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Hepat Oncol. 2017 Oct;4(4):111-122. doi: 10.2217/hep-2017-0019. Epub 2017 Nov 17.

Biomarker development for hepatocellular carcinoma early detection: current and future perspectives.

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Department of Internal Medicine, Division of Gastroenterology & Hepatology, University of Michigan, Ann Arbor, MI 48109, USA.


Early detection of hepatocellular carcinoma (HCC) leads to improved survival; however, current early detection strategies for HCC surveillance are ineffective. Thus, there has been interest in developing biomarkers to aid in the early detection HCC. In this review, we discuss the five phases of biomarker discovery that are necessary for clinical implementation. We also describe the most promising investigational biomarkers and their phase of discovery. We review several promising technologies for the early detection of HCC, including miRNA, metabolomics and proteomics. Promisingly, there are samples from multiple longitudinal cohorts of patients with cirrhosis in the USA that are being collected in order to validate candidate biomarkers for HCC. A biomarker-based strategy has the potential to become the primary surveillance method for HCC detection.


AFP; AFP-L3; DCP; Dickkopf-1; cell-free DNA; glypican-3; metabolomics; midkine; osteopontin; proteomics

Conflict of interest statement

Financial & competing interests disclosure Outside this work, N Parikh has the following declarations: Advisory Board, Eisai Pharmaceuticals, Bayer Pharmaceuticals; Consulting: Bristol Myers Squibb; Research grants: Target Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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