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L’encéphalopathie hépatique au cours de la cirrhose, de la physiopathologie au traitement

Abstract : Hepatic encephalopathy (HE) is a severe complication of cirrhosis. Pathophysiology still debated. Hyperammonia involvement is well known. Systemic inflammation could participate, increasing blood brain barrier (BBB) permeability. Alterations of TCA cycle could exist too in HE (pilot study of metabolomic in cerebrospinal fluids of patients with HE). The objectives were : to define the different contributions of ammonia, systemic inflammation and suspected dysregulation of energetic metabolism using animal models of cirrhosis ; to study efficiency of differents drugs on the abnormalities. We used a behavioral test to evaluate HE on two models of cirrhosis (biliary-BDL and toxic-CCl4) versus controls. Treatments given were hyperammoniemic (NH3), hypoammoniemic (sodium benzoate-BNa), antibiotic (rifaximine-RFX) or aiming to restore TCA (biotine). Ammonemia, cytokins and BBB permeability measured by fluorimetry were evaluated. Ammonemia was higher in the two models BDL and CCl4 compared to controls ; BDL had HE and an increased permeability of BBB ; these modifications were not observed in CCl4. Cytokins were significantly higher in BDL than in CCl4. NH3 treatment did not potentiate HE nor BBB alteration. BNa, RFX and biotine prevent the development of HE and BBB abnormalities. Hyperammonia and inflammation could act synergistically in HE. Innovating efficiency of biotine in HE could open new perspectives of pathophysiology pathway and therapeutic tools.
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https://tel.archives-ouvertes.fr/tel-03189283
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Submitted on : Saturday, April 3, 2021 - 1:01:30 AM
Last modification on : Monday, April 12, 2021 - 3:52:43 PM

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  • HAL Id : tel-03189283, version 1

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Sarah Mouri. L’encéphalopathie hépatique au cours de la cirrhose, de la physiopathologie au traitement. Médecine humaine et pathologie. Sorbonne Université, 2019. Français. ⟨NNT : 2019SORUS250⟩. ⟨tel-03189283⟩

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