• hepatocellular carcinoma
• rna expression
• chronic liver disease

Hepatocellular carcinoma (HCC) represents 75%–85% of primary liver cancers1 and is a major global disease, with a high incidence particularly in parts of South-East Asia and sub-Saharan Africa. While the overall incidence is low in countries such as the USA and Australia, risk factors like chronic HBV and HCV infections, autoimmune hepatitis, chronic alcohol abuse and obesity have led to an increased number of cases in recent years.2 Unfortunately, HCC remains a disease with high mortality, despite new therapeutic advances such as liver transplantation or ablation, which can have good outcomes if high-grade dysplastic nodules or small HCCs (<2 cm) are picked up early.3 4 However, the use of serum biomarker α-fetoprotein (AFP) combined with ultrasonography is dependent on the clinical setting and has suboptimal sensitivity for detection of HCC at an early stage.5 AFP also has poor sensitivity in the presence of chronic liver disease (CLD), which means novel biomarkers are needed for the management of at-risk populations.6

The extracellular component of serum and plasma is a rich source of material in the growing field of ‘liquid biopsy’, and extracellular vesicles (EVs) represent a compartment which can readily be isolated and contains lipid, protein and RNA/DNA cargo suitable for biomarker use. Importantly, EVs have also been found to have a wide-range of roles in intercellular communication in health and disease.7 EVs are broadly defined as lipid bilayer structures lacking organelles, which vary in size from 10 nm to 1 µm. EVs include endosomal vesicles formed intraluminally by …