Circulating extracellular vesicles induce monocyte dysfunction and are associated with sepsis and high mortality in cirrhosis

Background Sepsis is common in cirrhosis and often a result of immune dysregulation. Specific stimuli pathways inter-cellular communications between cells sepsis are incompletely understood. Immune cell-derived extracellular vesicles (EV) were studied to understand mechanisms cirrhosis. Methods EV measured patients [Child-Turcotte-Pugh (Child) score A, n = 15; B 16; C 43 Child-C with (n 38)], healthy controls (HC, 11). In vitro vivo functional relevance associated was investigated. Results Monocyte, neutrophil hematopoietic stem progressively increased higher Child (P < .001)and correlated liver disease severity indices (r2 > 0.3, P .001), which further than without sepsis(P .001); monocyte showing the highest association stage [P .013; Odds ratio-4.14(1.34-12.42)]. A threshold level 53/µl predicted mortality [Odds ratio-6.2 (2.4-15.9), AUROC 0.76, .01]. from cirrhotic compared sepsis, induced mobilization arrest monocytes within 4 hours .004), reduced basal oxygen consumption rate .001) pro-inflammatory genes .05). The septic-EV on adoptive transfer C57/BL6J mice, sepsis-like condition 24 h leukocytopenia .005), intrahepatic inflammation CD11b + .03) bone marrow hyperplasia .01). Conclusion Extracellular induce impairment circulating contribute development perpetuation sepsis. High levels correlate can help early stratification sicker patients.