Elevated Serum Gamma-glutamyl Transferase Levels Research Articles

Study of serum gamma glutamyl transferase in acute stroke - a single centre experience

Background: Gamma-glutamyl transferase (GGT) is an enzyme involved in oxidative stress and inflammation, which are key mechanisms in the pathogenesis of stroke. Recent evidence suggests serum GGT levels may be associated with the risk and prognosis of acute ischemic stroke. This study aimed to investigate serum GGT levels in patients with acute stroke at a single center in India. Methods: This case-control study included 100 patients (50 with acute stroke and 50 age and sex-matched controls). Patients aged 40 to 80 years and diagnosed with acute stroke (encompassing first-time occurrences of intracerebral hemorrhage, ischemic stroke, and subarachnoid hemorrhage) were included in the study. Serum GGT levels were compared between stroke patients and controls. The association of GGT with various risk factors was also analyzed among cases. Results: The mean age of cases is 60.2±10.07 years. Hemorrhagic stroke was most common and found in 52% of cases. Mean serum GGT levels were significantly higher in stroke patients (55.2540±40.8909 U/l). Higher serum GGT levels were associated with male gender, presence of diabetes, hypertension, dyslipidemia and smoking and were found to be statistically significant (p<0.005). Age and stroke type were found to be not significantly associated with GGT levels. Conclusions: In conclusion, our study findings indicate that elevated serum GGT levels are associated with an increased risk of stroke, particularly in male patients and those with hypertension, dyslipidemia, and diabetes. Further prospective studies are needed to establish the predictive value of GGT for stroke.

Serum gamma glutamyl transferase levels in metabolic syndrome in obese south Indian population

Background: Increased waist circumference in metabolic syndrome (MS), which reflects central obesity is associated with an increased risk of type 2 diabetes, dyslipidemia, hypertension and coronary vascular disease. Generation of free radicals in central obesity depletes intracellular glutathione, thereby induces release of gamma glutamyl transferase (GGT) into circulation. Elevated GGT levels could be a marker of high oxidative stress which is known to be associated with central obesity and metabolic syndrome. Hence the aim of this study was to determine the association of GGT levels with components of metabolic syndrome in obese South Indian population. Materials and methods: In this case control study conducted at Master Health Check (MHC) Department, Sri Ramachandra Medical College, study population included 60 obese subjects with metabolic syndrome (cases) and 60 non obese subjects (controls) of South Indian population who were non-smokers and non-alcoholics, between the ages of 30-50 years. Components of metabolic syndrome such as waist circumference, blood pressure, fasting plasma glucose, lipid profiles and GGT measured in both the groups. Data between cases and controls compared with unpaired student t-test. Pearson’s correlation was performed to find the association of GGT levels with other variables in Metabolic syndrome. Results: Serum GGT levels were significantly higher in metabolic syndrome patients (cases) than controls with p < 0.0001. High levels of serum GGT were also associated with increase in BP and atherogenic lipid levels and ratios. Conclusion: Elevated serum GGT levels were significantly associated with components of metabolic syndrome in obese South Indian population.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

BackgroundA high prevalence of diabetes mellitus (DM) coexisting with autoimmune pancreatitis (AIP) is observed. However, evidence on the circumstances under which corticosteroid therapy (CST) for AIP improves or worsens DM is scarce. This study aimed to demonstrate and identify predictors of DM control under the influence of CST. MethodsPatients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed: pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM). The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as ‘improvement’ and ‘non-improvement’ (including ‘no change’ and ‘exacerbation’). ResultsAmong 101 patients with type 1 AIP, 52 (51.5%) patients were complicated with DM at the time of AIP diagnosis, with 36 patients in the cDM group and 16 patients in the pDM group. The incidences of diffuse pancreatic swelling (72.2%) and pancreatic body/tail involvement (91.7%) were significantly higher in the cDM group than in both the pDM and nDM groups. Of the 52 patients with DM, CST was administered in 48 cases. Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase (GGT) level at AIP diagnosis [odds ratio (OR) = 0.032, 95% confidence interval (CI): 0.003-0.412, P = 0.008] and pancreatic atrophy after CST (OR = 0.027, 95% CI: 0.003-0.295, P = 0.003) were negatively associated with DM control improvement. ConclusionsPatients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis. CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis, particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Serum Gamma-Glutamyltransferase Levels Predict the Development of Cerebral Infarction in the Korean Population.

