Extracellular vesicles are membrane-bound vesicles containing proteins, lipids, RNAs and microRNAs. They can originate from both healthy and stressed cells, and provide a snapshot of the cell of origin in physiological and pathological circumstances. Various processes that may give rise to the release of extracellular vesicles occur in liver diseases, including hepatocyte apoptosis, hepatic stellate cell activation, liver innate immune system activation, systemic inflammation, and organelle dysfunction (mitochondrial dysfunction and endoplasmic reticulum stress). Numerous studies have therefore investigated the potential role of extracellular vesicles as biomarkers in liver diseases. This review provides an overview of the methods that can be used to measure extracellular vesicle concentrations in clinical settings, ranging from plasma preparation to extracellular vesicle measurement techniques, as well as looking at the challenges of using extracellular vesicles as biomarkers. We also provide a comprehensive review of studies that test extracellular vesicles as diagnostic, severity and prognostic biomarkers in various liver diseases, including non-alcoholic and alcoholic steatohepatitis, viral hepatitis B and C infections, cirrhosis, primary liver cancers, primary sclerosing cholangitis and acute liver failure. In particular, extracellular vesicles could be useful tools to evaluate activity and fibrosis in non-alcoholic fatty liver disease, predict risk of hepatitis B virus reactivation, predict complications and mortality in cirrhosis, detect early hepatocellular carcinoma, detect malignant transformation in primary sclerosing cholangitis and predict outcomes in acute liver failure. While most studies draw on data derived from pilot studies, which still require clinical validation, some extracellular vesicle subpopulations have already been evaluated in solid prospective studies.

Background SARS coronavirus 2 (SARS-CoV-2) is responsible for high morbidity and mortality worldwide, mostly due to the exacerbated inflammatory response observed in critically ill patients. However, little is known about the kinetics of the systemic immune response and its association with survival in SARS-CoV-2+ patients admitted in ICU. We aimed to compare the immuno-inflammatory features according to organ failure severity and in-ICU mortality. Methods Six-week multicentre study (N = 3) including SARS-CoV-2+ patients admitted in ICU. Analysis of plasma biomarkers at days 0 and 3–4 according to organ failure worsening (increase in SOFA score) and 60-day mortality. Results 101 patients were included. Patients had severe respiratory diseases with PaO2/FiO2 of 155 [111–251] mmHg), SAPS II of 37 [31–45] and SOFA score of 4 [3–7]. Eighty-three patients (83%) required endotracheal intubation/mechanical ventilation and among them, 64% were treated with prone position. IL-1β was barely detectable. Baseline IL-6 levels positively correlated with organ failure severity. Baseline IL-6 and CRP levels were significantly higher in patients in the worsening group than in the non-worsening group (278 [70–622] vs. 71 [29–153] pg/mL, P < 0.01; and 178 [100–295] vs. 100 [37–213] mg/L, P < 0.05, respectively). Baseline IL-6 and CRP levels were significantly higher in non-survivors compared to survivors but fibrinogen levels and lymphocyte counts were not different between groups. After adjustment on SOFA score and time from symptom onset to first dosage, IL-6 and CRP remained significantly associated with mortality. IL-6 changes between Day 0 and Day 3–4 were not different according to the outcome. A contrario, kinetics of CRP and lymphocyte count were different between survivors and non-survivors. Conclusions In SARS-CoV-2+ patients admitted in ICU, a systemic pro-inflammatory signature was associated with clinical worsening and 60-day mortality.