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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2016; 22(1): 262-274
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.262
Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma
Pei-Pei Song, Ju-Feng Xia, Yoshinori Inagaki, Kiyoshi Hasegawa, Yoshihiro Sakamoto, Norihiro Kokudo, Wei Tang
Pei-Pei Song, Ju-Feng Xia, Yoshinori Inagaki, Kiyoshi Hasegawa, Yoshihiro Sakamoto, Norihiro Kokudo, Wei Tang, Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo 113-8655, Japan
Author contributions: Kokudo N and Tang W designed the research; Song PP, Xia JF and Inagaki Y conducted the data collection and analysis; Song PP wrote the initial draft of the paper; Hasegawa K and Sakamoto Y revised the paper; all authors were involved in the interpretation of the data and writing the paper; all authors approved the final version of the manuscript and take responsibility for its content.
Supported by Grants-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan.
Conflict-of-interest statement: The authors declare that they have no competing interests.
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: Wei Tang, MD, PhD, Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. tang-sur@h.u-tokyo.ac.jp
Telephone: +81-3-58009269 Fax: +81-3-56843989
Received: May 15, 2015
Peer-review started: May 19, 2015
First decision: July 14, 2015
Revised: July 27, 2015
Accepted: October 13, 2015
Article in press: October 13, 2015
Published online: January 7, 2016
Processing time: 229 Days and 18.4 Hours
Abstract

The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV). According to recommendations by the World Health Organization guidelines for HBV/HCV, alpha-fetoprotein (AFP) testing and abdominal ultrasound should be performed in routine surveillance of HCC every 6 mo for high-risk patients. These examinations have also been recommended worldwide by many other HCC guidelines over the past few decades. In recent years, however, the role of AFP in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by the American Association for the Study of Liver Diseases in 2010, the European Association for the Study of the Liver in 2012, and the National Comprehensive Cancer Network in 2014. Other biomarkers, including the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin, Dickkopf-1, midkine, and microRNA, are being studied in this regard. Furthermore, increasing attention has focused on the clinical utility of biomarkers as pre-treatment predictors for tumor recurrence and as post-treatment monitors. Serum and tissue-based biomarkers and genomics may aid in the diagnosis of HCC, determination of patient prognosis, and selection of appropriate treatment. However, further studies are needed to better characterize the accuracy and potential role of these approaches in clinical practice.

Keywords: Hepatocellular carcinoma; Biomarker; Guideline; Surveillance; Diagnosis; Prognosis

Core tip: Hepatocellular carcinoma (HCC) is a major global health problem due to the high prevalence of the risk factors hepatitis B virus and hepatitis C virus infection. Thus, a good surveillance program and diagnostic strategy for the early detection of HCC should be available. This review summarizes the controversies regarding and perspectives on clinical utility of biomarkers in HCC, especially the current role of alpha-fetoprotein and des-γ-carboxyprothrombin. In addition, research frontiers and prospects for novel biomarkers to evaluate the prognosis for HCC and to facilitate post-treatment monitoring are reviewed.