High GGT Research Articles

Analysis of different diagnostic methods for differentiating biliary atresia from hepatitis syndrome

Objective To retrospectively evaluate different methods (laboratory tests,liver / gallbladder ultrasound and magnetic resonance cholangiopancreatography)in differentiating biliary atresia from infant hepatitis syndrome.Methods Seventy infants with cholestatic jaundice,50 cases of biliary atresia and 20 cases of infant hepatitis syndrome were studied prospectively from January 2010 to December 2012.All cases underwent abdominal ultrasound and magnetic resonance cholangiopancreatography.The accuracy,sensitivity,specificity and predictive values of these various methods were compared.Also the laboratory parameters were statistically analyzed and compared between groups.Results Patients with BA had significantly higher GGT values at presentation [(743.5 ± 564) IU/L] compared with infants with IHS [(198.8 ± 197.8) IU/L],showing statistically significant difference (P ＜ 0.05).The sensitivity,specificity,and accuracy of the ultrasound in diagnosis of BA were 84.0％ 、100.0％ 、88.6％ respectively(P ＜ 0.05).The values for magnetic resonance cholangiopancreatography were 82.0％ 、80.0％ 、81.4％ (P ＜ 0.05).Conclusion Currently,the method of ultrasound is more reliable than MRCP for differentiating biliary atresia from infant hepatitis syndrome. Key words: Biliary atresia; Infant hepatitis syndrome; Differential diagnosis

PO-0101 Progressive Familial Intrahepatic Cholestasis In Saudi Arabia

<h3>Background</h3> Progressive familial intrahepatic cholestasis (PFIC) is a rare inherited autosomal recessive disease where patients develop severe cholestasis progressing to biliary cirrhosis and chronic liver failure, usually during the first decade of life. <h3>Aim</h3> To review the clinical presentation, familial involvement and outcome of patients with PFIC in Saudi Arabia. <h3>Methods</h3> A retrospective study for patients who were diagnosed to be PFIC based on gene study between 2000–2013. <h3>Results</h3> 48 patients were confirmed by gene test to have PFIC: 5/type 1, 27/type 2, and 16/type 3. Consanguinity is seen in all patients (100%) and 31 patients (64%) having positive family history of liver diseases All PFIC type 1 patients presented with jaundice, poor growth, hepatomegaly, normal hearing and GGT. Diarrhoea in 4 patients (80%) Two patients (40%) underwent liver transplantation. Of the 27 patients with PFIC type 2, 24 patients (88%) with jaundice 22 patients (81%) and itching 3 patients (11%), hepatomegaly in 23 patients (85%), and 6 patients (22%) with signs of rickets. Biochemically three patients (11%) have high GGT on presentation and the rest of patients (88%) had normal GGT and normal cholesterol and 9 patients (33%) had coagulopathy (INR &gt;1.3). Fifteen patients (55%) underwent liver transplantation; three patients (11%) died. 16 patients with PFIC type 3 presented after 2 years of age, 6 patients (37%) with only jaundice in 5 patients (31%) and 4 patients (25%) with only itching, hepatomegaly in 14 patients (93%) and one patient (6%) with signs of rickets. Biochemically one patient (6%) had normal GGT, and two patients (12%) had coagulopathy on presentation. One patient (6%) underwent liver transplantation. <h3>Conclusion</h3> The vast majority of patients with PFIC type 1 and 2 present in the first two years and have normal GGT, while type 3 present after two years and have high GGT. However, GGT can be high in PFIC type 2 (11%) as it can be normal in PFIC type 3 (6%). One third of patients required liver transplant.

Prognostic value of serum γ-glutamyl transferase in unresectable hepatocellular carcinoma patients treated with transcatheter arterial chemoembolization combined with conformal radiotherapy.

