Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 28, 2016; 8(36): 1610-1616
Published online Dec 28, 2016. doi: 10.4254/wjh.v8.i36.1610
Fractionation of gamma-glutamyltransferase in patients with nonalcoholic fatty liver disease and alcoholic liver disease
Shigeo Sueyoshi, Setsu Sawai, Mamoru Satoh, Masanori Seimiya, Kazuyuki Sogawa, Atsushi Fukumura, Mikihiro Tsutsumi, Fumio Nomura
Shigeo Sueyoshi, Setsu Sawai, Masanori Seimiya, Kazuyuki Sogawa, Fumio Nomura, Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan
Mamoru Satoh, Fumio Nomura, Clinical Proteomics Research Center, Chiba University Hospital, Chuo-ku, Chiba 260-8670, Japan
Atsushi Fukumura, Mikihiro Tsutsumi, Department of Hepatology, Kanazawa Medical University, Kahoku, Ishikawa 920-0293, Japan
Author contributions: Sueyoshi S, Sawai S, Satoh M, Seimiya M, Sogawa K, Fukumura A, Tsutsumi M and Nomura F designed research; Sueyoshi S and Satoh M performed research, contributed new analytic tools and analyzed data; Nomura F wrote the paper.
Institutional review board statement: All routine liver biopsy specimens and blood samples from the patients were taken after informed consent and ethical permission was obtained for participation in the study.
Conflict-of-interest statement: The authors declare that they have no competing interest.
Data sharing statement: No additional data are available.
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:
Correspondence to: Fumio Nomura, MD, Professor, Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Telephone: +81-43-2262324 Fax: +81-43-2262324
Received: June 21, 2016
Peer-review started: June 23, 2016
First decision: August 10, 2016
Revised: September 13, 2016
Accepted: November 1, 2016
Article in press: November 2, 2016
Published online: December 28, 2016

To assess how serum gamma-glutamyltransferase (GGT) fractions vary in patients with alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD).


Serum samples were obtained from 14 patients with biopsy-proven alcoholic liver diseases and 9 patients with biopsy proven non-alcoholic fatty liver disease. In addition to these biopsy-proven cases, 16 obese (body mass index > 25) patients without any history of alcohol consumption but with a fatty liver on ultrasound examination and with elevated GGT were included for an additional analysis. Serum GGT fractionation was conducted by high-performance gel filtration liquid chromatography and was separated into the four fractions, big-GGT, medium-GGT, small-GGT (s-GGT), and free-GGT (f-GGT).


The results were expressed as a ratio of each fraction including the total GGT (t-GGT). The s-GGT/t-GGT ratios were lowest for the control group and highest for the ALD group. The differences between the control and NAFLD groups and also between the NAFLD and ALD groups were statistically significant. In contrast, the f-GGT/t-GGT ratios were highest in the control group and lowest in the ALD group, with the differences being statistically significant. As a result, the s-GGT/f-GGT ratios were markedly increased in the NAFLD group as compared with the control group. The increase of the s-GGT/t-GGT ratios, the decrease of the f-GGT/t-GGT ratios, and the increase of s-GGT/F-GGT ratios as compared with the control group subjects were also found in obese patients with clinically diagnosed fatty change of the liver.


Serum GGT fractionation by high-performance gel filtration liquid chromatography is potentially useful for the differential diagnosis of ALD and NAFLD.

Keywords: Gamma-glutamyltransferase, f-GGT/t-GGT ratios, Alcoholic liver disease, Non-alcoholic fatty liver disease, Gel filtration liquid chromatography

Core tip: The aim of this study was to assess whether fractionation of serum gamma-glutamyltransferase (GGT) into four fractions by high-performance gel filtration chromatography is useful for the differential diagnosis of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). In patients with ALD, small-GGT (s-GGT)/total GGT (t-GGT) ratios were significantly higher and free-GGT (f-GGT)/t-GGT ratios were lower than in those in NAFLD. Consequently, there were marked differences in the s-GGT/f-GGT ratio between ALD and NAFLD. These preliminary results indicate that a large-scale study to clarify the diagnostic values of serum GGT fractionation in the differential diagnosis of ALD and NAFLD is warranted.