Endotoxemia and Platelets: 2 Players of Intrahepatic Microthrombosis in NAFLD

Francesco Violi; Daniele Pastori; Pasquale Pignatelli; Vittoria Cammisotto

doi:10.1016/j.jacbts.2023.07.003

Endotoxemia and Platelets: 2 Players of Intrahepatic Microthrombosis in NAFLD

JACC Basic Transl Sci. 2023 Sep 27;9(3):404-413. doi: 10.1016/j.jacbts.2023.07.003. eCollection 2024 Mar.

Authors

Francesco Violi¹, Daniele Pastori², Pasquale Pignatelli^{1

2}, Vittoria Cammisotto²

Affiliations

¹ Mediterranea Cardiocentro-Napoli, Naples, Italy.
² Department of Clinical Internal, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.

Abstract

Gut dysbiosis-related intestinal barrier dysfunction with increased translocation of bacterial products such as lipopolysaccharide (LPS) into systemic circulation is emerging as pathogenic factor of nonalcoholic fatty liver disease (NAFLD). Experimental and clinical studies suggested a potential role of LPS as a trigger eliciting in situ liver inflammation upon interaction with its receptor toll-like receptor 4. Also, LPS has been reported to prime platelets to respond to the common agonists indicating that it behaves as a prothrombotic molecule. Of note, recent studies suggested platelet-related intrahepatic thrombosis triggered by LPS as a mechanism implicated in the process of liver inflammation. This review describes: 1) the impact of gut barrier dysfunction and endotoxemia in the process of NAFLD; 2) the relationship between endotoxemia and platelet activation in NAFLD; 3) clinical evidence for the use of antiplatelet drugs in NAFLD/nonalcoholic steatohepatitis patients; and 4) the potential therapeutic approach to modulate endotoxemia and eventually platelet activation.

Keywords: NAFLD; lipopolysaccharide; platelet activation; thrombosis.

Publication types

Review