The detection of γ-glutamyl transferase (GGT) has previously been reported to be useful in the diagnosis in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the baseline serum GGT levels in patients with intermediate HCC (Barcelona Clinic Liver Cancer stage B) following treatment with transcatheter arterial chemoembolization (TACE) combined with three-dimensional conformal radiotherapy (3DCRT). A total of 154 intermediate HCC patients with Child-Pugh grade A were retrospectively investigated. Receiver operating characteristic (ROC) analysis was used to determine the optimal threshold for the GGT serum levels, and univariate and multivariate analyses were used to establish the prognostic factors. The median overall survival (OS) time was 24.3 months. The optimal threshold for GGT was 85 U/L (sensitivity, 75.13%; specificity, 69.81%; and area under the ROC curve, 0.763). The one-, three- and five-year OS rates were 79.9, 49.7 and 17.2%, respectively, for patients with low GGT levels (≤85 U/l) and 52.3, 22.1 and 8.5%, respectively, for patients with high GGT levels (>85 U/l) (P=0.007). The results indicated that the serum GGT level was an independent prognostic factor (hazard ratio=2.32; P=0.007) for OS. Furthermore, in subgroups stratified according to serum α-fetoprotein, gross tumor volume and radiation dose, serum GGT was also found to correlate with OS (P<0.05). Therefore, the baseline GGT level may be a significant prognostic factor for intermediate HCC patients with Child-Pugh grade A following TACE combined with 3DCRT.

The variance and significance of glutamyl transpeptidase level under different statuses of glucose metabolism

The crowd were divided to 3 groups according to glucose tolerance:normal glucose tolerance,impaired glucose regulation,and new type 2 diabetes,the data was analyzed.The result showed that as the severity of abnormal glucose metabolism,the serum GGT gradually advanced,early insulin secretion index descended,The levels of resistance index,fasting and postprandial blood sugar,and glycosylated hemoglobin all raised.The serum GGT and early insulin secretion index was inversely correlated.The higher GGT level was an independent risk factors of abnormal glucose metabolism. Key words: Glutamyl transpeptidase ; Diabetes mellitus, type 2 ; Early insulin secretion index

Phase IV Prospective Clinical Study to Evaluate the Effect of Taurine on Liver Function in Postsurgical Adult Patients Requiring Parenteral Nutrition

Taurine's role in bile acid metabolism and anti-inflammatory activity could exert a protective effect on hepatobiliary complications associated with parenteral nutrition (PN). In this study, the effects of 2 amino acid solutions, with and without taurine, on liver function administered to nonacutely ill postsurgical patients as part of a short-term PN regimen were prospectively compared. Adult patients randomly received (double-blind) Tauramin 10% or a standard PN solution without taurine as the control (1.5 g amino acid/kg body weight [bw]/d; infusion rate of ≤4 mg glucose/kg bw/d) for a period of 5-30 days. γ-Glutamyl transpeptidase (GGT) and other indicators of liver function, glucose metabolism, lipid profile, inflammation markers, and treatment safety data were collected. Thirty-five patients receiving taurine PN and 39 receiving control PN were enrolled (intention-to-treat [ITT] population). Most patients (n = 62) discontinued after day 7 of follow-up (per-protocol [PP] population: n = 24 and n = 27, respectively). ITT patients with high GGT values after 5 days of PN comprised 68.6% and 64.1%, respectively. The mean change in GGT values with respect to the baseline values was 167 ± 192 and 157 ± 185 IU/L, respectively. Low-density lipoprotein (LDL) cholesterol levels after 7 days of PN were significantly decreased in the taurine PN group of PP patients (-2.83 ± 30.9 vs 23.9 ± 27.0 mg/dL for control PN; P < .05). None of the adverse events reported (taurine PN: n = 6; control PN: n = 7) were treatment related. PN solutions with and without taurine had similar effects on liver function parameters, except for an LDL reduction in PN with taurine, when administered to nonacutely ill postsurgical patients in the short term (5-7 days).

