Bacterial translocation occurs early in cirrhosis and triggers a selective inflammatory response.
Por:
Simbrunner B, Caparrós E, Neuwirth T, Schwabl P, Königshofer P, Bauer D, Marculescu R, Trauner M, Scheiner B, Stary G, Mandorfer M, Reiberger T and Francés R
Publicada:
7 mar 2023
Ahead of Print:
7 mar 2023
Resumen:
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-a 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-a (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-a 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.
Filiaciones:
Simbrunner B:
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
:
CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain
Hepatic and Intestinal Immunobiology Group, Department of Clinical Medicine, Miguel Hernández University, San Juan de Alicante, Elche, Spain
Instituto IDIBE, Miguel Hernández University, Elche, Spain
Neuwirth T:
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Department of Dermatology, Medical University of Vienna, Vienna, Austria
Schwabl P:
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Königshofer P:
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Bauer D:
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
Marculescu R:
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Trauner M:
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
Scheiner B:
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
Stary G:
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Department of Dermatology, Medical University of Vienna, Vienna, Austria
Mandorfer M:
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
Reiberger T:
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria.
Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria.
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
:
CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain
Hepatic and Intestinal Immunobiology Group, Department of Clinical Medicine, Miguel Hernández University, San Juan de Alicante, Elche, Spain
Instituto IDIBE, Miguel Hernández University, Elche, Spain
Instituto ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain
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