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Bacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response

BACKGROUND: Experimental data suggest that bacterial translocation (BT) promotes systemic inflammation, portal hypertension, and circulatory dysfunction in advanced chronic liver disease (ACLD). METHODS: Patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement and absence of...

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Autores principales: Simbrunner, Benedikt, Caparrós, Esther, Neuwirth, Teresa, Schwabl, Philipp, Königshofer, Philipp, Bauer, David, Marculescu, Rodrig, Trauner, Michael, Scheiner, Bernhard, Stary, Georg, Mandorfer, Mattias, Reiberger, Thomas, Francés, Rubén
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer India 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10386924/
https://www.ncbi.nlm.nih.gov/pubmed/36881247
http://dx.doi.org/10.1007/s12072-023-10496-y
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author Simbrunner, Benedikt
Caparrós, Esther
Neuwirth, Teresa
Schwabl, Philipp
Königshofer, Philipp
Bauer, David
Marculescu, Rodrig
Trauner, Michael
Scheiner, Bernhard
Stary, Georg
Mandorfer, Mattias
Reiberger, Thomas
Francés, Rubén
author_facet Simbrunner, Benedikt
Caparrós, Esther
Neuwirth, Teresa
Schwabl, Philipp
Königshofer, Philipp
Bauer, David
Marculescu, Rodrig
Trauner, Michael
Scheiner, Bernhard
Stary, Georg
Mandorfer, Mattias
Reiberger, Thomas
Francés, Rubén
author_sort Simbrunner, Benedikt
collection PubMed
description BACKGROUND: Experimental data suggest that bacterial translocation (BT) promotes systemic inflammation, portal hypertension, and circulatory dysfunction in advanced chronic liver disease (ACLD). METHODS: Patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement and absence of acute decompensation or infections were included (n = 249). Serum biomarkers of BT (lipopolysaccharide [LPS], lipoteichoic acid [LTA], bacterial DNA [bactDNA]), systemic inflammation and markers of circulatory dysfunction were assessed. T-cell subsets in intestinal biopsies (n = 7 ACLD, n = 4 controls) were analyzed by flow cytometry. RESULTS: Patients had a median HVPG of 18 (12–21) mmHg and 56% had decompensated ACLD. LPS (0.04 [0.02–0.06] vs. 0.64 [0.30–1.06] EU/mL), LTA (4.53 [3.58–5.97] vs. 43.2 [23.2–109] pg/mL), and detection of bactDNA (≥ 5 pg/mL; 5% vs. 41%) were markedly higher in patients with ACLD than healthy controls (n = 40; p < 0.001) but were similar between different clinical stages of compensated and decompensated ACLD and displayed no meaningful correlation with HVPG and systemic hemodynamics. TNF-α and IL-10 correlated with LPS (Spearman’s r(s) = 0.523, p < 0.001/r(s) = 0.143, p = 0.024) but not with LTA. Presence of bactDNA was associated with higher LPS (0.54 [0.28–0.95] vs. 0.88 [0.32–1.31] EU/mL, p = 0.001) and TNF-α (15.3 [6.31–28.1] vs. 20.9 [13.8–32.9] pg/mL). Patients with ACLD exhibited a decreased CD4:CD8-ratio and increased T(H)1-cells in the intestinal mucosa as compared to controls. During a median FU of 14.7 (8.20–26.5) months, bacterial antigens did not predict decompensation or liver-related death (in contrast to HVPG, IL-6, and MAP) as well as infections at 24 months. CONCLUSION: BT occurs already in early ACLD stages and triggers a systemic inflammatory response via TNF-α and IL-10. Interestingly, BT markers showed no clear correlation with portal hypertension and circulatory dysfunction in patients with stable ACLD. CLINICAL TRIAL NUMBER: NCT03267615. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12072-023-10496-y.
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spelling pubmed-103869242023-07-31 Bacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response Simbrunner, Benedikt Caparrós, Esther Neuwirth, Teresa Schwabl, Philipp Königshofer, Philipp Bauer, David Marculescu, Rodrig Trauner, Michael Scheiner, Bernhard Stary, Georg Mandorfer, Mattias Reiberger, Thomas Francés, Rubén Hepatol Int Original Article BACKGROUND: Experimental data suggest that bacterial translocation (BT) promotes systemic inflammation, portal hypertension, and circulatory dysfunction in advanced chronic liver disease (ACLD). METHODS: Patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement and absence of acute decompensation or infections were included (n = 249). Serum biomarkers of BT (lipopolysaccharide [LPS], lipoteichoic acid [LTA], bacterial DNA [bactDNA]), systemic inflammation and markers of circulatory dysfunction were assessed. T-cell subsets in intestinal biopsies (n = 7 ACLD, n = 4 controls) were analyzed by flow cytometry. RESULTS: Patients had a median HVPG of 18 (12–21) mmHg and 56% had decompensated ACLD. LPS (0.04 [0.02–0.06] vs. 0.64 [0.30–1.06] EU/mL), LTA (4.53 [3.58–5.97] vs. 43.2 [23.2–109] pg/mL), and detection of bactDNA (≥ 5 pg/mL; 5% vs. 41%) were markedly higher in patients with ACLD than healthy controls (n = 40; p < 0.001) but were similar between different clinical stages of compensated and decompensated ACLD and displayed no meaningful correlation with HVPG and systemic hemodynamics. TNF-α and IL-10 correlated with LPS (Spearman’s r(s) = 0.523, p < 0.001/r(s) = 0.143, p = 0.024) but not with LTA. Presence of bactDNA was associated with higher LPS (0.54 [0.28–0.95] vs. 0.88 [0.32–1.31] EU/mL, p = 0.001) and TNF-α (15.3 [6.31–28.1] vs. 20.9 [13.8–32.9] pg/mL). Patients with ACLD exhibited a decreased CD4:CD8-ratio and increased T(H)1-cells in the intestinal mucosa as compared to controls. During a median FU of 14.7 (8.20–26.5) months, bacterial antigens did not predict decompensation or liver-related death (in contrast to HVPG, IL-6, and MAP) as well as infections at 24 months. CONCLUSION: BT occurs already in early ACLD stages and triggers a systemic inflammatory response via TNF-α and IL-10. Interestingly, BT markers showed no clear correlation with portal hypertension and circulatory dysfunction in patients with stable ACLD. CLINICAL TRIAL NUMBER: NCT03267615. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12072-023-10496-y. Springer India 2023-03-07 /pmc/articles/PMC10386924/ /pubmed/36881247 http://dx.doi.org/10.1007/s12072-023-10496-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Simbrunner, Benedikt
Caparrós, Esther
Neuwirth, Teresa
Schwabl, Philipp
Königshofer, Philipp
Bauer, David
Marculescu, Rodrig
Trauner, Michael
Scheiner, Bernhard
Stary, Georg
Mandorfer, Mattias
Reiberger, Thomas
Francés, Rubén
Bacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response
title Bacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response
title_full Bacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response
title_fullStr Bacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response
title_full_unstemmed Bacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response
title_short Bacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response
title_sort bacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10386924/
https://www.ncbi.nlm.nih.gov/pubmed/36881247
http://dx.doi.org/10.1007/s12072-023-10496-y
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