Elevated Gamma-glutamyl Transferase Activity Research Articles

Prevalence of subclinical bactibilia inapparently healthy shelter dogs.

To determine the prevalence of subclinical bactibilia in apparently healthy shelter dogs and characterise serum liver enzymes activities, hepatobiliary histopathology and bile cytology in apparently healthy dogs with and without bactibilia. Healthy, abandoned dogs euthanased for non-medical reasons were prospectively recruited for this cross-sectional study. Whole blood, collected immediately before euthanasia, was submitted for serum liver enzyme activity (alkaline phosphatase, alanine aminotransferase and gamma-glutamyl transferase) analyses. Bile, gall bladder and liver samples were collected aseptically from dogs within 25 minutes of euthanasia. Bile was submitted for bacterial culture and cytology in all dogs. Gall bladder and liver samples were submitted for histopathological examination in bactibilic dogs and nine randomly selected non-bactibilic dogs. Sixty-five healthy dogs were included in this study. Bactibilia was diagnosed in 10.8% (7/65) of dogs, with 9.2% (6/65) of dogs diagnosed on cytological examination and 4.6% (3/65) on culture. Elevated alanine aminotransferase activities were present in one bactibilic and five non-bactibilic dogs; and elevated gamma-glutamyl transferase activities in one bactibilic and two non-bactibilic dogs. No dogs had elevated alkaline phosphatase activities. Histopathological changes in bactibilic and non-bactibilic dogs included lymphoplasmocellular cholecystitis (7/7 and 9/9), gall bladder oedema (7/7 and 9/9), hepatic vacuolar degeneration (6/7 and 8/9), cholangitis (5/7 and 7/9), hepatic nodular hyperplasia (3/7 and 5/9) and hepatic cholestasis (2/7 and 4/9). This study confirms that subclinical bactibilia occurs in a small number of apparently healthy shelter dogs and that subclinical hepatobiliary histopathological abnormalities can occur in apparently healthy bactibilic and non-bactibilic dogs.

Gamma-glutamyl transferase and atrial fibrillation in patients with coronary artery disease

BackgroundThe association between gamma-glutamyl transferase (GGT) and atrial fibrillation (AF) in patients with coronary artery disease (CAD) is uncertain. MethodsThis study included 5501 consecutive patients with CAD, all of whom had baseline GGT measurements available. The primary endpoint was presence of AF. ResultsOverall 809 patients (14.7%) had AF on hospital admission. Patients with AF had significantly higher GGT activity compared with patients in sinus rhythm (median [25th–75th percentile]: 52.0 [32.9–96.0] U/L versus 34.8 [23.8–55.9] U/L, P<0.001). The prevalence of AF increased from 8.6% of patients in the first GGT decile to 30.3% of patients in the tenth decile (P<0.001). After multivariable adjustment, GGT activity remained independently associated with the probability of the presence of AF (adjusted adds ratio=1.66, 95% confidence interval 1.53–1.81, P<0.001 for each standard deviation increment in the GGT logarithmic scale). GGT predicted the probability of AF with an area under the receiver operating characteristic (ROC) curve of 0.6496, 95% confidence interval 0.6287 to 0.6705, P<0.001 indicating moderate strength to discriminate between patients with and without AF. ConclusionsIn patients with CAD, elevated GGT activity is independently associated with the presence of AF. GGT may be a circulating marker of the risk for AF.

Gamma-glutamyl transferase and cardiovascular disease.

