In:
Hepatology International, Springer Science and Business Media LLC, Vol. 17, No. 4 ( 2023-08), p. 1045-1056
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1936-0533
,
1936-0541
DOI:
10.1007/s12072-023-10496-y
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
2270316-0
