Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2019; 25(36): 5515-5529
Published online Sep 28, 2019. doi: 10.3748/wjg.v25.i36.5515
Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma
Qiang Wang, Qi Chen, Xia Zhang, Xiao-Lan Lu, Qin Du, Tao Zhu, Guo-Yuan Zhang, Dong-Sheng Wang, Qu-Ming Fan
Qiang Wang, Xiao-Lan Lu, Qin Du, Guo-Yuan Zhang, Dong-Sheng Wang, Qu-Ming Fan, Department of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Qiang Wang, Faculty of Laboratory Medicine, Center for Translational Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Qi Chen, Department of Laboratory Medicine, Affiliated Sichuan Ba-Yi Rehabilitation Center of Chengdu University of TCM, Chengdu 610000, Sichuan Province, China
Xia Zhang, Department of Laboratory Medicine of the Ninth People’s Hospital of Chongqing, Chongqing 400700, China
Tao Zhu, Department of Preventive Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Author contributions: All authors contributed to the conceptualisation and design of the study; Wang Q, Chen Q, and Zhang X contributed to the clinical data collection and analysis, and prepared and wrote the first draft of this manuscript; Lu XL, Du Q, and Zhang GY contributed to the clinical data collection; Zhu T contributed to the statistical analysis; Wang DS and Fan QM designed this study and revised the manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Affiliated Hospital of North Sichuan Medical College.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agree to treatment by written consent.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This is an open-access article that 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/
Corresponding author: Qu-Ming Fan, PhD, Research Assistant Professor, Department of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong 637000, Sichuan Province, China. fanqum@163.com
Telephone: +86-817-2190089 Fax: +86-817-2222856
Received: July 25, 2019
Peer-review started: July 25, 2019
First decision: August 17, 2019
Revised: August 25, 2019
Accepted: September 9, 2019
Article in press: September 9, 2019
Published online: September 28, 2019
Abstract
BACKGROUND

Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC.

AIM

To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC.

METHODS

Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC.

RESULTS

Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively; P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively.

CONCLUSION

The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

Keywords: Gamma-glutamyltransferase, Aspartate aminotransferase, Protein induced by vitamin K absence or antagonist II, Alpha-fetoprotein, Hepatitis B virus, Hepatocellular carcinoma

Core tip: This study showed that the ratio of gamma-glutamyltransferase to aspartate aminotransferase (γ-GT/AST ratio) was not correlated with tumour size in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and there was no difference in the AUROC between early-stage HBV-related HCC and HBV-related HCC, indicating that the γ-GT/AST ratio may be more useful than protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in the diagnosis of early-stage HBV-related HCC. PIVKA-II and AFP combined with the γ-GT/AST ratio can enhance the diagnostic value of these biomarkers in different categories of HBV-related HCC.