Relationship between blood mercury concentrations and serum γ-glutamyltranspeptidase level in Korean adults using data from the 2010 Korean National Health and Nutrition Examination Survey

BackgroundMercury and serum γ-glutamyltranspeptidase (GGT) play an important role in anti-oxidant mechanisms. This study aimed to investigate the association between blood mercury concentrations and GGT in Korean men and women. MethodsA nationwide cross-sectional study was conducted to examine the relationship between blood mercury concentration and serum GGT among 1959 subjects (aged 20–87y; 965 men, 994 women), using data from the 2010 Korean National Health and Nutrition Examination Survey. The odds ratios (ORs) and 95% confidence intervals (CIs) for high GGT (≥75th percentile) for both men and women were calculated across blood mercury quartiles using multiple logistic regression analyses. ResultsThe mean values of BMI, waist circumference, diastolic blood pressure, total cholesterol, and triglycerides were highest in the highest quartile of blood mercury concentrations in both sexes. GGT levels gradually increased in accordance with blood mercury quartiles. Compared to the lowest quartile of blood mercury concentrations, the adjusted OR (95% CI) for high GGT of the highest quartile was 2.59 (1.51–4.43) in men and 2.03 (1.13–3.67) in women. ConclusionWe found a positive relationship between blood mercury concentration and serum GGT level in a representative population sample of Korean adults.

An association between serum γ-glutamyltransferase and proteinuria in drinkers and non-drinkers: a Japanese nationwide cross-sectional survey

The association between alcohol consumption and chronic kidney disease (CKD), characterized by reduced glomerular filtration rate and proteinuria, is controversial. Recent studies suggest that serum γ-glutamyltransferase (GGT) level, a conventional marker of excessive alcohol consumption, predicts the CKD incidence. Little information is available on the difference in the clinical impact of alcohol consumption and GGT on proteinuria. The present cross-sectional survey included 332,296 Japanese people aged ≥40years in 2008. To examine the associations of GGT and alcohol consumption with proteinuria, 134,600 men and 197,696 women were classified into 20 categories based on GGT quartiles and alcohol consumption categories, and their prevalence rate ratios (PRR) of proteinuria defined as ≥1+ of dipstick urinary protein were calculated after adjusting for clinically relevant factors. Prevalence of proteinuria was 7.5 and 3.7% in men and women, respectively. In both gender an association between alcohol consumption and proteinuria was in a J-shaped fashion with the lowest PRR of mild drinkers with ≤19g/day of ethanol consumption, whereas an association between serum GGT level and proteinuria was linear. Compared with rare drinkers in the lowest GGT quartile, the subjects in higher GGT quartiles had a higher probability of proteinuria, irrespective of alcohol consumption. An optimal cutoff level of serum GGT was 43.6 and 23.2IU/L in men and women, respectively. The subjects with higher serum GGT level had a higher probability of proteinuria, regardless of alcohol consumption, suggesting that GGT has a clinically greater impact on CKD than alcohol consumption.

Hepatic Glucose Uptake Is Increased in Association with Elevated Serum γ-Glutamyl Transpeptidase and Triglyceride

Subjects with fatty liver disease (FLD) can show increased hepatic 2-deoxy-2-((18)F)fluoro-D-glucose (FDG) uptake, but the role of hepatic inflammation has not been explored. We investigated whether hepatic inflammatory response, as implicated by elevated serum markers, is associated with increased liver FDG uptake in FLD. Liver sonography and FDG positron emission tomography was performed in 331 asymptomatic men with nonalcoholic FLD (NAFLD), 122 with alcoholic FLD (AFLD), and 349 controls. Mean standard uptake value (SUV) of liver FDG uptake was compared to cardiac risk factors and serum markers of liver injury. Hepatic FDG mean SUV was increased in NAFLD (2.40 ± 0.25) and AFLD groups (2.44 ± 0.25) compared to controls (2.28 ± 0.26; both P < 0.001). Both FLD groups also had higher serum γ-glutamylranspeptidase (GGT), triglyceride (TG), hepatic transaminases, and LDL. High GGT and TG levels were independent determinants of increased FDG uptake for both FLD groups. Hepatic mean SUV significantly increased with high compared to low GGT for NAFLD (2.48 ± 0.28 vs. 2.37 ± 0.24), AFLD (2.51 ± 0.27 vs. 2.39 ± 0.23), and control groups (2.39 ± 0.22 vs. 2.26 ± 0.26). High TG increased hepatic mean SUV in AFLD and control groups. Furthermore, serum GGT and TG levels significantly correlated to hepatic mean SUV in all three groups. Hepatic FDG uptake is closely associated with elevated TG and GGT regardless of the presence of FLD. Thus, inflammation response may play a major role in increased hepatic glucose uptake.

