Changes in plasma circulating microvesicles in patients with HCV‐related cirrhosis after treatment with direct‐acting antivirals

Abstract

Background & Aims The eradication of Hepatitis C (HCV) infection by direct‐acting antiviral (DAAs) agents has been linked to an amelioration of liver synthesis and regression of fibrosis. Although changes in number and type of circulating microvesicles (MVs) have been reported in cirrhosis, conclusive data on the effect of DAAs treatment on MVs profile in HCV cirrhotic patients remain scarce. Methods We measured the levels of endothelial, platelet and hepatocyte MVs, as well as MVs‐expressing versican core protein (VCAN+) in patients with HCV‐related cirrhosis at baseline, end of treatment (EOT), at 12, 24 and 48 weeks (W) after EOT by new generation flow cytometry. Results Fifty‐eight patients were enrolled (86% Child's A). MVs were increased at EOT vs baseline, though only platelet MVs revealed a statistically significant difference (P < .01). MV levels did not change significantly after EOT notwithstanding a steady downward trend towards baseline levels. Conversely, VCAN + MVs dropped significantly at EOT (P < .001) and remained low throughout the follow‐up. Hepatocyte MVs significantly correlated with liver stiffness (r = .40, P = .0021). Eight composite outcomes occurred during the 1‐year follow‐up: three portal vein thromboses (PVTs), two hepatocellular carcinomas (HCCs) and three liver decompensation. Child's B, the presence of F2 oesophageal varices (OR for interaction 19.2 [95% CI 1.45‐253.7], P = .023) and platelet MVs (OR 1.026 [95% CI 1.00‐1.05, P = .023) correlated significantly with clinical outcomes. Conclusions VCAN + MVs appear to mirror the profibrotic status of the cirrhotic disease; hepatocyte MVs correlate with liver stiffness and increased platelet MV levels could be associated with a worse clinical outcome.

Extracellular vesicles as biomarkers in liver diseases: A clinician's point of view

“…These studies are discussed in the supplementary text. 39,47,125,126,135,[138][139][140][141][142] Prediction of mortality In a prospective collaborative study, including a validation cohort, we demonstrated that plasma levels of hepatocyte-derived extracellular vesicles can predict 6-month mortality, independently of Child-Pugh and MELD scores, using a threshold of 65 IU/L. 40 In this study, other subpopulations of plasma extracellular vesicles, including panleukocyte (CD11+) and endothelial (CD144+, CD62E+), were not useful for predicting mortality.…”

Platelet-Derived Microparticles Bearing PF4 and Anti-GAGS Immunoglobulins in Patients with Sepsis

“…Circulating MPs were assayed by flow cytometry (Cytoflex, Beckman Coulter, Pasadena, CA, USA), as described previously [ 3 , 17 ]. Total MPs were identified by their dimensional features using beads of specific diameters with conformational characteristics resembling those of MPs (Megamix SSC-fluorescent beads [0.16, 0.24, 0.5, 0.9 and 3 μm]), and labeling them with monoclonal anti-annexin V conjugated with Fluorescein isothiocyanate (FITC- Bender Med Systems GmbH, Vienna, Austria).…”

Molecular Crosstalk between the Hepatitis C Virus and the Extracellular Matrix in Liver Fibrogenesis and Early Carcinogenesis

“…Extracellular vesicles are nanosized particles shed into body fluids by many cell types that carry various bioactive molecules; among them, plasma microvesicles (100–1000 nm in size) are key messengers of cellular communication. Enhanced microvesicle levels were linked to disease activity and progression, e.g., microvesicles isolated from patients with HCV-related decompensated cirrhosis induce vascular hypocontractility, contributing to portal hypertension and circulatory dysfunctions [ 164 ]. Versican-positive microvesicles were found elevated in patients with HCV-induced cirrhosis, and further increased with HCC [ 103 ].…”

“…Versican-positive microvesicles were found elevated in patients with HCV-induced cirrhosis, and further increased with HCC [ 103 ]. In patients who had received DAAs, the levels of versican-positive microvesicles dropped at the end of treatment and remained low throughout the 48-week follow-up [ 164 ]. This supports the view that DAA-induced eradication of HCV could promote a reversal of fibrosis, and versican-positive microvesicles could be a potential early biomarker of liver fibrosis.…”