Gamma-glutamyl transferase (GGT) is an enzyme located on the external surface of cellular membranes. GGT contributes in maintaining the physiological concentrations of cytoplasmic glutathione and cellular defense against oxidative stress via cleavage of extracellular glutathione and increased availability of amino acids for its intracellular synthesis. Increased GGT activity is a marker of antioxidant inadequacy and increased oxidative stress. Ample evidence suggests that elevated GGT activity is associated with increased risk of cardiovascular disease (CVD) such as coronary heart disease (CHD), stroke, arterial hypertension, heart failure, cardiac arrhythmias and all-cause and CVD-related mortality. The evidence is weaker for an association between elevated GGT activity and acute ischemic events and myocardial infarction. The risk for CVD or CVD-related mortality mediated by GGT may be explained by the close correlation of GGT with conventional CVD risk factors and various comorbidities, particularly non-alcoholic fatty liver disease, alcohol consumption, oxidative stress, metabolic syndrome, insulin resistance and systemic inflammation. The finding of GGT activity in atherosclerotic plaques and correlation of intra-plaque GGT activity with histological indexes of plaque instability may suggest a participation of GGT in the pathophysiology of CVD, particularly atherosclerosis. However, whether GGT has a direct role in the pathophysiology of CVD or it is an epiphenomenon of coexisting CVD risk factors or comorbidities remains unknown and Hill's criteria of causality relationship between GGT and CVD are not fulfilled. The exploration whether GGT provides prognostic information on top of the information provided by known cardiovascular risk factors regarding the CVD or CVD-related outcome and exploration of molecular mechanisms of GGT involvement in the pathophysiology of CVD and eventual use of interventions to reduce circulating GGT activity remain a duty of future studies.

Relation of Gamma-Glutamyl Transferase to Cardiovascular Events in Patients With Acute Coronary Syndromes

The prognostic value of gamma-glutamyl transferase (GGT) in patients with acute coronary syndromes (ACS) has been incompletely investigated. We investigated this clinically relevant question in 2,534 consecutive patients with ACS who underwent percutaneous coronary intervention (PCI). GGT activity was measured before PCI procedure in all patients. Statin therapy at hospital discharge was prescribed in 94% of the patients. The primary outcome was 3-year mortality. Patients were divided into 3 groups: the group with GGT in the first tertile (GGT <28 U/L; n = 848 patients), the group with GGT in the second tertile (GGT 28 to <50 U/L; n = 843 patients), and the group with GGT in the third tertile (GGT ≥50 U/L; n = 843 patients). The primary outcome (all-cause deaths) occurred in 250 patients: 70 deaths (9.7%) among patients of the first, 69 deaths (9.0%) among patients of the second, and 111 deaths (14.8%) among patients of the third GGT tertile (adjusted hazard ratio [HR] 1.24, 95% CI 1.08 to 1.42, p = 0.002) and cardiac and noncardiac deaths occurred in 157 (63%) and 93 patients (37%), respectively. GGT was associated with the increased risk of noncardiac mortality (adjusted HR 1.35 [1.09 to 1.66], p = 0.005) but not cardiac mortality (adjusted HR 1.16 [0.97 to 1.38], p = 0.098; all 3 risk estimates were calculated per SD increase in the logarithmic scale of GGT activity). In conclusion, in contemporary patients with ACS treated with PCI and on statin therapy, elevated GGT activity was associated with the increased risk of all-cause and noncardiac mortality but not with the risk of cardiac mortality.

Predictors of sustained virological response in patients with hepatitis C virus genotype 3 infection.

Aim of the studyTo assess predictors of sustained virological response (SVR) in patients with chronic hepatitis C virus (HCV) genotype 3 treated with standard therapy.Material and methodsWe retrospectively investigated data of 116 consecutive treatment-naïve patients chronically infected with HCV genotype 3, treated with pegylated interferon alpha (PegIFNα) and ribavirin (RBV) for 24 weeks. HCV RNA at week 4 (rapid virological response – RVR) and week 12 (early virological response – EVR) were measured in 85 and 105 patients respectively. Liver biopsy data were available for 103 patients. The variables were compared between patients with an SVR and those without.ResultsOverall 70.7% of patients achieved an SVR. Pretreatment factors including younger age, mild liver fibrosis as well as normal values of gamma-glutamyl transferase (GGT) and platelet count were significantly associated with higher SVR rate in univariate analysis. In the multivariate analysis only baseline platelet count > 140 000/µl and normal GGT activity were correlated with higher SVR rate. At weeks 4 and 12 HCV RNA was undetectable in 34.1% and 84.8% of patients respectively. The SVR rate was significantly higher in patients with an RVR compared to those without (p = 0.002). Only 2 patients with a rapid and early virological response did not achieve an SVR; both had negative pretreatment prognostic factors.ConclusionsIn treatment-naïve patients with genotype 3 HCV infection, low baseline platelet count and elevated GGT activity were significantly associated with poor response to PegIFNα and RBV. Achieving a rapid and early virological response was associated with higher likelihood of an SVR.