Elevation of serum γ-glutamyltransferase as a predictor of aggressive tumor behaviors and unfavorable prognosis in patients with intrahepatic cholangiocarcinoma

γ-Glutamyltransferase (GGT) has been used as a diagnostic biomarker for hepatobiliary disease. However, little is known about its role in intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to validate the clinical significance of GGT in predicting the prognosis of ICC patients. A total of 411 patients with pathologically confirmed ICC were retrospectively analyzed. Of them, 307 patients underwent hepatectomy, 64 patients with unresectable tumors were treated with chemotherapy (n=42) or transcatheter arterial chemoembolization (n=22), and 40 patients with end-stage disease received supportive treatment. The association between GGT and the clinicopathological features and prognosis was assessed. Serum GGT levels were significantly associated with hepatitis B infection (P=0.02), the Child-Pugh grade (P=0.02), vascular invasion (P<0.001), lymph node involvement (P=0.04), and incomplete tumor encapsulation (P=0.009). Survival analysis showed that GGT was an independent predictor of a poor prognosis (hazard ratio=2.36, 95% confidence interval: 1.67-3.34, P=0.001). This prognostic value of GGT was further validated in the mass-forming, normal bilirubin, and Child-Pugh A subgroups. Subsequent recurrence analysis showed that a recurrence-free survival in patients with high GGT levels was significantly shorter than that in those with low GGT levels (6 vs. 12 months, P<0.001). The serum GGT level was an independent predictor of tumor recurrence in ICC patients (hazard ratio=1.59, 95% confidence interval: 1.07-2.37, P=0.02). Elevation of serum GGT levels is an indicator of aggressive tumor behaviors and a predictor of poor clinical outcomes. It may prove to be a useful biomarker for identifying ICC patients at high risk of early recurrence and unfavorable prognosis.

Staging, prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma after curative resection

Prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma (ICC) after curative resection were not clear. We aim to analyse prognostic factors after curative resection and evaluate adjuvant therapy and survival based on the new staging system. A retrospective analysis of 283 patients who underwent surgical exploration for ICC was performed. Staging was performed according to the 7th edition AJCC staging manual. Univariate and multivariate analyses were used to evaluate independent prognostic factors. The difference for OS at different TNM stages after R0 resection was significant (P<0.001). Despite regional lymph node metastasis, tumour number and vascular invasion, serum GGT level was also an independent prognostic factor for OS of patients after R0 resection. The incidence of biliary and vascular invasion was significantly higher in high GGT group than in normal GGT group. Factors predictive of recurrence were multiple tumours and regional lymph node metastasis. After R0 resection, adjuvant TACE not only did not improve the OS of patients at TNM stage I (P=0.508), but significantly promoted recurrence of these patients (P=0.006). Only patients at TNM stage II, III and IV benefited from adjuvant TACE for longer survival, while the recurrence rates were not affected. The new staging system can predict the survival of ICC patients after R0 resection. High GGT level may be suggestive of biliary and vascular invasion and was an independent risk factor for OS after R0 resection. Adjuvant TACE may be indicated only for patients at advanced stages for better survival.

