Frequently Abnormal Serum Gamma-glutamyl Transferase Activity is Associated with Future Development of Fatty Liver: a Retrospective Cohort Study

Overview

Journal BMC Gastroenterol

Publisher Biomed Central

Specialty Gastroenterology

Date 2020 Jul 12

PMID 32650722

Citations 19

Authors

Hideki Fujii

Haruna Doi

Tetsuhisa Ko

Taito Fukuma

Toru Kadono

Kohei Asaeda

Reo Kobayashi

Takahiro Nakano

Toshifumi Doi

Yoshikazu Nakatsugawa

Shinya Yamada

Takeshi Nishimura

Naoya Tomatsuri

Hideki Sato

Yusuke Okuyama

Hiroyuki Kimura

Etsuko Kishimoto

Nami Nakabe

Takatomo Shima

Affiliations

Soon will be listed here.

Abstract

Background: Nonalcoholic fatty liver disease is characterized by excessive hepatic fat accumulation. Some individuals frequently present elevated gamma-glutamyl transferase (GGT) levels without fatty liver ultrasound images and other abnormal liver enzymes levels. However, whether these individuals are at an elevated risk for developing fatty liver is unclear. We compared fatty liver change rates and risk factors between individuals with frequently elevated GGT levels and those with normal levels.

Methods: We designed a retrospective cohort study on the basis of complete medical checkup records. One group of individuals had presented normal serum GGT levels during the observation period (Normal-GGT group, n = 2713). Another group had had abnormal elevated serum GGT levels frequently (Abnormal-GGT group, n = 264). We determined the fatty liver change incident rates before and after propensity score matching. We explored confounding factors affecting fatty changes in each group using univariate and multivariate Cox models.

Results: The change incidence rates were 5.80/1000 and 10.02/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively. After propensity score matching, the incidence rates were 3.08/1000 and 10.18/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively (p = 0.026). The factors associated with fatty liver changes in the Normal-GGT group included body mass index (BMI), hemoglobin, alanine aminotransferase (ALT), albumin, triglyceride (TG), fasting blood sugar, and high-density lipoprotein levels. Those in the Abnormal-GGT group were platelet counts and TG. In our multivariable analysis, BMI, ALT, albumin, and TG levels were independent predictors of fatty changes in the Normal-GGT group, and high TG level was the only independent predictor in the Abnormal-GGT group.

Conclusions: The incidence rate of fatty liver change in the Abnormal-GGT group was higher than that in the Normal-GGT group. Consecutive elevated GGT levels increase the risk for fatty liver, and high TG levels in those individuals further independently increase the risk.

Citing Articles

Investigating the prevalence and associated factors of elevated liver enzymes and dyslipidemia during pregnancy.

Mou A, Ali N Sci Rep. 2025; 15(1):3967.

PMID: 39893319 PMC: 11787354. DOI: 10.1038/s41598-025-88798-4.

BMI gain and dietary characteristics are risk factors of MASLD in non-obese individuals.

Taniguchi H, Ueda M, Kobayashi Y, Shima T Sci Rep. 2025; 15(1):2606.

PMID: 39838114 PMC: 11751101. DOI: 10.1038/s41598-025-86424-x.

Elevated GGT to HDL ratio as a marker for the risk of NAFLD and liver fibrosis.

Xuan Y, He F, Liu Q, Dai D, Wu D, Shi Y Sci Rep. 2025; 15(1):10.

PMID: 39748013 PMC: 11695851. DOI: 10.1038/s41598-024-84649-w.

Can Serum Gamma-Glutamyl Transferase Predict All-Cause Mortality in Hypertensive Patients?.

Kawamoto R, Kikuchi A, Ninomiya D Cureus. 2024; 16(8):e68247.

PMID: 39347158 PMC: 11439506. DOI: 10.7759/cureus.68247.

Use of Machine Learning to Predict Onset of NAFLD in an All-Comers Cohort-Development and Validation in 2 Large Asian Cohorts.

Lim D, Chung G, Cher P, Chockalingam Jr R, Kim W, Tan C Gastro Hep Adv. 2024; 3(7):1005-1011.

PMID: 39309369 PMC: 11415843. DOI: 10.1016/j.gastha.2024.06.007.

