Retrospective Cohort Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2015; 21(34): 9957-9965
Published online Sep 14, 2015. doi: 10.3748/wjg.v21.i34.9957
Association of serum gamma-glutamyl transferase with treatment outcome in chronic hepatitis B patients
Rui Huang, Chen-Chen Yang, Yong Liu, Juan Xia, Ran Su, Ya-Li Xiong, Gui-Yang Wang, Zhen-Hua Sun, Xiao-Min Yan, Shan Lu, Chao Wu
Rui Huang, Juan Xia, Ran Su, Ya-Li Xiong, Gui-Yang Wang, Zhen-Hua Sun, Xiao-Min Yan, Chao Wu, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
Chen-Chen Yang, Department of Infectious Diseases, Qidong People’s Hospital, Qidong 226200, Jiangsu Province, China
Yong Liu, Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
Shan Lu, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States
Author contributions: Wu C and Lu S designed the research; Huang R, Yang CC, Liu Y, Xia J, Su R, Xiong YL, Wang GY, Sun ZH, and Yan XM performed the research; Huang R and Yang CC analyzed the data; Huang R wrote the paper; all authors have read and approved the final version for submission.
Supported by National Natural Science Foundation of China, No. 81470093; Jiangsu Provincial Outstanding Medical Academic Leader Program, No. LJ201154; and Jiangsu Provincial Clinical Medicine and Technology Special Program, No. BL2012034.
Institutional review board statement: This study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of Nanjing Drum Tower Hospital (Nanjing, China).
Informed consent statement: None.
Conflict-of-interest statement: The authors declare no conflicts of interest associated with the publication of the study.
Data sharing statement: None.
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: Chao Wu, MD, PhD, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, China. dr.wu@nju.edu.cn
Telephone: +86-25-83105890 Fax: +86-25-83307115
Received: March 30, 2015
Peer-review started: March 31, 2015
First decision: May 18, 2015
Revised: June 7, 2015
Accepted: July 8, 2015
Article in press: July 8, 2015
Published online: September 14, 2015
Processing time: 167 Days and 18.3 Hours
Abstract

AIM: To investigate the association of serum gamma-glutamyl transferase (GGT) levels with chronic hepatitis B infection and hepatitis B e antigen (HBeAg) seroconversion.

METHODS: A retrospective study was performed on clinical data collected from patients who had been positive for hepatitis B surface antigen for > 6 mo and who were antiviral-treatment naïve (n = 215) attending the Hepatitis Clinic at Nanjing Drum Tower Hospital between August 2010 and December 2013. Healthy individuals without liver disease (n = 83) were included as controls. Patients were categorized into four groups based on disease status as recommended by the European Association for the Study of the Liver: immune tolerance (IT; n = 47), HBeAg-positive hepatitis (EPH; n = 93), HBeAg-negative hepatitis (ENH; n = 20), and inactive carrier (IC; n = 55). Prediction of complete response (CR) based on serum GGT was also examined in EPH patients (n = 33) treated for 48 wk with nucleos(t)ide analogue (NA) therapy, including lamivudine plus adefovir combination therapy (n = 20) or entecavir monotherapy (n = 13). CR was defined as a serum hepatitis B virus DNA level < 500 copies/mL and HBeAg seroconversion by 48 wk of treatment.

RESULTS: Serum GGT levels were significantly increased in EPH and ENH patients relative to the IT, IC, and healthy control groups (P < 0.01 for all). However, no significant difference in serum GGT levels was found between the EPH and ENH groups. Baseline serum GGT levels were significantly higher in patients who achieved CR (7/33; 21.2%) compared to patients in the non-CR group (26/33; 78.8%; P = 0.011). In addition, the decline in serum GGT was greater in CR patients compared to non-CR patients after 24 wk and 48 wk of treatment (P = 0.012 and P = 0.008, respectively). The receiver operating characteristic curve yielded a sensitivity of 85.71% and a specificity of 61.54% at a threshold value of 0.89 times the upper limit of normal for baseline serum GGT in the prediction of CR following NA therapy.

CONCLUSION: Serum GGT is significantly elevated in EPH and ENH patients and is a potential biomarker for the prediction of HBeAg seroconversion following NA therapy.

Keywords: Gamma-glutamyl transferase; Hepatitis B e antigen; Hepatitis B; Natural history; Nucleos(t)ide analogues; Seroconversion

Core tip: Serum gamma-glutamyl transferase (GGT) levels have been associated with treatment response in chronic hepatitis C patients. However, whether serum GGT levels are associated with chronic hepatitis B infection is unknown. This study provides evidence that serum GGT levels are significantly elevated in patients with hepatitis B e antigen (HBeAg)-positive and HBeAg-negative hepatitis patients. Furthermore, serum GGT levels were investigated as a potential biomarker for the prediction of HBeAg seroconversion in patients with HBeAg-positive hepatitis following a 48-wk course of nucleos(t)ide analogue treatment.