Association between aldehyde dehydrogenase 2 polymorphisms and the incidence of diabetic retinopathy among Japanese subjects with type 2 diabetes mellitus

BackgroundMitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies reactive aldehydes in the micro- and macrovasculature. These substrates, including methylglyoxal and 4-hydroxynonenal formed from glucose and lipids, cause protein carbonylation and mitochondrial dysfunction, forming advanced glycation end products (AGEs). The present study aimed to confirm the association between the inactive ALDH2*2 allele and diabetic retinopathy (DR).MethodsA retrospective longitudinal analysis was conducted, among 234 Japanese patients with type 2 diabetes mellitus (DM) (156 males and 78 females) who had no DR signs at baseline and were treated for more than half a year. The ALDH2*1/*2 alleles were determined using a real-time TaqMan allelic discrimination assay. Multivariate-adjusted hazard ratios (HRs) and 95% confidential intervals (CIs) for the cumulative incidence of the development of DR were examined using a Cox proportional hazard model, taking drinking habits and the serum γ-glutamyltransferase (GGT) level into consideration.ResultsThe frequency of the ALDH2*2 allele was 22.3%. Fifty-two subjects cumulatively developed DR during the follow-up period of 5.5 ± 2.5 years. The ALDH2*2 allele carriers had a significantly higher incidence of DR than the non-carriers (HR: 1.92; P = 0.02). The incidence of DR was significantly higher in the drinkers with the ALDH2*2 allele than in those with the ALDH2*1/*1 genotype (HR: 2.61; P = 0.03), while the incidence of DR in the non-drinkers did not differ significantly between the ALDH2 genotype groups (P > 0.05). The incidence of DR was significantly higher in the ALDH2*2 allele carriers with a high GGT level than in the non-carriers with a high or low GGT level (HR: 2.45; P = 0.03; and HR: 2.63; P = 0.03, respectively).ConclusionsTo the best of our knowledge, this is the first report of a significant association between the ALDH2*2 allele and the incidence of DR. These findings provide additional evidence that ALDH2 protects both microvasculature and macrovasculature against reactive aldehydes generated under conditions of sustained oxidative stress, although further investigations in larger cohorts are needed to verify the results.

Effect of Haemodynamic Changes on Epithelium-related Intestinal Injury in Off-pump Coronary Surgery

Intestinal injury is thought to play a central role in the occurrence of multiorgan dysfunction after on-pump coronary surgery. Clinical benefits of off-pump revascularisation remain, however, controversial. Hepatic enzymes and plasmatic IL-6, IL-8 and intestinal-type fatty acid binding protein (I-FABP) were determined in 20 patients (age 65-75) undergoing either on-pump (n = 10) or off-pump (n = 10) coronary surgery. Haemodynamic and biochemical parameters, catecholamine and volume therapy were monitored. Central venous pressure (CVP) was significantly higher in the off-pump group during and 12h after operation (9.5 ± 1.35 vs. 6.21 ± 0.63 mmH2O, p = 0.012). Higher GGT and GLDH levels occurred in the off-pump group and correlated with the elevated I-FABP levels at 24h (935.8 ± 83.7 vs. 370.4 ± 67.7 pg/mL, p<0.001). CVP correlated with I-FABP peak values (Pearson's coefficient 0.852). IL-6 and IL-8 were released to a lower extent in the off-pump group compared to on pump (p<0.05) at 24h (139.3 ± 27.7 vs. 279.4 ± 56.2 and 15.3 ± 7.4 vs. 38.5 ± 13.8 pg/mL) and at 72 h post-operatively (4.5 ± 2.1 vs. 30.1 ± 12.1 and 7.8 ± 1.2 vs. 17.1 ± 5.2 pg/mL). While inflammatory activation is reduced with CPB avoidance, elevated CVP during off-pump surgery is followed by temporary postoperative enterocyte damage that may threaten the normal function of the gastrointestinal system and lead - in certain groups of high risk patients--to irrecoverable injury.

