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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2016; 22(37): 8271-8282
Published online Oct 7, 2016. doi: 10.3748/wjg.v22.i37.8271
Circulating predictive and diagnostic biomarkers for hepatitis B virus-associated hepatocellular carcinoma
Stijn Van Hees, Peter Michielsen, Thomas Vanwolleghem
Stijn Van Hees, Peter Michielsen, Thomas Vanwolleghem, Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2650 Edegem, Belgium
Stijn Van Hees, Peter Michielsen, Thomas Vanwolleghem, Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, 2610 Antwerp, Belgium
Author contributions: Van Hees S and Vanwolleghem T conceptualized the manuscript; Van Hees S wrote the manuscript; all authors contributed to the critical revision and editing of the paper; Michielsen P and Vanwolleghem T approved the final version.
Supported by Foundation Against Cancer Belgium, No. 2014-087.
Conflict-of-interest statement: The authors declare no potential conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Thomas Vanwolleghem, MD, PhD, Department of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium. thomas.vanwolleghem@uza.be
Telephone: +32-3-8213853 Fax: +32-3-8214478
Received: April 26, 2016
Peer-review started: April 27, 2016
First decision: June 20, 2016
Revised: July 18, 2016
Accepted: August 5, 2016
Article in press: August 5, 2016
Published online: October 7, 2016
Processing time: 156 Days and 22.4 Hours
Abstract

Chronic hepatitis B virus (HBV) infected patients have an almost 100-fold increased risk to develop hepatocellular carcinoma (HCC). HCC is the fifth most common and third most deadly cancer worldwide. Up to 50% of newly diagnosed HCC cases are attributed to HBV infection. Early detection improves survival and can be achieved through regular screening. Six-monthly abdominal ultrasound, either alone or in combination with alpha-fetoprotein serum levels, has been widely endorsed for this purpose. Both techniques however yield limited diagnostic accuracy, which is not improved when they are combined. Alternative circulating or histological markers to predict or diagnose HCC are therefore urgently needed. Recent advances in systems biology technologies have enabled the identification of several new putative circulating biomarkers. Although results from studies assessing combinations of these biomarkers are promising, evidence for their clinical utility remains low. In addition, most of the studies conducted so far show limitations in design. Attention must be paid for instance to different ethnicities and different etiologies when studying biomarkers for hepatocellular carcinoma. This review provides an overview on the current understandings and recent progress in the field of diagnostic and predictive circulating biomarkers for hepatocellular carcinoma in chronically infected HBV patients and discusses the future prospects.

Keywords: Hepatocellular carcinoma; Hepatitis B virus infection; Biomarkers; Predictive; Diagnostic; Alpha-fetoprotein; Validation; Limitations; MicroRNA

Core tip: Regular screening for hepatocellular carcinoma (HCC) in patients at risk improves their survival rates. Currently available screening methods include abdominal ultrasound and alpha-fetoprotein serum levels, but both methods lack diagnostic accuracy. Recent technological advances have enabled the identification of new predictive and diagnostic hepatitis B virus (HBV)-associated HCC biomarkers. Nevertheless, most of the studies conducted so far show design limitations. This review provides an overview on the current understanding and future prospects of circulating predictive and diagnostic biomarkers for HBV-associated HCC.