Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio is a more powerful marker than TyG index for predicting metabolic syndrome in patients with type 2 diabetes mellitus.

Purpose: The prevalence of metabolic syndrome (MetS) is increasing globally and has become a global and national public health problem that cannot be ignored as an independent predictor of cardiovascular events, cancer and all-cause mortality. γ-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-C) are associated with insulin resistance, dyslipidemia and oxidative stress. This study was designed to explore the relationship and predictive performance between γ-glutamyl transferase high-density lipoprotein cholesterol ratio (GGT/HDL-C) and MetS. Methods: This was a cross-sectional study. MetS was diagnosed from biochemical and anthropometric data in subjects with T2DM. Multivariate logistic regression was used to analyses the relationship between GGT/HDL-C ratio, TyG index and HOMA-IR and MetS in subjects with T2DM. Receiver operating characteristic (ROC) curve was drawn and the areas under the curve (AUC) were used to assess the ability of these indexes in screening MetS in subjects with T2DM. Statistical differences between the AUC values of these indexes were compared. In addition, we performed subgroup analyses and interactions. Results: 769 (70.55%) patients with T2DM were defined as having MetS. patients with MetS had higher anthropometric values and biochemical indicators compared to those without MetS. Multivariate logistic regression analysis of GGT/HDL-C ratio was an independent risk factor for MetS (Per 1 SD increase, OR = 2.49, 95% CI: 1.51, 4.10). According to ROC curve analysis, the value of GGT/HDL-C ratio in predicting MetS in subjects with T2DM was superior to that of TyG index and HOMA-IR. The best cut-off value for GGT/HDL-C prediction was 19.94. Conclusions: GGT/HDL-C ratio may be an important predictor of MetS in subjects with T2DM, and its predictive power is stronger than that of TyG index and HOMA-IR. The risk of MetS in subjects with T2DM is increased in the presence of a higher GGT/HDL-C ratio.

Prognostic value of alkaline phosphatase and gamma-glutamyl transferase in patients with metastatic pancreatic cancer.

Background: Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. This study evaluated the prognostic role of serum alanine phosphatase (ALP) and gamma-glutamyl-transferase (GGT) in metastatic PC patients. Materials & methods: 153 patients with metastatic PC receiving first-line treatment with nab-paclitaxel/gemcitabine were retrospectively enrolled in a multicenter study and stratified according to ALP (≤ or >260 U/l) and GGT (≤ or >45.5 U/l) levels. Results: Improved overall survival was recorded in patients with GGT levels ≤45.5 U/l (p < 0.05). In patients with liver metastasis, overall survival was significantly lower in patients with high ALP (p = 0.01) and GGT (p = 0.02). Conclusion: High levels of ALP and GGT were related to a poor prognosis in PC patients with liver metastasis receiving nab-paclitaxel/gemcitabine.

Pancreatic cancer is a deadly form of cancer. This study looked at whether levels of two enzymes, alanine phosphatase (ALP) and gamma-glutamyl-transferase (GGT), in the blood of patients with metastatic pancreatic cancer could predict how long they would live. The study included 153 patients who were receiving their first treatment for metastatic pancreatic cancer. The patients were divided into groups based on whether their ALP and GGT levels were high or low. The researchers found that patients with low GGT levels tended to live longer. Patients with liver metastasis (spread of cancer to the liver) who had high levels of ALP and GGT tended to have a worse prognosis than patients with low levels of these enzymes. Therefore, higher levels of ALP and GGT in the blood may be associated with a poor prognosis in pancreatic cancer patients with liver metastasis who are receiving nab-paclitaxel/gemcitabine treatment.

Preoperative CA19-9 and GGT ratio as a prognostic indicator in ampullary carcinoma.