PurposeThis study examined the relationship between serum gamma-glutamyltransferase concentration and the risk of cerebral infarction in the Koreans.Materials and MethodsA total of 209,481 out of 223,551 participants in the National Health Information Database who received medical checkups in 2009 were included in the final analysis. The diagnosis code ICD I63 was used for identifying cerebral infarction cases and tracked the development of cerebral infarction by 2013. Cox proportional hazards model was used to calculate hazard ratios (HRs) for cerebral infarction and their confidence interval (CI).ResultsDuring a follow-up period of 915,387.5 person-years, 2403 incident cases of cerebral infarction developed between 2009 and 2013. After adjusting for multiple covariates, the hazard ratios (95% confidence interval) for incident cerebral infarction, comparing the second, third, and fourth quartile of serum gamma-glutamyltransferase levels with the first quartile, were 1.11 (0.98–1.27), 1.39 (1.22–1.58), and 1.49 (1.29–1.71), respectively (P for trend <0.001).ConclusionElevated serum gamma-glutamyltransferase levels were independently associated with the future development of cerebral infarction in Koreans.

Enhanced Susceptibility to Breast Cancer in Korean Women With Elevated Serum Gamma-Glutamyltransferase Levels: A Nationwide Population-Based Cohort Study.

BackgroundThe incidence of breast cancer has been gradually increasing in Korea. Recently, the elevated level of serum gamma-glutamyltransferase (GGT) has emerged to be associated with the development and progression of some malignancies. This study aimed to determine the effect of serum GGT levels on the risk of developing breast cancer in Korean women.MethodsWe used National Health Insurance Service Health Checkup data to examine the association between serum GGT levels and breast cancer development in Korean women. Women aged 40 years or older who participated in the Korean National Health Screening Examination between January 2009 and December 2009 and who did not develop any cancer within 1-year post examination were included in this analysis (n = 3,109,506). Cox proportional hazard regression analysis was conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsOverall, an elevated serum GGT level was associated with the increased risk of developing breast cancer; compared to the Q1 group, the Q4 group showed a significantly increased breast cancer risk (HR: 1.120,95% CI: 1.08–1.162). Such a relationship was stronger in post-menopausal women than pre-menopausal women (HR: 1.173, 95% CI: 1.107–1.243; HR: 1.070, 95% CI:1.019–1.124). Women with a high GGT level (Q4) were also at an increased risk of developing carcinoma in situ (CIS) (HR: 1.114, 95% CI: 1.04–1.192). In post-menopausal women, the Q4 group also exhibited higher CIS risk (HR: 1.266, 95% CI: 1.132–1.416). However, no significant difference in the risk of developing CIS was observed between the Q1 and Q4 groups in pre-menopausal women. Further analysis revealed that obese, post-menopausal women with a high GGT level (Q4) were associated with an increased risk of developing breast cancer (HR: 1.214, 95% CI: 1.125–1.31) and CIS (HR: 1.348, 95% CI: 1.159–1.569).ConclusionsOur study results demonstrate that increased serum GGT level is a risk factor for developing breast cancer. The post-menopausal women group with obesity and elevated serum GGT level showed the highest incidence of breast cancer. Thus, serum GGT concentration could be a novel and potential risk factor for breast cancer. Further validation in different ethnic groups would be warranted.

Frequently abnormal serum gamma-glutamyl transferase activity is associated with future development of fatty liver: a retrospective cohort study

BackgroundNonalcoholic 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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.

Inflammatory Bowel Disease in Children with Elevated Serum Gamma Glutamyltransferase Levels

To assess the characteristics of inflammatory bowel disease and disease prognosis among children with elevated gamma glutamyltransferase (GGT) and primary sclerosing cholangitis (PSC)-ulcerative colitis (UC). Our longitudinal, population-based cohort comprised all children and young adults diagnosed with UC in the Canadian province of Manitoba between 2011 and 2018. Diagnosis of PSC was confirmed based on a combination of cholestatic biochemical markers and cholangiographic features. The Fisher exact test with Bonferroni correction was used to examine the relationship between categorical variables. We enrolled 95 children with UC/Inflammatory bowel disease-unclassified with a median age at diagnosis of 14years (IQR: 10.4-15.9years) and 1399 person-years follow-up. Among them, 9 children developed PSC-UC, with an incidence rate of 6.43 new cases per 1000 person-years. In this cohort, 8 (72.7%) of 11 children with high baseline serum GGT levels developed PSC-UC in comparison with 1 (1.2%) of 84 children with normal serum GGT levels at baseline (P<.001). All children with high serum GGT levels at diagnosis had pancolitis in comparison with 63.9% of children with normal serum GGT levels (P=.01). Children with high serum GGT levels were more likely to be perinuclear neutrophil antibodies-positive than those with normal levels (90.9% vs 52.0%, P=.01). Our findings indicated that pediatric patients with UC and with even mild elevations of serum GGT levels, especially at baseline, might be predisposed to develop PSC.

