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

Christos Triantos; Maria Kalafateli; Stelios F Assimakopoulos; Katerina Karaivazoglou; Aikaterini Mantaka; Ioanna Aggeletopoulou; Panagiota I Spantidea; Georgios Tsiaoussis; Maria Rodi; Hariklia Kranidioti; Dimitrios Goukos; Spilios Manolakopoulos; Charalambos Gogos; Dimitrios N Samonakis; Georgios L Daikos; Athanasia Mouzaki; Konstantinos Thomopoulos

doi:10.3389/fmed.2022.836306

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

Front Med (Lausanne). 2022 Mar 3:9:836306. doi: 10.3389/fmed.2022.836306. eCollection 2022.

Authors

Christos Triantos¹, Maria Kalafateli¹, Stelios F Assimakopoulos², Katerina Karaivazoglou¹, Aikaterini Mantaka³, Ioanna Aggeletopoulou^{1

4}, Panagiota I Spantidea⁴, Georgios Tsiaoussis¹, Maria Rodi⁴, Hariklia Kranidioti⁵, Dimitrios Goukos⁶, Spilios Manolakopoulos⁵, Charalambos Gogos², Dimitrios N Samonakis³, Georgios L Daikos⁶, Athanasia Mouzaki⁴, Konstantinos Thomopoulos¹

Affiliations

¹ Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, Patras, Greece.
² Department of Internal Medicine, University Hospital of Patras, Patras, Greece.
³ Department of Gastroenterology, University Hospital of Heraklion, Heraklion, Greece.
⁴ Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece.
⁵ 2nd Department of Internal Medicine, Hippokration General Hospital of Athens, Athens, Greece.
⁶ Department of Propedeutic Medicine, Laiko General Hospital, Athens, Greece.

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.

Copyright © 2022 Triantos, Kalafateli, Assimakopoulos, Karaivazoglou, Mantaka, Aggeletopoulou, Spantidea, Tsiaoussis, Rodi, Kranidioti, Goukos, Manolakopoulos, Gogos, Samonakis, Daikos, Mouzaki and Thomopoulos.