Extracellular Vesicles in Liver Diseases: Diagnostic, Prognostic, and Therapeutic Application

Abstract

Extracellular vesicles, comprising exosomes, microvesicles, and apoptotic bodies, represent an emerging field in disease diagnostics and prognosis. They can be isolated from peripheral blood of patients as well as from other body fluids and can therefore be considered a minimally invasive liquid biopsy screening tool. Especially their surface antigen composition can reveal information about disease backgrounds. For several liver diseases, including fatal hepatocellular and cholangiocellular carcinoma as well as other nonmalignant liver disorders such as nonalcoholic fatty liver disease, alcoholic hepatitis, or acute liver failure, it has been shown that extracellular vesicle (EV) surface profiling can be useful for disease diagnosis and prognosis. This review focuses on latest advances in these areas to improve liver disorder detection and management. Additionally, the authors will discuss possible therapeutic applications of EVs in liver diseases, which might be a potent treatment option in the future.

Extracellular Vesicles in NAFLD/ALD: From Pathobiology to Therapy

“…Regarding the use of EVs as therapeutic agents, most of the available evidence has been generated using mesenchymal stem cell (MSC)-derived EVs obtained from human umbilical cords or human embryos that have been tested in numerous preclinical liver disease models (e.g., carbon tetrachloride, thioacetamide, D-galactosamine/TNF-α-induced lethal hepatic failure, and bile duct ligation) with promising results [11,53]. Data for NAFLD and ALD are more limited and are reviewed in the corresponding sections below.…”

“…A third, and still nascent, approach related to EV-based therapy is based on the concept that interfering with EV secretion or uptake may attenuate harmful effects on target cells [11,64]. In this regard, several pharmacological agents are being explored that have been shown to inhibit EV trafficking, modify lipid metabolism, or decrease EV secretion.…”

“…Recent studies have focused on the role of EVs in ALD [11,14,84,85]. Both hepatocyte-and monocyte-derived EVs have been postulated to regulate macrophage differentiation, thereby promoting inflammation in alcoholic hepatitis (AH) [24,41,55,72,86].…”

“…In the field of hepatology, EVs have recently emerged as novel players in the pathogenesis and progression of several conditions [11][12][13], including the two most common liver diseases worldwide: nonalcoholic liver disease (NAFLD) and alcoholic liver disease (ALD) [14]. Specifically, recent studies point to a significant role of EVs in modulating injury, amplifying inflammation, and promoting liver fibrosis in both NAFLD and ALD [15][16][17].…”

Extracellular Vesicles, A Possible Theranostic Platform Strategy for Hepatocellular Carcinoma—An Overview

“…Since different stages of liver disease are associated with different EV cargoes, EV profiling has potential diagnostic and prognostic value in HCC [11,34]. Increasing number of reports indicate that EVs also have an important role in liver metastasis from other tumor types, preparing the premetastatic niche to receive metastatic tumor cells, creating a favorable environment for the propagation of metastatic tumor cells [35][36][37]. EVs derived from HCC cells contribute in cell-to-cell communication and have been demonstrated to regulate various cellular processes [38,39].…”