Extracellular vesicles in fatty liver disease and steatohepatitis: Role as biomarkers and therapeutic targets

Non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) are characterized by lipid deposition in hepatocytes in the absence or presence of excessive alcohol consumption, respectively, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) or alcoholic hepatitis (AH) and from mild fibrosis to cirrhosis. Fatty liver disease and steatohepatitis similarly occur in individuals who have both metabolic syndrome and excessive alcohol intake; therefore, the single overarching term metabolic associated fatty liver disease (MAFLD) has been proposed to better reflect these risk factors and the continuity of disease progression. Extracellular vesicles (EVs) are membrane-bound endogenous nanoparticles released into the extracellular space by a majority of cell types. Liver disease-related EVs contain a variety of cellular cargo and are internalized into target cells resulting in the transfer of bioinformation reflecting the state of the donor cell to the recipient. Furthermore, EV composition can be used to identify the degree and type of liver disease, suggesting that EV composition may be a useful biomarker. With regard to MAFLD, the presence of metabolic risk factors, such as insulin resistance, will be indicated by adipose tissue-derived EVs and with that comes the potential to use as a clinical monitor of overall metabolic status. However, the inhibition of specific EV composition may be difficult to implement as a real-world therapeutic approach. Current global evidence shows that mesenchymal stem cell (MSCs)-derived EVs (MSC-EVs) play an important role in regulating the immune response, which has spawned a clinical trial to treat liver disease.