BACKGROUND AND AIMS: In recent years, more and more inflammatory indicators have been studied to predict the long-term survival of patients with ampullary carcinoma (AC) after radical resection, but these prognostic indicators are still controversial. Therefore, based on previous inflammation scores, this study established a novel, easily accessible, more feasible and more predictive prognostic marker [Carbohydrate antigen199 to gamma-glutamyltransferase ratio (CA19-9/GGT)] to better assess the prognostic significance in AC patients undergoing radical resection. METHODS: Overall survival (OS) and recurrence-free survival (RFS) were analyzed by Cox regression model. Correlation between CA19-9/GGT and clinicopathological variables were analyzed by Chi-squared test, Fisher ' s exact test, independent sample t test and Mann-Whitney U test. The performance of prognostic indexes is compared by the consistency index (C-index). The prediction accuracy of nomogram is further confirmed by calibration curve and decision curve analysis (DCA). RESULTS: CA19-9/GGT was an independent risk factor affecting OS [P = 0.001, hazard ratio (HR) 2.459, 95% confidence intervals (CI) 1.450-4.167] and RFS (P = 0.002, HR 2.333, 95% CI 1.371-3.971) in multivariate analysis. The optimal cut-off value of CA19-9/GGT was 0.14. In CA19-9/GGT correlation analysis, high risk group (> 0.14) was significantly associated with poor prognosis. The predictive performance of CA19-9/GGT (OS: C-index = 0.753, RFS: C-index = 0.745) was confirmed to be superior to other prognostic indicators according to the C-index. Compared with the simple AJCC staging system, the Nomogram prediction model (OS: C-index = 0.787, RFS: C-index = 0.795) established by the combination of CA19-9/GGT and AJCC 8th TNM staging system has higher prediction accuracy. CONCLUSIONS: CA19-9/GGT was an independent prognostic indicator after radical resection of AC. Incorporating CA19-9/GGT into the AJCC TNM staging system optimized the prediction accuracy of the TNM staging system, and further verified the predictive value of CA19-9/GGT.

Serum Gamma Glutamyltransferase (GGT) in coronary artery disease: Exploring the Asian Indian Connection.

Background: There is a need to identify novel markers for CAD, independent of traditional CV risk factors. One of these is gamma-glutamyl transferase (GGT), a marker of increased oxidative stress. Given the high prevalence of CAD in Asian Indians, the link of GGT and CAD in them needs to be studied. Aim: To assess GGT in patients with angiographically documented CAD. Methods and Results: Two hundred patients aged 58.1 ± 9.95 years, 73% males, hypertension 56%, diabetes 40% were included. Mean GGT was 63.6 ± 44.33 (10-269 U/L). The levels of GGT progressively increased in those with single/double or triple-vessel CAD (36.5, 61.5, and 87 U/L, respectively, P < 0.001). Using objective criteria of CAD burden (SYNTAX and Gensini scores), we reaffirmed these findings. GGT in patients with SYNTAX tertiles 0-22, 23-32, and ≥ 33 was 33, 62, and 97 U/L, respectively and in Gensini tertiles 0-17.65, 17.66-56.65, ≥56.66 was 32, 52, and 88 U/L, respectively, all P < 0.001. SYNTAX score ≥ 23 was present in only 23% patients in GGT tertile 1 (<41 U/L), whereas60% and 94% in GGT tertiles 2 and 3 had SYNTAX ≥ 23. Significant positive correlation was seen between GGT and SYNTAX (r = 0.634) and Gensini score (r = 0.772). Conclusions: In this study, GGT had an independent correlation with angiographic severity of CAD and SYNTAX and Gensini scores. Although the existing evidence seems biologically plausible, more studies are needed to explore the potential role of this inexpensive marker for predicting disease burden in patients with CAD.

Elevated gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio has a non-linear association with incident diabetes mellitus: A second analysis of a cohort study.

OBJECTIVE: Evidence regarding the association between the GGT/HDL-c ratio and incident diabetes is still limited. On that account, our research aims to survey the link of the GGT/HDL-c ratio with the risk of diabetes. METHODS: In this retrospective cohort study, data of 15,171 participants who participated in the medical examination program were collected in Murakami Memorial Hospital in Japan from 2004 to 2015. The independent and dependent variables were the baseline GGT/HDL-c ratio and diabetes during the follow-up, respectively. The Cox proportional-hazards regression model was used to explore the association between the GGT/HDL-c ratio and diabetes risk. A Cox proportional hazards regression with the cubic spline smoothing was used to recognize non-linear relationships between the GGT/HDL-c ratio and incident diabetes. RESULTS: After adjusting covariates, the results showed that the GGT/HDL-c ratio was positively associated with incident diabetes (HR = 1.013, 95% CI: 1.002, 1.024). There was also a non-linear relationship between the GGT/HDL-c ratio and the risk of diabetes, and the inflection point of the GGT/HDL-c ratio was 6.477. The HR on the left and right sides of the inflection point was 2.568 (1.157, 5.699) and 1.012 (1.001, 1.023), respectively. The sensitivity analysis demonstrated the robustness of the results. Besides, the performance of the FPG + GGT/HDL-c ratio was better than FPG + GGT, FPG + HDL-c, and FPG in predicting diabetes. CONCLUSION: This study demonstrates a positive and non-linear relationship between the GGT/HDL-c ratio and incident diabetes in the Japanese population. The GGT/HDL-c ratio is strongly related to diabetes risk when it is <6.477.

Gut microbiome is associated with metabolic syndrome accompanied by elevated gamma-glutamyl transpeptidase in men.

