Elevated Gamma-glutamyl Transferase Levels Research Articles

Hepatoprotective and Antioxidant Activities of Polyphenolic Extract of Pyrus communis Leaf in Carbon tetrachloride–Treated Albino Wistar Rats

Polyphenols are active plant compounds that are reportedly capable of eliminating or limiting the deleterious side effects of free radicals and consequently restoring the functional integrity of important organs such as the liver. This study investigated the liver-protecting and antioxidant activities of PEP.c (Polyphenol leaf extract of Pyrus communis) against carbon tetrachloride-induced hepatotoxicity in Wistar rats. Liver damage was induced via intraperitoneal (i.p.) injection of 1.5 mL/kg body weight (b.w.) of 50% carbon tetrachloride (CCl4) in olive oil on the 7th day of extract/drug administration. In-duction of CCl4 significantly (P < 0.05) increased the activities of serum gam-ma-glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) as well as a significant decrease (P < 0.05) in the serum level of total protein and the activity of superoxide dismutase and glutathione in the liver tissue with a concomitant increase in malondialdehyde (MDA) level. Oral administration of PEP.c (50, 100, and 250 mg/kg b.w.) for 7 days, significantly (P < 0.05) reduced the elevated serum levels of serum GGT, AST, ALT, ALP and increased the level of total protein as compared to CCl4-induced hepatotoxic-untreated group. However, administration of PEP.c significantly (P < 0.05) decreased concentration of malondialdehyde and increased the activity of the superoxide dismutase (SOD) as well as enhanced glutathione (GSH) level in the liver tissue. Results were compared to N-acetylcysteine, a known liver-protecting agent. Results from histopathological evaluation also supported the hepatoprotective-city of PEP.c in the CCl4-induced albino Wistar rats. The results of this study suggested that PEP.c can be used as a safe and alternative drug for the prevention and management of liver injury.

Serum Gamma-Glutamyl Transferase and C-Reactive Protein in Essential Hypertension

ABSTRACT Background: Hypertension is known to be one of the major causes of the global burden of many diseases. It is proving to be a critical medical and public health issue. Previous studies have drawn inconsistent conclusions about the risk of hypertension and its association with gamma-glutamyl transferase and C-reactive protein (CRP). CRP is a marker of systemic inflammation and has been postulated to increase the risk of hypertension. Gamma-glutamyl transferase catalyzes the transfer of gamma-glutamyl functional groups from molecules such as glutathione to an acceptor that may be an amino acid, a peptide, or water. This study was undertaken to evaluate gamma-glutamyl transferase and CRP in essential hypertension and determine the association of these parameters with hypertension, if any. Materials and Methods: A total of 104 subjects (52 hypertensive cases and 52 healthy controls) between the ages of 30 and 50 were recruited after imposing certain inclusion and exclusion criteria. Gamma-glutamyl transferase and CRP were estimated using commercially available kits. All the data were tested at a 5% level of significance. Results: Mean levels of gamma-glutamyl transferase and CRP were found to be significantly increased in patients with essential hypertension compared to controls. Elevated levels of gamma-glutamyl transferase and CRP are associated with oxidative stress and inflammation, which are in turn considered to be major factors involved in the pathogenesis of hypertension. Conclusion: In conclusion, our study suggests that gamma-glutamyl transferase and C-reactive protein are independently associated with hypertension.

