Endotoxemia and Platelets : 2 Players of Intrahepatic Microthrombosis in NAFLD

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Highlights

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  NAFLD is characterized by gut dysbiosis–related LPS translocation into portal circulation with ensuing LPS localization in the hepatocytes that overexpress TLR4, the LPS receptor.

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  This review discusses the experimental and clinical evidence on the interplay between LPS and platelet activation as mechanism potentially eliciting intrahepatic microthrombosis and eventually NAFLD focusing on the role of the LPS-TLR4 axis as the mechanism inducing platelet activation and liver inflammation.

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  Further study will be required to assess if reducing LPS translocation by lowering gut dysbiosis or detoxifying LPS may result in lowering intrahepatic microthrombosis and eventually NAFLD.

Summary

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.