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

Abstract

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.

miR-361-3p Regulates Liver Tumor-initiating Cells Expansion and Chemo-resistance

“…Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world, accounting for 90% of human liver cancer (21). The incidence of liver cancer is rising due to various factors such as hepatitis, alcoholic fatty liver, nonalcoholic fatty liver and a atoxin (22,23). Hepatectomy and liver transplantation are commonly used in patients with early stage HCC (24).…”

Risk Factors and Biomarkers for Chronic Hepatitis B Associated Hepatocellular Carcinoma

“…Extracellular vesicles (EVs) are a heterogeneous group of membranous “cargo” vesicles comprised of proteins, lipids, RNA, and miRNA packaged within a lipid bilayer. They are released into the extracellular environment from healthy, inflamed, malignant, or dying apoptotic cells [ 117 , 118 , 119 ]. EVs are classified based on their biogenesis and size per minimal information for studies of extracellular vesicles (MISEV) 2018 guidelines into small EVs (also called exosomes, with sizes <100 nm or <200 nm) and large EVs (also called microvesicles (MVs), with sizes >200 nm) [ 120 ].…”

“…They are released into the extracellular environment and can be detected in the serum, plasma, urine, saliva, etc. [ 117 ]. Moreover, they are protected from degradation by the lipid bilayer, increasing their resistance to RNases, making them an attractive noninvasive liquid biomarker to provide a snapshot of their cells of origin [ 117 , 123 , 124 ].…”

“…[ 117 ]. Moreover, they are protected from degradation by the lipid bilayer, increasing their resistance to RNases, making them an attractive noninvasive liquid biomarker to provide a snapshot of their cells of origin [ 117 , 123 , 124 ]. Once released into the extracellular environment, they serve as intercellular communication portals via direct receptor activation or indirectly via internalization into target cells.…”

Relevance of platelet-derived microvesicles in cirrhosis: The debate remains open

“…We read with great interest the review by Thietart and Rautou on extracellular microvesicles in liver diseases. 1 They accurately describe the remaining challenges regarding both technical aspects and the relevance of microvesicle assessment for diagnostic and prognostic purposes. However, a couple of points deserve specific comment.…”