Abstract
Hepatocellular carcinoma (HCC) is a leading cause of global cancer death. Major etiologies of HCC relate to chronic viral infections as well as metabolic conditions. The survival rate of people with HCC is very low and has been attributed to late diagnosis with limited treatment options. Combining ultrasound and the biomarker alpha-fetoprotein (AFP) is currently one of the most widely used screening combinations for HCC. However, the clinical utility of AFP is controversial, and the frequency and operator-dependence of ultrasound lead to a variable degree of sensitivity and specificity across the globe. In this review, we summarize recent developments in the search for non-invasive serum biomarkers for early detection of HCC to improve prognosis and outcome for patients. We focus on tumor-associated protein markers, immune mediators (cytokines and chemokines), and micro-RNAs in serum or circulating extracellular vesicles and examine their potential for clinical application.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy
It is linked to infections with the hepatitis B virus (HBV) or hepatitis C virus (HCV) and alcoholic or nonalcoholic fatty liver disease (NAFLD), which are the most common underlying etiologies [2,3,4]
HCC surveillance comprising of ultrasound screening every six months is recommended for all patients with cirrhosis, but, as mentioned above, tailoring HCC surveillance programs may be necessary for certain diseases (i.e., HBV and NAFLD) so to include at-risk non-cirrhotic patients [9]
Summary
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. According to current epidemiological data, it is the fourth leading cause of cancer mortality worldwide, ranking among the most commonly diagnosed cancer in both genders [1,2]. According to World Health Organization estimates, globally, more than one million patients will die from liver cancer in 2030 [6] These data underscore the magnitude of the HCC-associated disease burden, which, despite the advances made in its surveillance and diagnosis, is still often diagnosed at advanced stages, precluding timely and eventually curative therapeutic intervention resulting in poor prognosis. HCC surveillance comprising of ultrasound screening every six months is recommended for all patients with cirrhosis, but, as mentioned above, tailoring HCC surveillance programs may be necessary for certain diseases (i.e., HBV and NAFLD) so to include at-risk non-cirrhotic patients [9]. We aim to present what are considered to be the most advanced, important or novel biomarkers and not to present an exhaustive review
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