Gamma-glutamyl transferase and prognosis in patients with coronary artery disease

BackgroundThe association between gamma-glutamyl transferase (GGT) activity and outcome of patients with coronary artery disease (CAD) remains poorly investigated. MethodsThe study included 5501 patients with CAD treated with percutaneous coronary intervention and GGT measurements available. The primary outcome was 3-year mortality. ResultsGGT activity tertiles were: 1st tertile (GGT<28.10U/L; n=1866), 2nd tertile (GGT≥28.10U/L to49.50U/L; n=1804) and 3rd tertile (GG>49.50U/L; n=1831). There were 110 deaths in the 1st, 111 deaths in the 2nd and 216 deaths in the 3rd GGT tertile (mortality estimates, 7.1%, 7.2% and 13.9%; P<0.001). GGT was independently associated with the increased risk of 3-year all-cause (adjusted hazard ratio [HR]=1.30, 95% confidence interval [CI] 1.18 to 1.44, P<0.001), cardiac (HR=1.21 [1.06–1.39], P=0.005) and non-cardiac (HR=1.42 [1.23–1.63], P<0.001) mortality (all risk estimates calculated per standard deviation increase in the log GGT activity). GGT improved prediction of all-cause (P<0.001) and non-cardiac mortality (P<0.001) but not cardiac mortality (P=0.155). ConclusionsIn patients with CAD, elevated GGT activity is associated with increased risk of 3-year all-cause, cardiac and non-cardiac mortality. GGT provided incremental prognostic information on top of cardiovascular and metabolic risk factors for prediction of all-cause and non-cardiac mortality but not cardiac mortality.

Gamma-glutamyl transferase is associated with sarcopenia and sarcopenic obesity in community-dwelling older adults: results from the Fifth Korea National Health and Nutrition Examination Survey, 2010-2011.

Although elevated serum gamma-glutamyl transferase activity (GGT) has been linked with metabolic risk factors for sarcopenia, including non-alcoholic fatty liver disease, adiposity, and insulin resistance, whether GGT independently associated with sarcopenia and sarcopenic obesity has not yet been investigated. We analyzed cross-sectional data of 3,193 community-dwelling adults (42.2% men, age 63.4 ± 8.7) aged ≥50 years from the Fifth Korean National Health and Nutrition Examination Survey, 2010-2011. Sarcopenia was defined as a calculated value of the appendicular skeletal muscle mass divided by body weight (ASM/Wt, %) <1 standard deviation below the sex-specific mean for healthy young adults. Sarcopenic obesity was defined as sarcopenia combined with a waist circumference ≥90 cm for men and ≥85 cm for women. The prevalence of sarcopenia and sarcopenic obesity increased stepwise from the lowest to highest GGT quintiles (sarcopenia, 20.2-39.7%; sarcopenic obesity, 7.5-27.3%; P for trend, <0.001). Serum GGT activity was associated negatively with ASM and positively with waist circumference. In multivariate logistic regression analyses, participants in the highest GGT quintile had a 2.3-fold increased risk of sarcopenia and 3.4-fold risk of sarcopenic obesity versus those in the lowest quintile, whereas each single-unit increase in natural log-GGT associated independently with a 35% increased risk of sarcopenia and 62% increased risk of sarcopenic obesity after adjusting for age, sex, body mass index, and other confounders. Elevated serum GGT activity was independently associated with sarcopenia and sarcopenic obesity in community-dwelling older adults.

