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 (p0.3, p<0.001), which further increased in Child C sepsis than without sepsis(p<0.001); monocyte EV showing the highest association with disease stage [p=0.013; 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<0.01]. In vitro EV from cirrhotic with sepsis compared without sepsis, induced mobilization arrest in healthy monocytes within 4 hours (p=0.004), reduced basal oxygen consumption rate (p<0.001) and induced pro-inflammatory genes (p<0.05). The septic-EV on adoptive transfer to C57/BL6J mice, induced sepsis like condition within 24h with leukocytopenia (p=0.005), intrahepatic inflammation with increased CD11b+ cells (p=0.03) and bone marrow hyperplasia (p<0.01). 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

Asian Pacific association for the study of liver (APASL) guidelines: hepatitis B virus in pregnancy

Hepatitis B virus (HBV) infection still remains a major public health issue in the Asia-Pacific region. Most of the burden of HBV-related disease results from infections acquired in infancy through perinatal or early childhood exposure to HBV in Asia-Pacific. Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These APASL guidelines provide a comprehensive review and recommendations based on available evidence in the literature, for the management of females with HBV infection through every stage of pregnancy and postpartum. These also address the concerns, management challenges, and required follow-up of children born to hepatitis B-positive mothers