Serum gamma-glutamyl transferase is a predictor of mortality in patients with acute myocardial infarction.

Gamma-glutamyl transferase (GGT) is involved in the pathogenesis of atherosclerosis and has been associated with adverse cardiovascular outcomes in patients with ischemic heart disease. However, the association between GGT and long-term mortality has not been studied in patients with acute myocardial infarction (AMI).A total of 2239 AMI patients for whom serum GGT values were available and who underwent percutaneous coronary intervention (PCI) were enrolled in the COREA-AMI (CardiOvascular Risk and idEntificAtion of potential high-risk population in Korean patients with AMI) registry. Patients with acute liver injury were excluded. Patients were classified into 2 groups according to normal (n = 1983) or elevated (n = 256) levels of serum GGT. The primary clinical outcome was all-cause mortality. The secondary outcome was cardiac death and recurrent non-fatal myocardial infarction (MI).The median follow-up period was 3.7 years, and both groups had similar characteristics. Patients with elevated GGT had significantly higher all-cause mortality compared to patients with normal GGT (21.9% vs. 14.4%, P = .001). The multivariate Cox proportional hazards model showed that elevated serum GGT level was independently correlated with mortality (hazard ratio 2.12[1.44–3.11]; P < .001). Although elevated serum GGT was independently associated with long-term mortality after 30 days after PCI, there was no association within 30 days after PCI. Elevated GGT was also associated with death of cardiac causes with statistical significance. In the subgroup analysis, stronger associations were observed in the young and female patients and in patients who had ST-segment elevation MI and preserved left ventricular ejection fraction at the first echocardiography after the indexed PCI.Elevated serum GGT is an independent predictor of long-term mortality in AMI patients.

Serum gamma-glutamyl transferase levels affect the prognosis of patients with intrahepatic cholangiocarcinoma who receive postoperative adjuvant transcatheter arterial chemoembolization: A propensity score matching study

BackgroundThe postoperative prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is far from satisfactory. Whether postoperative adjuvant transcatheter arterial chemoembolization (TACE) is effective for patients with ICC after R0 liver resection remains controversial. Materials and methodsWe retrospectively reviewed the data of 272 patients with ICC who received a radical hepatectomy at our center between 2000 and 2011. After the propensity score of postoperative TACE was calculated, 75 patients who received TACE were matched at a 1:2 ratios with 150 patients who did not receive TACE. Univariate and multivariate Cox analyses were performed to identify the independent predictors of overall survival. ResultsThe postoperative protective effect of adjuvant TACE was significantly influenced by serum gamma-glutamyl transferase (GGT) levels (P for interaction = 0.026). Postoperative TACE was not a significant predictor of overall survival (hazard ratio = 0.89, P = 0.704) in patients with GGT levels ≤ 54 U/L. Postoperative TACE was a significant predictor of overall survival in patients with GGT levels >54 U/L (hazard ratio = 0.44, P = 0.001). Regarding short-term outcomes, a total of 74 patients (32.9%) had varying degrees of complications, and the majority of these complications were grade I (18.7%) or II (10.2%). ConclusionThe safety of postoperative TACE was validated, and the results suggest that only patients with elevated serum GGT levels will benefit from this treatment following curative liver resection for ICC.

Serum gamma-glutamyl transferase (GGT) levels within the normal range are associated with a high SVR rate of 85% in treatment-naive patients undergoing Boceprevir triple therapy for HCV genotype 1 (G1) infection in German real-world

Background: A considerable number of patients (pts) with chronic HCV G1 infection will present with elevated serum GGT levels. However, the impact of GGT elevation on virologic response to boceprevir (BOC) triple therapy has not been investigated until now and was therefore the aim of the present interim analysis of the German NOVUS observational study.