Hepatic and Renal Functions in HIV-Positive Children with Malaria in Western Kenya

Background: The burden of HIV and malaria co-infection lies disproportionately in the Sub-Saharan Africa region which bears most of the malaria endemic zones. While both malaria and HIV are known to dysregulate hepatic and renal functions, the combined effect of co-infection with malaria and HIV on hepatic and renal function among children remains poorly characterized. Objective: To assess liver and renal functions in HIV-malaria co-infected children in Western Kenya. Methods: A cross-sectional study was conducted among children aged 6-59 months with HIV and malaria coinfection at Kakamega County Referral Hospital, Western Kenya. A total of 138 children were enrolled. Microscopy and clinical chemistry analysers were used to diagnose malaria, and assay hepatic and renal function parameters respectively. Results: HIV positive-malaria positive cases had significantly higher serum creatinine and urea levels compared to the HIV positive-malaria negative controls. Likewise, serum levels of the alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), total protein, albumin and globulin were significantly elevated in the HIV and malaria-positive cases compared to HIV-positive and malaria-negative controls. Significantly higher proportions of children with HIV and malaria coinfection also had elevated serum levels of ALT, ASP, GGT, total proteins, albumin and globulin compared to children without coinfection. Serum levels of Alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH) were comparable in both groups. Conclusion: Co-infection with HIV and malaria among children is generally associated with disrupted hepatic and renal function parameters.

Independent and additive effects of binge drinking and obesity on liver enzymes: a cross-sectional analysis using the Korean National Health Insurance Service data.

Binge drinking (BD) has been associated with elevated liver enzymes, but the joint association of BD and adiposity with liver enzymes is understudied. We aimed to examine the combined association of BD and obesity with elevated liver enzymes. Data were obtained from 285,600 patients in the Korean National Health check-up program during 2009-2015. Level I BD (BDI) was defined as alcohol consumption of >60 g (men) or >40 g (women) on one occasion in the previous year. High-intensity BD (HIBD) corresponded to at least two times the BDI levels. General and abdominal obesity were defined by body mass index and waist circumference. Logistic regression was used to examine the independent and joint associations of BD and obesity with elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels. Relative excess risk (RERI), attributable proportion (AP), and synergy index (SI) were calculated to estimate the additive interaction effects. The mean age was 42.1 ± 0.03 years and 50.2% were women. Elevated ALT [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.02-1.16], AST (OR 1.16, 95% CI 1.11-1.23), and GGT (OR 1.84, 95% CI 1.05-1.94) were associated with HIBD. Higher odds of elevated ALT (OR 3.57, 95% CI 3.43-3.71), AST (OR 3.47, 95% CI 3.37-3.58), and GGT (OR 2.10, 95% CI 1.98-2.12) were observed in individuals with general obesity. A similar trend was observed for abdominal obesity. The RERI, AP, and SI for the interaction effect of BD and general obesity were 23%, 7%, and 13% for elevated AST levels, and 67%, 24%, and 58% for elevated GGT levels, respectively. Similar effects were observed for the interaction between BD and abdominal obesity. Obesity aggravated the odds of elevated liver AST and GGT levels in HIBD.

Gamma-glutamyl transferase and calculus of kidney incidence: a Mendelian randomization study

Elevated Gamma-glutamyl transferase (GGT) levels are often suggestive of cholelithiasis, and previous studies have indicated that GGT is highly expressed in the urinary system. Therefore, we hypothesized that there may be an association between GGT levels and calculus of kidney (CK) incidence. To investigate this potential causal relationship, we employed Mendelian randomization (MR) analysis. Additionally, we analyzed the levels of other liver enzymes, including alanine transaminase (ALT) and alkaline phosphatase (ALP). The relationship between GGT levels and CK incidence was analyzed using two-sample Mendelian randomization. Summary Genome-Wide Association Studies data were utilized for this analysis. 33 single nucleotide polymorphisms known to be associated with GGT levels were employed as instrumental variables. We employed several MR methods including IVW (inverse variance weighting), MR-Egger, weighted median, weighted mode, and MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier). Furthermore, we conducted tests for horizontal multivariate validity, heterogeneity, and performed leave-one-out analysis to ensure the stability of the results. Overall, several MR methods yielded statistically significant results with a p-value < 0.05. The results from the IVW analysis yielded an odds ratio (OR) of 1.0062 with a 95% confidence interval (CI) of 1.0016–1.0109 (p = 0.0077). Additional MR methods provided supplementary results: MR-Egger (OR 1.0167, 95% CI 1.0070–1.0266, p = 0.0040); weighted median (OR 1.0058, 95% CI 1.0002–1.0115, p = 0.0423); and weighted mode (OR 1.0083, 95% CI 1.0020–1.0146, p- = 0.0188). Sensitivity analyses did not reveal heterogeneity or outliers. Although potential horizontal pleiotropy emerged, we speculate that this could be attributed to inadequate test efficacy. However, subsequent use of MR-PRESSO did not provide evidence of pleiotropy. Our analysis suggests a positive association between elevated GGT levels and CK incidence, indicating an increased risk of CK development. However, no causal relationship was observed between levels of ALP or ALT and CK incidence.

