Z Gastroenterol 2019; 57(01): e75
DOI: 10.1055/s-0038-1677247
5. Viral Hepatitis, Immunology
Georg Thieme Verlag KG Stuttgart · New York

Compartmentalization of immune response and microbial translocation in decompensated cirrhosis

C Alvarez-Silva
1   Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
,
R Schierwagen
2   Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany
3   Department of Internal Medicine I, University of Bonn, Bonn, Germany
,
A Pohlmann
3   Department of Internal Medicine I, University of Bonn, Bonn, Germany
,
F Magdaleno
3   Department of Internal Medicine I, University of Bonn, Bonn, Germany
,
FE Uschner
2   Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany
3   Department of Internal Medicine I, University of Bonn, Bonn, Germany
,
P Ryan
3   Department of Internal Medicine I, University of Bonn, Bonn, Germany
,
MJGT Vehreschild
4   Medical Clinic II, University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany
,
J Claria
5   European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
,
E Latz
6   Institute of Innate Immunity, University of Bonn, Bonn, Germany
7   Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA
8   German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
9   Centre for Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway
,
B Lelouvier
10   Vaiomer, Labège, France
,
M Arumugam
1   Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
11   Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
,
J Trebicka
2   Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany
3   Department of Internal Medicine I, University of Bonn, Bonn, Germany
5   European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
11   Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
› Author Affiliations
Further Information

Publication History

Publication Date:
04 January 2019 (online)

Also available at
 

Background:

Acquired dysfunctional immunity in cirrhosis predisposes patients to frequent bacterial infections, especially spontaneous bacterial peritonitis (SBP), leading to systemic inflammation. Systemic inflammation is also found in the absence of a confirmed infection and is associated with poor outcome. Detection of bacterial DNA has been investigated as a marker of SBP and as a predictor of prognosis. Data is, however contradictory. This study investigated whether cytokine levels produced by myeloid cells in ascites are associated with systemic inflammation and whether inflammation depends on the presence of specific bacterial species.

Methods and material:

We enrolled 33 patients with decompensated liver cirrhosis from whom we collected paired samples of blood and ascites. IL-6 and IL-8 were measured in serum samples of all patients using ELISA. In a subset of 10 representative patients, bacterial DNA was extracted from ascites and whole blood, followed by 16S rRNA gene amplicon sequencing.

Results:

There were significantly higher levels of IL-6 in ascites fluid compared to blood samples in all patients. Interestingly, IL-6 levels in blood correlated tightly with disease severity and surrogates of systemic inflammation, while IL-6 levels in ascites did not. Moreover, patients with higher blood CRP levels showed greater SBP prevalence compared to patients with lower levels, despite similar positive culture results. Bacterial richness was also significantly higher in ascites compared to the corresponding patient blood. We identified differences in microbial composition and diversity between ascites and blood, but no tight relationship with surrogates of systemic inflammation could be observed.

Discussion:

In decompensated cirrhosis, markers of systemic inflammation and microbiota composition seem to be dysregulated in ascites and blood. While a relationship between systemic inflammation and microbiota composition seems to exist in blood, this is not the case for ascites. These data suggest compartmentalization of the immune response and interaction of the latter with the microbiota especially in the blood compartment.