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. 2022 Mar 3:9:836306.
doi: 10.3389/fmed.2022.836306. eCollection 2022.

Endotoxin Translocation and Gut Barrier Dysfunction Are Related to Variceal Bleeding in Patients With Liver Cirrhosis

Christos Triantos  1 , Maria Kalafateli  1 , Stelios F Assimakopoulos  2 , Katerina Karaivazoglou  1 , Aikaterini Mantaka  3 , Ioanna Aggeletopoulou  1   4 , Panagiota I Spantidea  4 , Georgios Tsiaoussis  1 , Maria Rodi  4 , Hariklia Kranidioti  5 , Dimitrios Goukos  6 , Spilios Manolakopoulos  5 , Charalambos Gogos  2 , Dimitrios N Samonakis  3 , Georgios L Daikos  6 , Athanasia Mouzaki  4 , Konstantinos Thomopoulos  1
Affiliations

Endotoxin Translocation and Gut Barrier Dysfunction Are Related to Variceal Bleeding in Patients With Liver Cirrhosis

Christos Triantos et al. Front Med (Lausanne). .

Abstract

Background: Bacterial infections are associated with the risk of variceal bleeding through complex pathophysiologic pathways.

Objectives: The primary objective of the present case-control study was to investigate the role of bacterial translocation and intestinal barrier dysfunction in the pathogenesis of variceal bleeding. A secondary objective was to determine independent predictors of key outcomes in variceal bleeding, including bleeding-related mortality.

Methods: Eighty-four (n = 84) consecutive patients participated in the study, 41 patients with acute variceal bleeding and 43 patients with stable cirrhosis, and were followed up for 6 weeks. Peripheral blood samples were collected at patient admission and before any therapeutic intervention.

Results: Child-Pugh (CP) score (OR: 1.868; p = 0.044), IgM anti-endotoxin antibody levels (OR: 0.954; p = 0.016) and TGF-β levels (OR: 0.377; p = 0.026) were found to be significant predictors of variceal bleeding. Regression analysis revealed that albumin (OR: 0.0311; p = 0.023), CRP (OR: 3.234; p = 0.034) and FABP2 levels (OR:1.000, p = 0.040), CP score (OR: 2.504; p = 0.016), CP creatinine score (OR: 2.366; p = 0.008), end-stage liver disease model (MELD), Na (OR: 1.283; p = 0.033), portal vein thrombosis (OR: 0.075; p = 0.008), hepatocellular carcinoma (OR: 0.060; p = 0.003) and encephalopathy (OR: 0.179; p = 0.045) were significantly associated with 6-week mortality.

Conclusions: Bacterial translocation and gut barrier impairment are directly related to the risk of variceal bleeding. Microbiota-modulating interventions and anti-endotoxin agents may be promising strategies to prevent variceal bleeding.

Keywords: bacterial translocation; cirrhosis; intestinal barrier; liver-gut axis; variceal bleeding.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Comparison of serum laboratory parameters between patients with stable liver cirrhosis and patients presenting with variceal bleeding. Bars and plots represent the median and interquartile range, respectively. Asterisks indicate statistical significance (*p < 0.05; **p < 0.01).
Figure 2
Figure 2
Comparison of serum laboratory parameters between patients with controlled bleeding and patients with uncontrolled bleeding. Bars and plots represent median and interquartile range, respectively. Asterisks indicate statistical significance (*p < 0.05; **p < 0.01).
Figure 3
Figure 3
Comparison of serum laboratory parameters between 6-week survivors and non-survivors. Bars and plots represent median and interquartile range, respectively. Asterisks indicate statistical significance (*p < 0.05).
Figure 4
Figure 4
Schematic representation of our proposed mechanism for the contribution of bacterial translocation and increased gut permeability to variceal bleeding risk.
See this image and copyright information in PMC

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