Association between polycyclic aromatic hydrocarbon exposure and liver function: The mediating roles of inflammation and oxidative stress

Polycyclic aromatic hydrocarbon (PAH) exposure has been associated with adverse health effects, and accumulating evidence suggests that PAH exposure may impair liver function. However, the underlying mechanisms linking PAH exposure and liver function impairment remain unclear. This study aimed to explore the association between PAH exposure and liver function biomarkers, and the mediating effects of inflammation and oxidative stress. The cross-sectional study included 155 adults and their urinary PAH metabolites (OH-PAHs) were determined, and eight liver function biomarkers were measured in paired serum samples. A comprehensive statistical analysis investigated the linear, non-linear, individual, and joint effects of the association between urinary OH-PAHs and liver function biomarkers. The results indicated significant positive associations between urinary OH-PAH concentrations and liver function biomarker levels, suggesting that PAH exposure may adversely affect liver function. 2-hydroxyfluorene was identified as the individual metabolite contributing significantly to elevated gamma-glutamyl transferase levels. Further stratification by gender revealed that this association is more pronounced in males. Moreover, we observed significant mediation effects of the oxidative stress biomarker 8-hydroxy-2′-deoxyguanosine and the inflammatory biomarkers C-reactive protein and white blood cell count on this association. The physiological responses triggered by PAH exposure are mediated by inflammation, which serves as a link between oxidative stress, cellular injury, and elevated liver enzyme levels. The results demonstrated that increased inflammation and oxidative stress mediated the association between increased urinary OH-PAHs and elevated liver function biomarkers. The results contribute to a better understanding of the potential mechanisms underlying PAH exposure's hepatotoxic effects.

Potential Causal Association between Elevated Gamma-Glutamyl Transferase Level and Stroke: A Two-Sample Mendelian Randomization Study.

Researchers have suggested a potential relationship between gamma-glutamyl transferase (GGT) level and stroke. We investigated a potential causal relationship between GGT level as exposures and stroke and stroke subtypes (cardioembolic, small vessel, and large artery) in a European population. We performed a two-sample Mendelian randomization (MR) study using the genome-wide association study (GWAS) data from the UK Biobank as the exposure set. For the outcome set, we used stroke in the GWAS data from the GIGASTROKE Consortium. We considered alcohol consumption, atrial fibrillation, and body mass index as confounders. We used PhenoScanner searches for removal of SNPs and multivariable MR analysis for assessing confounders. We observed significant causal associations between GGT level and stroke (odds ratio [OR] = 1.23, 95% CI = [1.05-1.44], and p = 0.012 with IVW; OR = 1.19, 95% CI= [1.02-1.39], and p = 0.031 with MR-PRESSO). These results were consistent after removing SNPs related to confounding factors. Similarly, in multivariable MR, GGT was associated with stroke after adjusting for confounding factors (OR = 1.30, 95% CI 1.07-1.60), p = 0.010). Because GGT level has a causal relationship with stroke, researchers should test its significance as a potential risk factor for stroke. Additional research is required to validate these results.