Relationships of elevated levels of serum hepatic enzymes and alcohol intake with arterial stiffness in men

Objective: The present study aimed to evaluate the relationships between elevated serum levels of hepatic enzymes and arterial stiffness and to investigate whether alcohol intake had a modifying effect on these relationships in Japanese men. Methods: A total of 647 eligible men aged 35–69 years who underwent measurement of brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness were evaluated. Information on their lifestyle characteristics were obtained from a structured self-administered questionnaire. Serum biochemical factors, including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), were determined. The serum ALT and GGT levels were divided into tertiles, and their associations with baPWV values were evaluated using general linear models adjusted for potential confounding factors. The interaction effects between serum hepatic enzymes and alcohol intake on baPWV were further evaluated. Results: Elevated serum ALT and GGT levels were proportionally associated with increased baPWV after adjusting for the multivariable covariates (P values for trend, 0.004 and 0.003, respectively). Further analyses revealed that the proportional associations between serum levels of hepatic enzymes and baPWV were striking in the subjects without alcohol intake but not in those with alcohol intake. The interaction effect between serum GGT level and alcohol intake on baPWV was significant (P for interaction, 0.042). Conclusion: These results demonstrate that elevated serum ALT and GGT levels are associated with increased arterial stiffness, independent of the classical atherosclerotic risk factors in Japanese men, and that the association of elevated serum GGT level with arterial stiffness differs according to alcohol intake.

Elevated serum gamma-glutamyltransferase levels in patients with dilated ascending aorta

This study aimed to evaluate the serum gamma-glutamyltransferase (GGT) levels as an indirect marker of elevated oxidative stress in patients with dilated ascending aorta. The study was designed as an observational cross-sectional controlled study. One hundred consecutive patients with dilated ascending aorta and 50 consecutive controls with normal ascending aorta diameter were selected for the study by comprehensive transthoracic echocardiography (TTE). The aortic dilatation group was divided into two subgroups, according to the literature as the ectasia group (3.8-4.3 cm, 53 patients, 24 male and 29 female, mean age: 62.9±10.9 years) and the aneurysm group (≥4.4 cm, 47 patients, 18 male and 29 female, mean age: 65.5±11.1 years). The control group consisted of patients demonstrating no ascending aorta dilatation (≤3.7 cm, 50 patients, 24 male and 26 female, mean age: 62.7±9.2 years). ANOVA, Mann-Whitney U test, Pearson's correlation analysis, multivariate logistic regression analysis, and receiver-operator curve analysis were used for statistical analysis. Regarding the comparison of laboratory parameters between the patient and control groups, serum gamma-glutamyltransferase (GGT) levels were found to be statistically significantly higher in both of the aortic dilatation subgroups than in the control group (p<0.001). In the correlation analysis between the ascending aorta diameter and GGT, a statistically significant positive correlation was found (r=0.282, p<0.001). The multivariate regression analysis revealed a significant relationship between GGT and the proximal ascending aorta diameter (β=0.131, odds ratio: 1.140, 95% CI: 1.060-1.225, p<0.001). GGT as a marker of oxidative stress may play a role in the pathogenesis of aneurysm of the ascending aorta.

Postmortem serum levels of amylase and gamma glutamyl transferase (GGT) as markers of systemic tissue damage in forensic autopsy

Serum amylase (AMY) and gamma glutamyl transferase (GGT) are routine clinical markers for investigating pancreatic and hepatobiliary disorders, respectively, but are also increased in systemic deterioration following critical trauma and diseases. The present study investigated the postmortem levels in bilateral cardiac blood of medicolegal autopsy cases without decomposition (n=163), excluding those with pancreatic or hepatic injury, or preexisting pathologies, as well as prolonged death cases, to evaluate the changes due to systemic deterioration in the death process after fatal insults with special regard to intoxication, hyperthermia (heatstroke) and hypothermia (cold exposure). Serum AMY and GGT levels were virtually independent of postmortem interval. Serum AMY level was mostly higher than the clinical reference range, predominantly including salivary fractions, but was usually below 1000U/L except for fatal intoxication, which showed significant increases of total AMY as well as salivary and pancreatic fractions in bilateral cardiac blood. Serum levels of salivary and pancreatic AMY fractions showed tendencies to be related to pancreatic subcapsular and interstitial bleeding, respectively, which were relatively frequent and evident in mechanical asphyxiation, intoxication and hyperthermia (heatstroke). Serum GGT was often elevated (mostly below 300U/L) in cases other than hypothermia (cold exposure). These findings suggest postmortem serum AMY and GGT as indicators of the severity of systemic organ damage in death processes, especially in intoxication; however, elevated serum AMY and GGT levels over 1000 and 300U/L might indicate significant pancreatic and hepatobiliary pathologies, respectively, except for an elevated serum AMY level in intoxication.

