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

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

doi:10.3389/fmed.2022.836306

Abstract

BackgroundBacterial infections are associated with the risk of variceal bleeding through complex pathophysiologic pathways.ObjectivesThe 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.MethodsEighty-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.ResultsChild-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.ConclusionsBacterial 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.

Highlights

Acute variceal bleeding is a serious complication of liver cirrhosis associated with significant morbidity and mortality [1–3]
The inclusion of prophylactic antibiotic treatment in current treatment guidelines is based on the notion that infection is a prognostic mortality factor [7, 8] and can trigger variceal bleeding via a complex cascade of pathophysiologic events, including endotoxin release, endothelin activation, and portal hypertension [7, 9, 10]
The study protocol was approved by the Scientific Review Board and the Ethics Committee of Patras University General Hospital (PUH) as part of a general application to collect biological samples from patients attending the hepatology clinics to study factors involved in the pathogenesis of liver cirrhosis

Summary

Introduction

Acute variceal bleeding is a serious complication of liver cirrhosis associated with significant morbidity and mortality [1–3]. Current treatment guidelines [4–6], which include early administration of vasoactive drugs, antibiotic prophylaxis, and band ligation, have resulted in increased survival [2]. The inclusion of prophylactic antibiotic treatment in current treatment guidelines is based on the notion that infection is a prognostic mortality factor [7, 8] and can trigger variceal bleeding via a complex cascade of pathophysiologic events, including endotoxin release, endothelin activation, and portal hypertension [7, 9, 10]. Bacterial infection has been shown to be strongly associated with variceal bleeding and failure to control bleeding [7]. The role of bacterial translocation in the pathogenesis of variceal bleeding has not been fully elucidated [14]. Bacterial infections are associated with the risk of variceal bleeding through complex pathophysiologic pathways

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