Figure 1.

Circulating EVs affect liver physiology and pathology. Pathophysiological conditions in both the liver and extrahepatic tissues provoke increases in circulating EVs that often accumulate in the liver and modulate pathophysiological responses. Liver-derived circulating EVs target circulating immune cells and extrahepatic tissues to transmit their pathophysiological conditions. Systemic pathophysiological conditions including aging, inflammation, metabolic dysfunction, gut dysbiosis, injury, viral infection, and cancer aggravate liver physiology and promote pathological status through EV-mediated modulation of energy homeostasis, immune responses, disease-associated phenotypes, and cancer progression. In the same way, pathophysiological liver conditions including abnormal energy homeostasis, inflammation, injury, viral infection, fibrosis, and cancer promote pathological responses in the blood and distant organs by delivering their EVs through the circulation. Schematic illustration was created with BioRender.com. DM, diabetes mellitus; DILI, drug-induced liver injury; IRI, ischemia-reperfusion injury; NK, natural killer; CVD, cardiovascular disease; EV, extracellular vesicle.