Non-invasive biomarkers for the detection of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents a major global health problem, being the fifth most common cancer and the second most common cause of cancer-related death worldwide. Globally, HCC incidence has increased in the last two decades and is expected to keep growing until 2030. To achieve a decrease in disease-related mortality, current international guidelines recommend surveillance with abdominal ultrasound (US) every six months in the high-risk populations. US shows an acceptable diagnostic accuracy when used as a surveillance test, with specificity >= 90%, but suboptimal sensitivity ranging from 58% to 89%, due to various technical limitations that affect its performance, particularly in the early detection of small HCC nodules. New reliable non-invasive biomarkers are needed to improve the diagnostic accuracy of surveillance programs, thus overcoming the flaws of US examination and leading to the identification of HCC nodules at earlier and more curable stages. Several non-invasive tests for the early diagnosis of HCC have been investigated, including the well-known alpha-fetoprotein (AFP), but so far no one has shown adequate diagnostic accuracy and cost-effectiveness to deserve large-scale introduction in surveillance protocols. Nevertheless, the recent advances in biotechnologies have been essential to boost the research in the field of tumor biomarkers. This review will go through current knowledge and recent literature dealing with old and new HCC diagnostic biomarkers, from traditional AFP to innovative RNA molecules (miRNAs, circRNAs, lncRNAs).