Increased risk of ischemic stroke associated with elevated gamma-glutamyl transferase level in adult cancer survivors: a population-based cohort study

Adult cancer survivors may have an increased risk of developing ischemic stroke, potentially influenced by cancer treatment-related factors and shared risk factors with stroke. However, the association between gamma-glutamyl transferase (GGT) levels and the risk of ischemic stroke in this population remains understudied. Therefore, our study aimed to examine the relationship between GGT levels and the risk of ischemic stroke using a population-based cohort of adult cancer survivors. A population-based cohort of adult cancer survivors was derived from the National Health Insurance Service-Health Screening Cohort between 2003 and 2005 who survived after diagnosis of primary cancer and participated in the biennial national health screening program between 2009 and 2010. Cox proportional hazards model adjusted for sociodemographic factors, health status and behavior, and clinical characteristics was used to investigate the association between GGT level and ischemic stroke in adult cancer survivors. Among 3095 adult cancer survivors, 80 (2.58%) incident cases of ischemic stroke occurred over a mean follow-up of 8.2 years. Compared to the lowest GGT quartile, the hazard ratios (HRs) for ischemic stroke were 1.56 (95% CI 0.75–3.26), 2.36 (95% CI 1.12–4.99), and 2.40 (95% CI 1.05–5.46) for the second, third, and fourth sex-specific quartiles, respectively (Ptrend = 0.013). No significant effect modification was observed by sex, insurance premium, and alcohol consumption. High GGT level is associated with an increased risk of ischemic stroke in adult cancer survivors independent of sex, insurance premium, and alcohol consumption.

GAMMA GLUTAMYL TRANSFERASE LEVELS IN PATIENTS WITH ACUTE STROKE: AN ANALYTICAL STUDY

Objectives: Stroke is a significant global health issue with a major socioeconomic burden, ranking as the second leading cause of death worldwide. While stroke rates have declined in high-income countries, they have increased in low- to middle-income countries, including India. The World Health Organization defines stroke as a disturbance of cerebral function caused by vascular factors, classified as ischemic or hemorrhagic. Methods: Ischemic stroke is primarily caused by atherosclerosis in the brain’s arteries, including the proximal aorta, leading to embolus formation. Other factors contributing to stroke include arterial stenosis, coexisting thrombosis, artery-to-artery embolism, micro atheroma, lipohyalinosis, and occlusive diseases of small brain arteries. Cardiogenic embolism, often associated with atrial fibrillation, contributes to a significant proportion of ischemic strokes. Gamma-glutamyl transferase (GGT), commonly used as a marker for alcohol consumption and liver diseases, is also linked to oxidative stress, inflammation, and atherosclerosis. Elevated GGT levels are associated with various stroke risk factors. Results: GGT plays a crucial role in cellular intake of glutathione, an important antioxidant. Paradoxically, it can generate reactive oxygen species in the presence of certain metals. Studies have found a correlation between high serum GGT levels and stroke risk, potentially due to oxidative stress and atherosclerosis progression. Conclusion: Despite its primary use as an alcohol consumption marker, GGT has emerged as a potential independent biomarker for vascular diseases, including stroke. However, limited research exists on the association between GGT and acute stroke. This study aims to evaluate GGT levels in patients with acute stroke, exploring potential differences among stroke types to better understand the impact of GGT on acute stroke.

Gamma-Glutamyltransferase Is a Predictor for Future Changes of Diabetogenic Factors in Aged Chinese-A Four-Year Follow-Up Study.

Glucose homeostasis in the body is determined by four diabetes factors (DFs): insulin resistance (IR), glucose effectiveness (GE), and the two phases of insulin secretion-first phase (FPIS) and second phase (SPIS). Previous research points to a correlation between elevated levels of gamma-glutamyl transferase (γGT) and an increased risk of type 2 diabetes. This study investigates the relationship between γGT and the four DFs in older Chinese individuals. This study involved 2644 men and 2598 women, all of whom were relatively healthy Chinese individuals aged 60 years or more. The DFs were calculated using formulas developed by our research, based on demographic data and factors related to metabolic syndrome. Pearson's correlation was utilized to assess the relationship between γGT and the four DFs. The findings suggested a positive correlation between γGT and IR, FPIS, and SPIS, but a negative correlation with GE in men. Among women, only SPIS and GE were significantly correlated with γGT. The factors showed varying degrees of correlation, listed in descending order as follows: GE, SPIS, FPIS, and IR. This study confirms a significant correlation between γGT and DFs in this population, highlighting the noteworthy role of GE.