Association of gamma-glutamyltransferase with severity of disease at diagnosis and prognosis of ovarian cancer

Background:Gamma-glutamyltransferase (GGT) – a membrane-bound enzyme crucially involved in the cell's detoxification pathway and apoptotic balance – is involved in tumour development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosis in gynaecologic cancers. The present study investigated the prognostic role of GGT in ovarian cancer patients.Methods:In this multicenter study, pre-therapeutic GGT levels were ascertained in 634 consecutive patients with epithelial ovarian cancer (EOC, n=567) and borderline tumour of the ovary (BTO, n=67). Gamma-glutamyltransferase serum levels were associated with clinicopathological parameters and uni- and multivariate survival analyses were performed. Immunohistochemistry of GGT was performed in ovarian cancer tissue and correlated with GGT serum levels.Results:Pre-therapeutic GGT serum levels were higher in patients with EOC (28.56 (38.24) U l−1) than in patients with BTO (20.01 (12.78) U l−1, P=0.01). High GGT serum levels were associated with advanced FIGO stage (P<0.001) and with worse overall survival in univariate (P<0.001) and multivariable analysis (P=0.02, HR 1.2 (1.1–1.5)). We further investigated the association between systemic GGT serum levels and local GGT expression in EOC tumour tissue and observed an association between these two parameters (P=0.03).Conclusion:High pre-therapeutic GGT serum levels are associated with advanced tumour stage and serve as an independent prognostic marker for worse overall survival in patients with EOC. Gamma-glutamyltransferase expression in ovarian cancer tissue is reflected in GGT serum levels.

The relationship between γ-glutamyl transferase levels and the clinical outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Serum γ-glutamyl transferase (GGT) activity has been shown to be related to the development of atherosclerosis and cardiovascular events. The aim of this study was to evaluate the prognostic value of GGT in patients with ST-segment elevation myocardial infarction (STEMI) undergoing a primary percutaneous coronary intervention (PCI). A total of 683 consecutive patients with STEMI who underwent primary PCI were evaluated. The study population was divided into tertiles on the basis of admission GGT values. A high GGT (n=221) was defined as a value in the upper third tertile (GGT>37) and a low GGT (n=462) was defined as any value in the lower two tertiles (GGT≤37). The mean follow-up time was 29 months. The in-hospital mortality rate was significantly higher in patients in the high GGT group (7.2 vs. 1.7%, P<0.001), as was the rate of adverse outcomes in patients with high GGT levels. In multivariate analyses, a significant association was found between high GGT levels and adjusted risk of in-hospital cardiovascular mortality (odds ratio=8.6, 95% confidence interval: 2.3-32.4, P=0.001). In a receiver operating characteristic curve analysis, a GGT value greater than 37 was identified as an effective cutoff point in STEMI for in-hospital cardiovascular mortality (area under curve=0.71, 95% confidence interval: 0.59-0.82, P<0.001). There were no differences in the long-term adverse outcome rates between the two groups. GGT is a readily available clinical laboratory value associated with in-hospital adverse outcomes in patients with STEMI who undergo primary PCI. However, there was no association with long-term mortality.

The role of gamma-glutamyltransferase in malignant transformation and prognosis of ovarian cancer.

e16524 Background: Gamma-glutamyltransferase (GGT) – a membrane bound enzyme crucially involved in the cell’s detoxification pathway and apoptotic balance – is involved in tumor development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosis in gynecologic cancers. The present study investigated the prognostic role of GGT in ovarian cancer patients. Methods: In this multi-center study, pre-therapeutic GGT levels were ascertained in 634 consecutive patients with epithelial ovarian cancer (EOC, n = 567) and borderline tumor of the ovary (BTO, n = 67). GGT serum levels were associated with clinico-pathological parameters and uni- and multivariate survival analyses were performed.Immunohistochemistry of GGT was performed in ovarian cancer tissue and correlated with GGT serum levels. Results: Pre-therapeutic GGT serum levels were higher in patients with EOC (28.56 [38.24] U/L) than in patients with BTO (20.01 [12.78] U/L, p = 0.01). High GGT serum levels were associated with advanced FIGO stage (p&lt;0.001) and with worse overall survival in univariate (p &lt; 0.001) and multivariable analysis (p=0.02, HR 1.2 [1.1-1.5]). We further investigated the association between systemic GGT serum levels and local GGT expression in EOC tumor tissue and observed an association between these two parameters (p = 0.03). Conclusions: High pre-therapeutic GGT serum levels are associated with advanced tumor stage and serve as an independent prognostic marker for worse overall survival in patients with EOC. GGT expression in ovarian cancer tissue is reflected in GGT serum levels.