Serum gamma-glutamyl transferase levels and in-hospital mortality in patients with acute heart failure

Acute heart failure (AHF) is a major cause of hospitalisation, morbidity and mortality worldwide. Gamma-glutamyl transferase (GGT) is an enzyme responsible for the extracellular catabolism of antioxidant glutathione and a potential risk indicator of cardiac mortality. Limited data exists on the prognostic value of circulating levels of GGT in patients hospitalized due to AHF. To study the association between baseline GGT activity and in-hospital mortality in AHF patients. The study cohort consisted of 183 AHF patients with left ventricular ejection fraction (LVEF) < 50%. The primary endpoint was in-hospital mortality. Patients were divided into two groups according to in-hospital mortality. The relationship between GGT activity and in-hospital mortality was tested using logistic regression models, adjusting for clinical characteristics and echocardiographic findings. After adjustment for possible confounders, GGT level was significantly related (OR 1.056, 95% CI 1.018-1.096, p = 0.04) to in-hospital mortality. Elevated GGT activity is an independent predictor of short-term mortality in patients with AHF and reduced LVEF.

Predictive Values of Aspartate Aminotransferase and Gamma-Glutamyl Transferase for the Hepatic Accumulation of Copper in Cattle and Buffalo

Ten cattle and 10 buffalo were divided into 2 groups (control [n = 8] and experimental [n = 12] that received daily administration of copper. Three hepatic biopsies and blood samples were performed on days 0, 45, and 105. The concentration of hepatic copper was determined by spectrophotometric atomic absorption, and the activities of aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) were analyzed. Regression analyses were done to verify the possible existing relationship between enzymatic activity and concentration of hepatic copper. Sensitivity, specificity, accuracy, and positive and negative predictive values were determined. The serum activities of AST and GGT had coefficients of determination that were excellent predictive indicators of hepatic copper accumulation in cattle, while only GGT serum activity was predictive of hepatic copper accumulation in buffalo. Elevated serum GGT activity may be indicative of increased concentrations of hepatic copper even in cattle and buffalo that appear to be clinically healthy. Thus, prophylactic measures can be implemented to prevent the onset of a hemolytic crisis that is characteristic of copper intoxication.

Elevated Gamma-Glutamyltransferase Activity and Perturbed Thiol Profile Are Associated With Features of Metabolic Syndrome

Prospective cohort studies have revealed that plasma gamma-glutamyltransferase (GGT) activity exhibits a positive association with coronary artery disease. GGT which is equally elevated in metabolic syndrome (MS), is the major regulator of circulating concentrations of thiol compounds derived from glutathione (GSH) cleavage, ie, cysteine and cysteinyl glycine. We compared the circulating thiol profile in a cohort of patients displaying atherogenic dyslipidemia with and without MS. This cross-sectional study involved 1131 dyslipidemic patients in primary prevention of whom 26% presented with MS. GGT activity and plasma cysteinyl-glycine and cysteine concentrations were higher in MS patients; by contrast, levels of GSH were significantly lower (P<10 to 4 for all comparisons versus patients without MS). We compared patient groups on the basis of the number of MS criteria which were concomitantly present. A progressive decrease in glutathione levels in contrast to a progressive increase in both cysteinyl-glycine and cysteine levels, and GGT activity, was observed as a function of the number of MS components in the overall population (P for trend <10(-6)). Dyslipidemic patients exhibiting MS are characterized by elevated GGT activity which is associated with perturbed metabolism of thiol compounds.

Letter Regarding Article by Ruttmann et al, “γ-Glutamyltransferase as a Risk Factor for Cardiovascular Disease Mortality: An Epidemiological Investigation in a Cohort of 163 944 Austrian Adults”

To the Editor: In their article, Ruttmann et al1 showed that γ-glutamyltransferase(GGT) was independently associated with cardiovascular (CV) mortality. GGT was significantly correlated with components of the metabolic syndrome,2 including uric acid level, but waist circumference was not measured. Measurement of GGT activity is a very commonly used diagnostic test for liver dysfunction, and it increases with alcohol consumption and steatosis. Elevation of hepatic enzyme activities occurs frequently in patients with multiple CV risk factors. Indeed, we have shown that approximately one fourth of a population of 8501 dyslipidemic patients3 displayed hepatic enzymatic elevations. We found correlation coefficients similar to those reported by Ruttmann et al1 when GGT, aspartate aminotransferase, or alanine aminotransferase was selected. In subgroup analysis, the relation between waist circumference, body mass index (BMI), and GGT (n=1911) was …