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 &lt; 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.

An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography

We conducted an individual patient data meta-analysis to establish stiffness cut-off values for magnetic resonance elastography (MRE) in staging liver fibrosis and to assess potential confounding factors. A systematic review of the literature identified studies reporting MRE data in patients with NAFLD. Data were obtained from the corresponding authors. The pooled diagnostic cut-off value for the various fibrosis stages was determined in a two-stage meta-analysis. Multilevel modelling methods were used to analyse potential confounding factors influencing the diagnostic accuracy of MRE in staging liver fibrosis. Eight independent cohorts comprising 798 patients were included in the meta-analysis. The area under the receiver operating characteristic curve (AUROC) for MRE in detecting significant fibrosis was 0.92 (sensitivity, 79%; specificity, 89%). For advanced fibrosis, the AUROC was 0.92 (sensitivity, 87%; specificity, 88%). For cirrhosis, the AUROC was 0.94 (sensitivity, 88%, specificity, 89%). Cut-offs were defined to explore concordance between MRE and histopathology: ≥F2, 3.14kPa (pretest probability, 39.4%); ≥F3, 3.53kPa (pretest probability, 24.1%); and F4, 4.45kPa (pretest probability, 8.7%). In generalized linear mixed model analysis, histological steatohepatitis with higher inflammatory activity (odds ratio 2.448, 95% CI 1.180-5.079, p<0.05) and high gamma-glutamyl transferase (GGT) concentration (>120U/L) (odds ratio 3.388, 95% CI 1.577-7.278, p <0.01] were significantly associated with elevated liver stiffness, and thus affecting accuracy in staging early fibrosis (F0-F1). Steatosis, as measured by magnetic resonance imaging proton density fat fraction, and body mass index(BMI) were not confounders. MRE has excellent diagnostic performance for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Elevated inflammatory activity and GGT level may lead to overestimation of early liver fibrosis, but anthropometric measures such as BMI or the degree of steatosis do not. This individual patient data meta-analysis of eight international cohorts, including 798 patients, demonstrated that MRE achieves excellent diagnostic accuracy for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Cut-off values (significant fibrosis, 3.14kPa; advanced fibrosis, 3.53kPa; and cirrhosis, 4.45kPa) were established. Elevated inflammatory activity and gamma-glutamyltransferase level may affect the diagnostic accuracy of MRE, leading to overestimation of liver fibrosis in early stages. We observed no impact of diabetes, obesity, or any other metabolic disorder on the diagnostic accuracy of MRE.

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.

Prevalence and predictiors of porto-sinusoidal vascular disorder in patients with constantly elevated gamma-glutamyl transferase levels: A multicenter Italian study

Prevalence and predictiors of porto-sinusoidal vascular disorder in patients with constantly elevated gamma-glutamyl transferase levels: A multicenter Italian study

Association between Fasting and Postprandial Levels of Liver Enzymes with Metabolic Syndrome and Suspected Prediabetes in Prepubertal Children.

