detrimental consequences in the setting of liver cirrhosis, these trends need to be studied in more detail including prospective sequential testing in larger cohorts together with mycobiome analyses. This will further elucidate complex host-pathogen interactions and potentially introduce points of application for therapeutic interventions.
Substances chimiques
Glucans
0
Biomarkers
0
beta-Glucans
0
Banques de données
ClinicalTrials.gov
['NCT01607528']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1975-1983Informations de copyright
© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.
Références
AIDS Res Hum Retroviruses. 2019 May;35(5):461-472
pubmed: 30784316
Mediators Inflamm. 1997;6(4):279-83
pubmed: 18472859
Mycoses. 2014 Nov;57(11):679-86
pubmed: 25040144
Front Microbiol. 2018 Apr 13;9:737
pubmed: 29706947
Chronic Obstr Pulm Dis. 2022 Jul 29;9(3):325-335
pubmed: 35550241
Hepatology. 2015 Mar;61(3):883-94
pubmed: 25251280
Shock. 2016 Nov;46(5):506-518
pubmed: 27172153
Clin Chem Lab Med. 2014 Mar;52(3):453-61
pubmed: 24114918
J Clin Invest. 2017 Jun 30;127(7):2829-2841
pubmed: 28530644
World J Gastroenterol. 2021 Mar 7;27(9):866-885
pubmed: 33727775
Diabetes. 2007 Jul;56(7):1761-72
pubmed: 17456850
Virulence. 2017 Apr 3;8(3):352-358
pubmed: 27736307
Front Public Health. 2022 Sep 14;10:981339
pubmed: 36187617
Mycoses. 2015 Jul;58(7):394-8
pubmed: 25959065
J Hepatol. 2014 May;60(5):940-7
pubmed: 24374295
J Acquir Immune Defic Syndr. 2012 Dec 1;61(4):462-8
pubmed: 22972021
J Hepatol. 2014 Jul;61(1):51-8
pubmed: 24681345
Front Immunol. 2016 Oct 03;7:404
pubmed: 27752257
BMC Nephrol. 2020 Apr 6;21(1):118
pubmed: 32252666
J Neurovirol. 2019 Dec;25(6):837-843
pubmed: 31297727
Clin Infect Dis. 2019 Aug 1;69(4):676-686
pubmed: 30418519
Open Forum Infect Dis. 2019 Jul 1;6(7):
pubmed: 31363763
Med Mycol. 2014 Jul;52(5):455-61
pubmed: 24906361
J Hepatol. 2016 Apr;64(4):813-22
pubmed: 26639396
Liver Int. 2023 Sep;43(9):1975-1983
pubmed: 37334864
Gastroenterology. 2014 May;146(6):1513-24
pubmed: 24440671
Pharmacol Res. 2018 Apr;130:143-151
pubmed: 29444477
Aliment Pharmacol Ther. 2016 Nov;44(9):926-935
pubmed: 27593544
Liver Int. 2018 Feb;38 Suppl 1:126-133
pubmed: 29427501
Scand J Clin Lab Invest. 2002;62(4):293-9
pubmed: 12476928
Mycoses. 2021 Jan;64(1):24-29
pubmed: 32780885
J Innate Immun. 2018;10(3):189-201
pubmed: 29393221
Clin Infect Dis. 2020 Jan 2;70(2):232-241
pubmed: 30877304
Lancet. 2021 Oct 9;398(10308):1359-1376
pubmed: 34543610
J Fungi (Basel). 2017 Oct 07;3(4):
pubmed: 29371572
Hepatogastroenterology. 2014 Jul-Aug;61(133):1368-73
pubmed: 25436313
Clin Infect Dis. 2020 Jan 2;70(2):242-244
pubmed: 30861074