Association between serum γ-glutamyltransferase levels and coronary microvascular function

Serum γ-glutamyltransferase (GGT) level is an independent risk factor for cardiovascular (CV) disease, and there is a strong association between serum GGT levels and most CV risk factors. However, the role of the serum GGT level as an independent risk factor for coronary microvascular function remains controversial. We aimed to determine whether the serum GGT level is independently and specifically associated with coronary flow reserve (CFR) impairment in normal individuals. We examined healthy individuals who did not have any major CV risk factors (277), of whom CFR was achieved in 263 (95%). They were divided into three groups according to serum GGT levels. In each participant, CFR was measured using an Acuson Sequoia C256 Echocardiography System. Participants with high GGT levels had significantly impaired CFR compared with those with intermediate and low GGT levels (2.82±0.49 vs. 2.71±0.51 and 2.44±0.48 U/l; P<0.0001). After adjusting for potential confounders, including sex, BMI, blood pressure, lipids, and glucose, we found that the serum GGT and high-sensitivity C-reactive protein levels were associated independently with CFR impairment (b=-0.205, P=0.007; b=-0.172, P=0.024). We also found that the serum GGT level was a good predictor of low CFR at the receiver-operating characteristic curve. The area under the curve was 75% [95% confidence interval, 0.65-0.86], and the serum GGT level was significantly predictive of a low CFR (P<0.0001). These results support a role for the serum GGT level as an independent marker of coronary microvascular damage and inflammation in normal individuals without concomitant risk factors.

Serum gamma-glutamyltransferase and the burden of atherosclerosis in patients with acute coronary syndrome

We evaluated the relationship between serum gamma-glutamyltransferase (GGT) levels and the burden of atherosclerosis in patients with acute coronary syndrome (ACS). This study involved 180 patients (139 male, 41 female; mean age 63±11 years) with the diagnosis of ACS (non-ST elevation myocardial infarction and unstable angina) who underwent coronary angiography on the first day after hospital admission. The burden of atherosclerosis was assessed by the number of involved vessels, and the Gensini and Syntax scores. Serum GGT levels were measured by enzymatic caloric test. Patients with high Syntax scores (>=33) were more frequently diabetic, hypertensive, and had higher GGT and creatinine levels compared to the patients with low Syntax scores (<=23). Similarly, patients with >=3 diseased vessels were more frequently diabetic, hypertensive, and smokers. In addition, these patients were older and had higher serum glucose, urea and GGT levels. Correlation analysis revealed that the level of GGT was significantly associated with Gensini and Syntax scores, number of diseased vessels, and the number of critical lesions (r=0.378 p<0.001, r=0.301 p<0.001, r=0.159 p=0.036, r=0.355 p<0.001, respectively). Multivariate linear regression analysis demonstrated that increased GGT level was an independent risk factor for high Gensini and Syntax scores (p=0.029 and p=0.035, respectively), together with age (p=0.001 and p=0.002, respectively) and serum glucose levels (p=0.017 and p=0.012, respectively). Serum GGT levels on admission are associated with increased burden of atherosclerosis in patients with ACS. This may account for the cardiovascular outcomes associated with increased GGT levels.

Kava ichthyosis: a nitric oxide synthase inhibition?

