Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2020; 26(19): 2416-2426
Published online May 21, 2020. doi: 10.3748/wjg.v26.i19.2416
Gamma-glutamyl transferase and cardiovascular risk in nonalcoholic fatty liver disease: The Gut and Obesity Asia initiative
Panyavee Pitisuttithum, Wah-Kheong Chan, George Boon-Bee Goh, Jian-Gao Fan, Myeong Jun Song, Phunchai Charatcharoenwitthaya, Ajay Duseja, Yock-Young Dan, Kento Imajo, Atsushi Nakajima, Khek-Yu Ho, Khean-Lee Goh, Vincent Wai-Sun Wong, Sombat Treeprasertsuk
Panyavee Pitisuttithum, Sombat Treeprasertsuk, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Wah-Kheong Chan, Khean-Lee Goh, Department of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
George Boon-Bee Goh, Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore 169608, Singapore
Jian-Gao Fan, Department of Gastroenterology, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Myeong Jun Song, Department of Internal Medicine, The Catholic University of Korea, Daejeon 301-723, South Korea
Phunchai Charatcharoenwitthaya, Division of Gastroenterology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Ajay Duseja, Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
Yock-Young Dan, Khek-Yu Ho, Department of Medicine, National University of Singapore 119228, Singapore
Kento Imajo, Atsushi Nakajima, Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
Vincent Wai-Sun Wong, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong 999077, China
Author contributions: Treeprasertsuk S designed the study and revised the manuscript critically for important intellectual content; Pitisuttithum P, Chan WK, Goh GBB, Fan JG, Song MJ, Charatcharoenwitthaya P, Duseja A, Dan YY, Imajo K, Nakajima A, Ho KY, Goh KL, Wong VWS, and Treeprasertsuk S contributed to data acquisition; Pitisuttithum P and Treeprasertsuk S analyzed and interpreted the data; Pitisuttithum P drafted the manuscript; All authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by The Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Informed consent statement: This is a retrospective study and exemption of signed informed consent application had been approved by Ethics Committee. The analysis used anonymous clinical data after each patient agreed to treatment by written consent.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article 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 NonCommercial (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: Sombat Treeprasertsuk, MD, PhD, Professor, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Rama4 Road, Pathumwan District, Bangkok 10330, Thailand. battan5410@gmail.com
Received: January 18, 2020
Peer-review started: January 18, 2020
First decision: February 28, 2020
Revised: April 26, 2020
Accepted: April 29, 2020
Article in press: April 29, 2020
Published online: May 21, 2020
Research background

In general population, gamma-glutamyl transferase (GGT) levels have shown the promising results in cardiovascular disease (CVD) risk prediction. The proposed mechanism of the association between GGT level and CVD risk is GGT function on the metabolism of glutathione, which is an important cellular antioxidant in humans.

Research motivation

GGT activities are reportedly abundant in the liver. In nonalcoholic fatty liver disease (NAFLD) patients, whether GGT levels can predict CVD risk is largely debated. Our study focused on the association of GGT level and CVD risk in NAFLD patients.

Research objectives

We aimed to identify the association of baseline GGT level and the QRISK2 score among patients with biopsy-proven NAFLD.

Research methods

This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia workgroup. Patients with available baseline GGT level and variables for the QRISK2 calculation were included.

Research results

A total of 1122 patients were included in the final analysis. The median 10-year CVD risk (interquartile range [IQR]) was 5.9% (2.6-10.9), and the median relative risk of CVD over 10 years (IQR) was 1.65 (1.13-2.2) compared to healthy individuals with the same age, sex, and ethnicity. Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk (P < 0.001). Median GGT level was not different between the two groups (GGT [U/L]: median [IQR], high risk 60 [37-113] vs low risk 66 [38-103], P = 0.56). There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score (r = 0.02).

Research conclusions

NAFLD patients have higher 10-year-CVD risk than healthy controls. Apart from traditional risk factors, advanced fibrosis is a predictor of high-risk CVD. However, the baseline GGT level and GGT quartile cannot be used to predict CVD risk in patients with established NAFLD.

Research perspectives

To date, CVD risk assessment in NAFLD patients is based on general population risk assessment tools. Including liver fibrosis parameters may assist in identifying NAFLD patients with high-CVD-risk. Prospective studies are needed.