Rank in Self-Defense Forces and Risk Factors for Atherosclerotic Disease

Socioeconomic status is associated with prevalence of and risk for atherosclerotic disease. We investigated the relationship between rank in the Self-Defense Forces (SDFs) and risk factors for atherosclerotic disease among middle-aged, male, SDFs personnel. Subjects were classified into five groups according to their ranks in the SDFs, i.e., class 1 (lowest, n = 289), class 2 (low, n = 170), class 3 (middle, n = 229), class 4 (high, n = 197), and class 5 (highest, n = 89). Low rank was associated with current cigarette smoking, alcohol abstaining, and poorer vegetable consumption. It was also associated with prevalence of type 2 diabetes, elevated gamma-glutamyltransferase activity, and high white blood cell counts. Prevalence of obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, or hyperuricemia was not associated with rank in this population. Rank may be regarded as one of the markers that reflect individual health states among middle-aged male personnel.

Associação da gama-glutamil transferase e a síndrome metabólica em mulheres obesas

To evaluate the correlation of gamma-glutamyl transferase (GGT) activity to the presence and number of abnormalities of the metabolic syndrome (MS). We have studied 353 women consecutively admitted into the obesity outpatient unit, aged 39.0 +/- 11.4 years and body mass index 41.3 +/- 7.3 kg/m2. All patients were asymptomatic, had no history of alcohol abuse or liver disease. National Cholesterol Education Program--Adult Treatment Panel III criteria for diagnosing MS were applied. The frequency of the MS was 50.7% in the patients. The frequency of elevated GGT activity was higher in patients with MS than without it (32% versus 20%, p = 0.05). The average GGT concentration in patients with the MS was significantly higher than in non SM patients (52.8 +/- 42.3 U/L; Md: 40.0 versus 40.1 +/- 28.8 U/L; Md: 33.0, p = 0.0001). It was also higher in patients with each one abnormality of the MS, when compared to those without it. In patients with association of three abnormalities of the MS, the mean GGT activity was 51.0 +/- 39.2 U/L (Md: 36.0); in those with four, 50.8 +/- 50.4 U/L (Md: 40.5); and five, 64.8 +/- 32.3 U/L (Md: 61.0). There were positive correlations between GGT and glucose, triglycerides or blood pressure (systolic and diastolic). GGT activity was associated to the presence and the number of abnormalities of the MS, as well as to each one abnormality of the MS in obese women.

Determinants of gamma-glutamyltransferase: positive interaction with alcohol and body mass index, negative association with coffee.

gamma-Glutamyltransferase is widely used as a marker of alcohol intake although its performance is poor. This might be related to other conditions influencing gamma-glutamyltransferase activity. The authors studied determinants of gamma-glutamyltransferase activity in a random sample (n = 6,010) drawn from the general population aged 25-64 years in Finland in 1992. In regression analysis, coffee intake and drinking boiled coffee were significantly (p < 0.01) negatively related to gamma-glutamyltransferase, whereas age, male gender, the number of cigarettes per day, serum total cholesterol and high density lipoprotein cholesterol, heart rate, and diastolic blood pressure were significantly positively related to gamma-glutamyltransferase. A significant (p = 0.02) positive interaction was observed between alcohol intake and body mass index. In logistic regression analysis, the proportion of elevated gamma-glutamyltransferase values (> or = 50 U/liter) was significantly decreased, compared with lifelong abstainers, at the alcohol intake level of < 40 g/week (odds ratio (OR) = 0.51, 95% confidence interval (CI) 0.29-0.92) and significantly increased at the level of > or = 300 g/week (OR = 2.81, 95% CI 1.35-5.85) among nonobese subjects (body mass index < 27 kg/m2). Among obese subjects, the respective proportion was significantly increased at the alcohol intake level of > or = 40 g/week (OR = 2.02, 95% CI 1.11-3.68). The proportion of elevated gamma-glutamyltransferase values was significantly decreased at the coffee intake levels of both four to six cups a day (OR = 0.44, 95% CI 0.31-0.62) and seven or more cups a day (OR = 0.36, 95% CI 0.24-0.53). In addition, drinkers of boiled coffee had elevated gamma-glutamyltransferase values more often than drinkers of filtered or instant coffee (OR = 0.59, 95% CI 0.42-0.84). No effects of alcoholic beverage preference were observed. Elevated gamma-glutamyltransferase activities appear to be related to heavy alcohol intake among the nonobese and to very light intake among obese subjects. Coffee appears to decrease gamma-glutamyltransferase activity.