Elevated liver enzyme activity may be associated with metabolic syndrome (MetS); however, it is not included in the MetS definition for children. Postprandial changes in the levels of biochemistry tests are related to manifestations of metabolic abnormalities. We assessed the association between fasting and postprandial liver enzymes levels with MetS and elevated hemoglobin A1c (HbA1c) in children aged 9-11. The study included 51 girls and 48 boys, all presumably healthy. In all participants' anthropometric indices, fasting glucose, insulin, lipid profile and HbA1c were measured. Enzymes, including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), were assayed in fasting and postprandial states. Individuals were divided into subgroups: with (MetS(+): n = 26); without MetS (MetS(-): n = 73); with HbA1c levels ≤ 5.3% (n = 39); and ≥5.7% (n = 11). Elevated fasting GGT levels were found in 23% of MetS(+) children and rarely in MetS(-) children; increased postprandial GGT was noted in 35% of MetS(+) individuals. Postprandial GGT changes tend to predict MetS (OR = 1.16; p = 0.092). Increased fasting ALT was found rarely in MetS(+) children, but did not occur in MetS(-) children. HbA1c ≥ 5.7% occurred rarely and neither fasting ALT nor GGT were related to elevated HbA1c. However, postprandial change of ALT was a good positive predictor of increased HbA1c (OR = 1.33; p = 0.021). Postprandial GGT performs better as an indicator of metabolic syndrome occurrence, and instead postprandial ALT may predict prediabetes in prepubertal children.

Elevated gamma-glutamyl transpeptidase level is associated with an increased risk of hip fracture in postmenopausal women

The aim of this study was to evaluate the association between gamma-glutamyl transferase (GGT) levels and the risk of hip fracture among middle-aged women by using the Korean National Health Insurance Service claims database from 2002 to 2015. After exclusion of those with any chronic liver disease, heavy alcohol consumption, any missing values required for our analysis, or GGT levels less than 1 or greater than 99 percentile, we classified subjects into three groups according to baseline GGT levels. A total of 127,141 women aged 50 years or older were included for analysis (GGT range: 8–106 U/L). During an average 12.1 years of follow-up, 2758 patients sustained hip fractures (2.17%). Compared with the group in the lowest tertile, the group in the highest tertile had the highest cumulative incidence of hip fracture. One log-unit increase in GGT was associated with a 17% increased risk of hip fracture. Subgroup analysis by BMI (≥ 25 vs. < 25 kg/m2), presence of diabetes, levels of other liver enzymes, and alcohol consumption level did not show significant effect modification. In summary, elevated baseline GGT level was associated with an increased risk of hip fracture in postmenopausal women, independent of alcohol consumption and chronic liver disease.

Elevated gamma-glutamyl transferase levels are associated with stroke recurrence after acute ischemic stroke or transient ischemic attack.

AimsGamma‐glutamyl transferase (GGT) is considered a marker of oxidative stress in vivo. In this study, we aimed to examine the association of serum GGT levels with 3‐month and 1‐year stroke recurrence in patients with acute ischemic stroke or transient ischemic attack (TIA).MethodsWe conducted a large and multicenter cohort study. Participants with ischemic stroke or TIA who had a baseline GGT measurement were enrolled in the China National Stroke Registry‐3 study from August 2015 to March 2018. They were divided into four groups according to sex‐specific quartiles of GGT levels. The effect of GGT on stroke recurrence and other vascular events was examined during the 1‐year follow‐up period. Multivariate Cox regression models were performed to evaluate the association. Discrimination tests were used to examine the degree to which incorporating GGT into the conventional model predicted stroke adverse outcomes.ResultsA total of 12,504 patients were enrolled. At both the 3‐month and 1‐year follow‐ups, patients in the highest quartile group of GGT levels exhibited a higher risk of stroke recurrence [HR 1.32 (95% CI 1.07–1.63), HR 1.34 (95% CI 1.13–1.60)], ischemic stroke [HR 1.37 (95% CI 1.10–1.71), HR 1.37 (95% CI 1.14–1.64)], and combined vascular events [HR 1.34 (95% CI 1.09–1.65), HR 1.34 (95% CI 1.13–1.59)] than those in the lowest quartile group. Moreover, the Kaplan–Meier curves revealed that the incidence rates of stroke adverse outcomes were quite different in the four groups. The highest quartile group showed the highest cumulative incidence, while the lowest quartile group showed the lowest cumulative incidence. After applying discrimination tests, adding GGT into the conventional model resulted in slight improvements in predicting stroke adverse outcomes (NRI: 10%–14%).ConclusionThis study demonstrated that elevated GGT levels were positively associated with an increased risk of stroke adverse outcomes, namely, recurrence, ischemic stroke, and combined vascular events.