Purpose: Kava is a traditional Pacific beverage made from the root of Piper methysticum . It is mainly used for its sedative properties due to lipophilic lactones called kavalactones. Various preparations or medications made from this plant can be purchased via the internet. Kava action mechanisms include cell membrane stabilisation, inhibition of intracellular Ca 2+ increase and enzyme inactivation. Chronic or heavy kava consumption results in the skin taking on a scaly aspect. Biologically, an isolated increase in serum gamma-glutamyltransferase is apparent. Cases of sudden death after heavy kava sessions have occurred in Australia, and nine cases in New Caledonia were reported by our forensic laboratory during the 2000−mid-2013 period. No clear explanation has been given. We describe the possible action mechanism. Methods: We monitored 116 heavy kava drinkers. A multiple-probe drug cocktail was used on six other volunteers, all heavy and chronic kava drinkers, before and after kava abstinence to carry out CYP450 phenotyping. Results: The heavy chronic drinkers showed an isolated increase in GGT without any biological or clinical abnormality other than scaly skin. With the multiple-probe drug cocktail an inhibition of the CYP1A2 isoenzyme was demonstrated. In kava dermopathy a lack of epithelial nitric oxide production leading to an increased S-nitroso-glutathione degradation by the epithelial gamma-glutamyltransferase should be considered. Conclusions: As there are close structural and functional similarities between nitric oxide synthase (NOS) and CYP1A2, and as we have formerly demonstrated that kava inhibits CYP1A2, an inhibition of NOS in chronic kava drinkers must be studied to see if ichthyosis can be explained, and if high blood GGT level is a reflection of epithelial cell GGT activity. Furthermore, a decrease in NO bioavailability can cause myocardial and vascular dysfunctions and hypercoagulability, leading to acute coronary syndrome or ischemic stroke. This mechanism should be explored in cases of “post-kava session sudden death”.

Coffee consumption, serum γ-glutamyltransferase, and glucose tolerance status in middle-aged Japanese men

Recently, coffee consumption has been related to decreased risk of type 2 diabetes mellitus (DM) among those with high levels of serum γ-glutamyltransferase (GGT). We examined the association between coffee and glucose tolerance, determined by a 75 g oral glucose tolerance test, and the effect modification of serum GGT on the association. The study subjects were 5320 men aged 46-60 years who received a health examination at two Self-Defense Forces hospitals from January 1997 to March 2004. Those medicated for DM were excluded. Coffee consumption was classified into <1, 1-2, 3-4, and ≥5 cups/day. Statistical adjustment was made for age, body mass index, smoking, alcohol use, leisure-time physical activity, green tea consumption, parental diabetes, hospital, and rank in the Self-Defense Forces. Men with normal glucose tolerance, isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG/IGT, and type 2 DM numbered 3384, 398, 790, 348, and 400, respectively. The prevalence odds of isolated IGT, combined IFG/IGT, and type 2 DM, but not of isolated IFG, decreased with increasing consumption of coffee. An inverse association with coffee was observed for isolated IGT in both low (≤40 IU/L) and high (>40 IU/L) GGT groups, and for combined IFG/IGT and type 2 DM in the latter group. Coffee drinking is protective against glucose intolerance. A possible effect modification of GGT on the coffee-DM association warrants further studies.

Prognostic value of biochemical liver parameters in neonatal sepsis‐associated cholestasis

The aim of the study was to evaluate the significance of total bilirubin, aspartate transaminase (AST), alanine transaminase and gamma-glutamyltransferase (GGT) for predicting outcome in sepsis-associated cholestasis. A retrospective cohort review of the hospital records was performed in 181 neonates admitted to the Neonatal Care Unit. A comparison was performed between subjects with low and high liver values based on cut-off values from ROC analysis. We defined poor prognosis to be when a subject had prolonged cholestasis of more than 3.5 months, developed severe sepsis, septic shock or had a fatal outcome. The majority of the subjects were male (56%), preterm (56%) and had early onset sepsis (73%). The poor prognosis group had lower initial values of GGT compared with the good prognosis group (P = 0.003). Serum GGT (cut-off value of 85.5 U/L) and AST (cut-off value of 51 U/L) showed significant correlation with the outcome following multivariate analysis. The odds ratio (OR) of low GGT and high AST were OR 4.3 (95% CI:1.6 to 11.8) and OR 2.9 (95% CI:1.1 to 8), respectively, for poor prognosis. In subjects with normal AST values, those with low GGT value had relative risk of 2.52 (95% CI:1.4 to 3.5) for poorer prognosis compared with those with normal or high GGT. Serum GGT and AST values can be used to predict the prognosis of patients with sepsis-associated cholestasis.