Pathogenesis of Viral Hepatitis-Induced Chronic Liver Disease: Role of Extracellular Vesicles

Abstract

Extracellular vesicles are encapsulated lipid nanoparticles secreted by a variety of cell types in living organisms. They are known to carry proteins, metabolites, nucleic acids, and lipids as their cargoes and are important mediators of intercellular communication. The role of extracellular vesicles in chronic liver disease has been reported. Chronic liver disease such as viral hepatitis accounts for a significant mortality and morbidity burden worldwide. Hepatic fibrosis has been commonly associated with the chronic form of viral hepatitis, which results in end-stage liver disease, including cirrhosis, liver failure, and carcinoma in some patients. In this review, we discuss the potential role of extracellular vesicles in mediating communication between infectious agents (hepatitis B and C viruses) and host cells, and how these complex cell-cell interactions may facilitate the development of chronic liver disease. We will further discuss how understanding their biological mechanism of action might be beneficial for developing therapeutic strategies to treat chronic liver disease.

Keywords: biomarker; chronic liver disease; extracellular vesicles; hepatic fibrosis; therapy.

Figure 1

Schematic representation of the liver and the single end of its lobule. The portal triad comprising the hepatic artery, bile duct, and portal vein sits at each end of the hepatic lobule. Blood collected from the portal vein and hepatic artery flows toward the central vein through the hepatic sinusoids lined by liver sinusoidal endothelial cells (LSEC) and hepatocytes. The hepatocytes and LSECs are separated by the perisinusoidal space, also known as space of Dissé where hepatic stellate cells (HSC) are located. The hepatocytes produce bile which empties into the bile duct lined by cholangiocytes. The canal of Hering is positioned in the junctional region between cholangiocytes and hepatocytes, where liver progenitor cells (LPC) are proposed to originate.

Figure 2

The role of extracellular vesicles (EVs) in viral-associated liver disease. EVs containing nucleic acids, proteins, or metabolites are involved in the disease progression of viral hepatitis and HCC via various mechanisms, including differentiation of hepatic stellate cells, proliferation and migration of tumor cells, immune suppression and evasion, inflammation and antiviral properties, and transmission of virions. EVs can also be used in the diagnosis and treatment of viral-associated liver disease.