Serum Gamma-Glutamyl Transferase Level Is an Independent Predictor of Incident Hypertension in Korean Adults

The aim of our study was to assess the relationship between serum gamma-glutamyl transferase (GGT) level within the normal range and incident hypertension according to drinking and obesity status in nonhypertensive individuals. We followed up 4783 normotensive adults (mean age = 44 years) who had serum GGT levels within the normal range at baseline for 3 years. Subjects were divided into four GGT quartile groups according to their serum GGT level at baseline. The overall incidence of hypertension was 8.1%, and the incidence increased with increasing GGT quartile (3.8%, 6.9%, 9.0%, and 12.4% in the lowest, second, third, and highest GGT quartiles, respectively; P < .001). In the logistic regression analysis adjusted for age, sex, body mass index, lifestyle factors, glucose, uric acid, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, high-sensitivity C-reactive protein, and baseline systolic blood pressure, the odds ratio (ORs) for incident hypertension increased with increasing GGT quartile (P for trend = .030). In the above model, the highest quartile group showed increased ORs compared with those in the lowest quartile group (ORs [95% confidence interval], 2.638 [1.259–5.528]). Subgroup analyses revealed a significant association between GGT quartile and the incidence of hypertension in the drinker and non-overweight groups. Our results indicate that elevated serum GGT levels within the normal range are associated with a higher risk of incident hypertension in Korean adults, particularly, in drinkers and non-overweight individuals, suggesting possible different pathophysiologic mechanisms in the incidence of alcohol- and obesity-related hypertension.

Elevated serum levels of alanine aminotransferase and gamma glutamyltransferase are markers of inflammation and oxidative stress independent of the metabolic syndrome

The present study attempted to establish whether elevated serum levels of alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) are independent (of each other) markers of systemic inflammation and oxidative stress as assessed by the plasma levels of C-reactive protein (CRP) and lipid peroxides (lipOX), regardless of the presence of underlying metabolic syndrome (as defined by the modified Adult Treatment Panel III (ATPIII) criteria). The plasma levels of CRP and lipOX were determined in 1483 middle-age Japanese men (42 ± 9 years). A general linear model analysis indicated that elevated serum ALT and/or serum GGT (levels in the respective highest quartiles) were significantly related to the logarithms of the plasma levels of CRP (Beta = 0.08 (0.05–0.11) and 0.08 (0.05–0.11), respectively) and the logarithm of the plasma levels of lipOX (Beta = 0.03 (0.01–0.05) and 0.03 (0.01–0.05), respectively), regardless of the presence of underlying metabolic syndrome (MetS) ( p < 0.01). In addition, the presence of MetS and elevated serum levels of both of these liver enzymes additively increased the plasma levels of CRP and lipOX. Thus, it is proposed that elevated serum ALT and elevated serum GGT are independent markers of the activation of systemic inflammation and increased oxidative stress, independent of their relationship to MetS, and that the presence of MetS and elevations of both of these liver enzymes may additively worsen the atherogenic state.

Role of gamma-glutamyl transferase activity in patients with chronic hepatitis C virus infection.

Increased serum gamma-glutamyl transferase (GGT) levels are frequently observed in chronic hepatitis C virus (HCV) infection. However, the significance of this finding remains unclear. The purpose of the present paper was to assess the relationship between GGT levels and clinical, biochemical and histological features in chronic HCV-infected carriers. Patients with a liver biopsy presenting anti-HCV and HCV-RNA were evaluated. Age, gender, risk factors of transmission, serum alanine aminotransferase (ALT), GGT and alkaline phosphatase (ALP) levels and histological features were assessed in all. Data were analyzed statistically by the chi2 test and multivariate logistic regression analysis. Among 201 patients studied, elevated GGT levels and bile duct damage were observed in 48% and 35% of them, respectively. No association was seen between GGT level and bile duct damage or between GGT level and hepatic steatosis. Initially, age >40 years (P=0.007), elevated ALT (P=0.01), grading of inflammatory activity (P=0.004) and staging of fibrosis (P<0.001) were found to be associated with elevated GGT levels. After multivariate regression analysis, histology grading 3 and 4 inflammation activity (P=0.01) and staging 3 and 4 fibrosis (P=0.01) remained independently associated with elevated GGT level. A significant number of patients with chronic HCV infection had elevated serum GGT levels. Furthermore, this enzyme seemed to be useful as an indirect marker of more advanced liver disease in chronic hepatitis C.