Circulating microRNAs for early detection of hepatitis B-related hepatocellular carcinoma.

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Hepatocellular carcinoma (HCC) is a major challenge for global health. Indeed, HCC represents the third leading and fastest rising cause of cancer death worldwide (1). About 90% of HCC cases can be associated with a well-characterized underlying risk factor including chronic hepatitis B, hepatitis C, ethanol consumption, aflatoxin exposure, non-alcoholic fatty liver disease, metabolic diseases like diabetes, and hereditary liver disease (1-3). Although the risk of developing HCC can be reduced in patients by treatment of the underlying cause, e.g., by viral clearance, strategies to prevent cancer development in patients with advanced fibrosis and established cirrhosis are still lacking (4). Furthermore, despite the recent improvements, treatment options for HCC remain largely unsatisfactory (5). Early diagnosis through surveillance of at-risk patients increases the chance of effective therapy. Clinical practice guidelines recommend periodic ultrasound-based surveillance of patients with cirrhosis (6). However, ultrasound detection of small liver tumors can be challenging and depends on the expertise of the operator. Therefore, several non-invasive biomarkers have been assessed for their utility in determining HCC risk and/or detecting HCC at early stages. Alpha-fetoprotein (AFP) is the most widely used diagnostic serum marker for HCC. However, since its diagnostic and predictive value is largely limited by the presence of AFP-negative HCC as well as the impact of the underlying liver disease (2,6), its use for HCC surveillance is currently not recommended by American and European guidelines. Thus there is an unmet need for novel serum biomarkers for HCC diagnosis capable of increasing the diagnostic and predictive power in surveillance programs.