References

Haring R, Wallaschofski H, Nauck M, Dorr M, Baumeister S, Volzke H . Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels. Hepatology. 2009; 50(5):1403-11. DOI: 10.1002/hep.23135. View

Fukuda Y, Hashimoto Y, Hamaguchi M, Fukuda T, Nakamura N, Ohbora A . Triglycerides to high-density lipoprotein cholesterol ratio is an independent predictor of incident fatty liver; a population-based cohort study. Liver Int. 2015; 36(5):713-20. DOI: 10.1111/liv.12977. View

Shen Z, Xing J, Wang Q, Faheem A, Ji X, Li J . Association between serum γ-glutamyltransferase and chronic kidney disease in urban Han Chinese: a prospective cohort study. Int Urol Nephrol. 2016; 49(2):303-312. DOI: 10.1007/s11255-016-1429-2. View

Liu C . Prevalence and risk factors for non-alcoholic fatty liver disease in Asian people who are not obese. J Gastroenterol Hepatol. 2012; 27(10):1555-60. DOI: 10.1111/j.1440-1746.2012.07222.x. View

Whitfield J . Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001; 38(4):263-355. DOI: 10.1080/20014091084227. View

Hsueh W, Quinones M . Role of endothelial dysfunction in insulin resistance. Am J Cardiol. 2003; 92(4A):10J-17J. DOI: 10.1016/s0002-9149(03)00611-8. View

Lim J, Yang J, Chun B, Kam S, Jacobs Jr D, Lee D . Is serum gamma-glutamyltransferase inversely associated with serum antioxidants as a marker of oxidative stress?. Free Radic Biol Med. 2004; 37(7):1018-23. DOI: 10.1016/j.freeradbiomed.2004.06.032. View

Speliotes E, Massaro J, Hoffmann U, Vasan R, Meigs J, Sahani D . Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: the Framingham Heart Study. Hepatology. 2010; 51(6):1979-87. PMC: 3023160. DOI: 10.1002/hep.23593. View

Sberna A, Bouillet B, Rouland A, Brindisi M, Nguyen A, Mouillot T . European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) clinical practice recommendations for the management of non-alcoholic fatty liver.... Diabet Med. 2017; 35(3):368-375. DOI: 10.1111/dme.13565. View

10.

Perumpail B, Khan M, Yoo E, Cholankeril G, Kim D, Ahmed A . Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol. 2018; 23(47):8263-8276. PMC: 5743497. DOI: 10.3748/wjg.v23.i47.8263. View

11.

Donnelly K, Smith C, Schwarzenberg S, Jessurun J, Boldt M, Parks E . Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005; 115(5):1343-51. PMC: 1087172. DOI: 10.1172/JCI23621. View

12.

RUTTENBURG A, GOLDBARG J, PINEDA E . SERUM GAMMA-GLUTAMYL TRANSPEPTIDASE ACTIVITY IN HEPATOBILIARY PANCREATIC DISEASE. Gastroenterology. 1963; 45:43-8. View

13.

Zelber-Sagi S, Salomone F, Yeshua H, Lotan R, Webb M, Halpern Z . Non-high-density lipoprotein cholesterol independently predicts new onset of non-alcoholic fatty liver disease. Liver Int. 2013; 34(6):e128-35. DOI: 10.1111/liv.12318. View

14.

Tomizawa M, Kawanabe Y, Shinozaki F, Sato S, Motoyoshi Y, Sugiyama T . Triglyceride is strongly associated with nonalcoholic fatty liver disease among markers of hyperlipidemia and diabetes. Biomed Rep. 2014; 2(5):633-636. PMC: 4106613. DOI: 10.3892/br.2014.309. View

15.

Sanyal A, Mirshahi F, Rizzo W, Contos M, Sterling R, Luketic V . Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001; 120(5):1183-92. DOI: 10.1053/gast.2001.23256. View

16.

Angulo P . Nonalcoholic fatty liver disease. N Engl J Med. 2002; 346(16):1221-31. DOI: 10.1056/NEJMra011775. View

17.

Fan J, Kim S, Wong V . New trends on obesity and NAFLD in Asia. J Hepatol. 2017; 67(4):862-873. DOI: 10.1016/j.jhep.2017.06.003. View

18.

Osaki Y, Kinjo A, Higuchi S, Matsumoto H, Yuzuriha T, Horie Y . Prevalence and Trends in Alcohol Dependence and Alcohol Use Disorders in Japanese Adults; Results from Periodical Nationwide Surveys. Alcohol Alcohol. 2016; 51(4):465-73. DOI: 10.1093/alcalc/agw002. View

19.

. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016; 64(6):1388-402. DOI: 10.1016/j.jhep.2015.11.004. View

20.

Lee D, Blomhoff R, Jacobs Jr D . Is serum gamma glutamyltransferase a marker of oxidative stress?. Free Radic Res. 2004; 38(6):535-9. DOI: 10.1080/10715760410001694026. View