Gut microbiota-platelet axis and thrombosis in advanced chronic liver disease

: Advanced chronic liver disease is characterized by metabolic-associated liver disease, metabolic-associated steatohepatitis and cirrhosis. This clinical setting is associated with platelets' activation, that has been suggested to play a role in the progression of liver disease; thus, platelet activation has been detected in portal circulation as well within liver sinusoids. Experimental studies with antiplatelet drugs and observational studies in human suggested a role for platelet activation in the mechanism of the disease. Furthermore, advanced chronic liver disease may be complicated by atherosclerotic complications, where the role of platelet activation is well consolidated. Platelets' activation may represent a unique mechanism leading to liver disease on one hand and to atherosclerotic complications on the other hand. Several studies pointed to the role of gut dysbiosis as key step for eliciting platelets' activation via the production of pro-aggregating metabolites such as Trimethylamine N-oxide or translocation of bacterial products such as lipopolysaccharide into the systemic circulation. The aims of this narrative review are 1) to show experimental and clinical evidence relating platelets with advanced chronic liver disease, 2) to explore the role of gut microbiota as mechanism for platelets' activation, and 3) to suggest novel therapeutic strategy to inhibit gut microbiota-platelet axis.