FRI272 - High rates of histological findings compatible with porto-sinusoidal vascular disease in patients with constantly elevated gamma-glutamyl transferase levels undergoing a liver biopsy

FRI272 - High rates of histological findings compatible with porto-sinusoidal vascular disease in patients with constantly elevated gamma-glutamyl transferase levels undergoing a liver biopsy

Apparently healthy adults with high serum gamma-glutamyl transferase levels are at increased risk of asthma development in the near future: a Korean nationwide cohort study.

Serum gamma-glutamyl transferase (GGT), an indicator of oxidative stress and/or a chronic inflammatory process, is associated with the levels of leukotrienes and other inflammatory mediators that play a critical role in the pathogenesis of asthma. This study aimed at investigating whether apparently healthy subjects with higher serum GGT levels at a national health check-up are at an increased risk of developing asthma in the near future. We analyzed 564,213 Korean adults, aged 20-80 years who underwent a national general health examination, including measurement of baseline serum GGT between 2003 and 2015, using data from a large-scale representative cohort of the Korean population. Data were analyzed using a Cox proportional hazards regression analysis. In total, 516,956 participants were included in the final analysis. During the mean follow-up period of 8 years (standard deviation, 4.0), 7,439 incident asthma events occurred. We then classified the male and female participants according to quartiles of blood GGT levels (males: ≤ 20, 21-30, 31-51, and ≥ 52 IU/L; females: ≤ 12, 13-16, 17-22, and ≥ 23 IU/L, respectively). The adjusted hazard ratio (aHR) for incident asthma was significantly greater for subjects in the highest GGT quartile than for those in the lowest GGT quartile (aHR, 1.47; 95% confidence intervals, 1.36-1.59). Further, there was a significant linear trend across quartiles with regard to asthma (ptrend<0.001). We estimated the optimal cut-off values (using the minimum p-value approach) as 35 IU/L for the total population, 35 IU/L for males, and 36 IU/L for females, respectively. Clinicians should be aware of the risk of incident asthma in healthy subjects with elevated GGT levels. Our findings advance our understanding of asthma pathogenesis.

Ponatinib in pediatric patients with Philadelphia chromosome-positive leukemia: a retrospective survey of the Japan Children's Cancer Group.

Ponatinib is effective in adults with Philadelphia chromosome-positive (Ph+) leukemia, resistant or intolerant to second-generation tyrosine kinase inhibitors, but there are limited data on its use in children. The clinical courses of nine pediatric patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) and four with chronic myeloid leukemia (CML) who received ponatinib therapy were retrospectively reviewed. The median age at the start of ponatinib therapy was 12years (range 8-16years). Nine patients were male and four were female. Six patients received ponatinib alone, three received ponatinib with prednisolone, one received ponatinib with rituximab intrathecal therapy, and one received ponatinib with conventional chemotherapy. Two patients received ponatinib both alone and in combination with chemotherapy. The median dose and duration of ponatinib were 16.9mg/m2 (7-34.3) and 1.1months (0.2-22.7), respectively. Six patients with Ph+ ALL and two with CML responded to ponatinib. One of the eight patients who received ponatinib alone had grade 4 increased lipase levels. Grade 3 non-hematologic toxicities included elevated alanine aminotransferase levels (25%), elevated aspartate aminotransferase levels (25%), elevated gamma-glutamyl transferase levels (12.5%), hypertension (12.5%), and polymorphic erythema (12.5%). Ponatinib may be safe and effective in pediatric patients with Ph+ leukemia.