Photosensitization Outbreak in Shorthorn Calves in Missouri

Photosensitization (PS) occurred in Shorthorn calves from 3 herds in Boone County, Missouri, in late August and early September 1989. In herd 1, 3 calves, 3-4 weeks old, from a herd of 35 cows with calves were mildly photosensitized. The cattle were confined to 37 acres of permanent pasture of mixed grass and red clover undersown in the previous year’s wheat crop. Skin lesions were most conspicuous on sparsely haired areas around the face and ears. According to the owner, these calves had avoided exposure to full sun for the previous 2 weeks. Two of the calves had slightly elevated gamma glutamyl transferase (GGT) activity. Other evidence of mild liver damage was indicated by a slight elevation in bilirubin (Table 1). These calves recovered during the next week. In herd 2, the 8 affected calves were 2-3 weeks old. The calves and dams were kept in a 4-acre pasture of fescue and red clover. On September 1, the owner noticed flaking skin and hair loss on the backs of the ears of several calves. More calves were affected the next day, and hair loss along the dorsal midline was evident. All calves were photophobic, and 6 of the 8 had diarrhea. At clinical examination on September 6, all 8 calves had lesions evident at various locations (8/8 ears, 6/8 head, 5/8 withers, 4/8 back, and 2/8 dewlap). Other signs of moderate PS included lacrimation, erythema, cutaneous edema, fissuring of the epithelium, and scattered crusting of serum on nonpigmented exposed skin. Serum values for aspartate aminotransferase (AST) were within the normal range. Elevated GGT activity was compatible with damage to the biliary tree. Recovery occurred during the next 3 weeks. Photosensitization is the development of hyperreactivity of the skin to sunlight. The photoreactive molecule, synonymous with photosensitizer, functions as an energy transducer to convert light energy into molecular electronic energy in the form of activated chemical species. Specific biochemical and functional effects of PS reactions include formation of photoadducts with DNA and proteins, peroxidation of lipids, photo-oxidation of membrane proteins, inhibition of transport of essential metabolites, and leakage of lysosomal enzymes. Irrespective of the cause, clinical PS resembles a severe sunburn. The progressive clinical manifestation of PS consists of lacrimation, photophobia, erythema, cutaneous edema, fissuring of the epithelium, exudation and crusting of serum, and necrosis and sloughing of nonpigmented exposed skin Corneal edema is also evident in many cases. Additional clinical signs consistent with liver damage commonly seen in secondary PS include icterus, anorexia, and depression.

Differentiation of cholestatic jaundice in infants: Utility of diethyl-IDA

Time-activity curves of technetium-labeled diethyl-IDA were used to evaluate 31 patients in an effort to differentiate infants with cholestatic jaundice. Results can be obtained rapidly with minimal radiation exposure and no known secondary effects. The combination of diethyl-IDA time-activity curves and gamma glutamyl transferase activity was found to discriminate biliary atresia from neonatal hepatitis. The group with neonatal hepatitis was characterized by abnormal, yet lower, gamma glutamyl transferase activities and diethyl-IDA time-activity curves which peaked within 1 minute of injection, yet decayed in a manner similar to cardiac activity. The group with biliary atresia was characterized by elevated gamma glutamyl transferase activities, hepatic peaks at 8 minutes and markedly delayed decay. In that early operative intervention is associated with increased survival in biliary atresia, prompt differentiation should improve prognosis.