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

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

Intensive Care Unit Care of a Patient with Cirrhosis.

Patients with cirrhosis frequently require admission to the intensive care unit (ICU). Common indications for admission to ICU include one or more reasons of sepsis, shock due to any cause, acute gastrointestinal bleeding, and altered mentation either due to hepatic encephalopathy, alcohol withdrawal/intoxication, or metabolic encephalopathy. The appropriate critical care of an individual can determine the outcomes of these sick patients. The Airway, Breathing, Circulation, Disability (ABCD) approach to a patient admitted to ICU includes airway, breathing, circulation, and disability management. In this review, the authors discuss the common indications for ICU admission in a patient with cirrhosis and also their management.

Infecciones diferentes a la peritonitis bacteriana espontánea en pacientes con cirrosis / Infections other than spontaneous bacterial peritonitis in patients with cirrhossis

Patients with cirrhosis are regularly infected with a plethora of bacteria, fungi and mycobacteria. A high index of suspicion of infection and a low threshold for culturing, ascitic fluid, blood, urine, pleural fluid, spinal fluid, joint fluid, etc will lead to a rapid diagnosis of infection and perhaps prolong survival of these very fragile patients.