It is predicted that by 2035, metabolic syndrome (MS) will be found in nearly more than half of our adult population, seriously affecting the health of our body. MS is usually accompanied by the occurrence of abnormal liver enzymes, such as elevated gamma-glutamyl transpeptidase (GGT). More and more studies have shown that the gut microbiota is involved in MS; however, the correlation between gut microbiota and MS with elevated GGT has not been studied comprehensively. Especially, there are few reports about its role in the physical examination of the population of men with MS and elevated GGT. By using the whole-genome shotgun sequencing technology, we conducted a genome-wide association study of the gut microbiome in 66 participants diagnosed as having MS accompanied by high levels of GGT (case group) and 66 participants with only MS and normal GGT level (control group). We found that the number of gut microbial species was reduced in participants in the case group compared to that of the control group. The overall microbial composition between the two groups is of significant difference. The gut microbiota in the case group is characterized by increased levels of "harmful bacteria" such as Megamonas hypermegale, Megamonas funiformis, Megamonas unclassified, Klebsiella pneumoniae, and Fusobacterium mortiferum and decreased levels of "beneficial bacteria" such as Faecalibacterium prausnitzii, Eubacterium eligens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides dorei, and Alistipes putredinis. Moreover, the pathways of POLYAMSYN-PWY, ARG+POLYAMINE-SYN, PWY-6305, and GOLPDLCAT-PWY were also increased in the case group, which may play a role in the elevation of GGT by producing amine, polyamine, putrescine, and endogenous alcohol. Taken together, there are apparent changes in the composition of the gut microbiome in men with MS and abnormal GGT levels, and it is high time to discover specific gut microbiome as a potential therapeutic target in that population. More in-depth studies of relevant mechanism could offer some new methods for the treatment of MS with elevated GGT.

Association of Obesity and Serum Gamma Glutamyl Transferase with Impaired Fasting Glucose in Adults at a Tertiary Level Hospital of Bangladesh.

Obesity is a worldwide health concern due to its rising tendency both in developing and developed countries. Obesity is known to be associated with a number of disorders including type 2 diabetes mellitus, hypertension and cardiovascular diseases. Gamma glutamyl transferase (GGT) is synthesized in liver. GGT is considered as an oxidative stress marker. Serum GGT is increased in patients with cardiovascular diseases and diabetes mellitus (DM). Impaired fasting glucose (IFG) is a risk factor for cardiovascular diseases. The aim of this study was to find out the association of obesity and serum GGT with IFG. This cross-sectional analytical study was conducted in the Biochemistry department of Sir Salimullah Medical College, Dhaka from March 2018 to February 2019. The ages of the subjects were 25-55 years. The study subjects were 120 and were divided into two groups. The groups were Normal fasting glucose (NFG) group and IFG group according to WHO diagnostic criteria. Body mass index (BMI) was used as a measure of general obesity and waist circumference (WC) and waist-hip ratio (WHR) were used as measures of abdominal or central obesity. OGTT was performed from collected blood. GGT and lipid profile were measured from serum. In IFG group, BMI, WC, WHR and GGT levels were significantly elevated (p<0.01) than NFG group i.e. BMI (22.70±1.35 vs. 28.37±2.33kg/m²), WC (79.96±5.31 vs. 93.42±4.21cm), WHR (0.92±0.06 vs. 0.97±0.07), and GGT (24.19±8.41 vs. 67.23±14.40U/L). Fasting Plasma Glucose (FPG) level were significantly higher (p<0.01) in obese group than over weight and normal BMI groups 4.70±0.08, 5.30±1.3 and 6.50±0.3 respectively. FPG were higher in male and female obese group than normal WC group (4.8±1.1 vs. 6.3±0.60mmol/L) and (4.4±0.7 vs. 6.2±0.80mmol/L). Odds Ratio (OR) and (95% CI) for IFG were 6.53 and 21.0 with BMI tertile 2(23.1- 27.5kg/m²) and tertile 3(≥27.5kg/m²) where T1 (<23.0kg/m²) was considered as reference category. OR for IFG were 4.1 and 20.25 with GGT tertile 2(24.0-42.0) U/L and tertile 3(>42.0) U/L where T1 (<24.0) U/L was considered as reference category. Multiple regression analysis shows positive correlation of FPG with BMI, WC, WHR and GGT.

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.

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cross-sectional association between gamma-glutamyl transferase and hyperuricaemia: the China Multi-Ethinic Cohort (CMEC) study.

OBJECTIVES: Several studies have demonstrated the association between gamma-glutamyl transferase (GGT) and hyperuricaemia, but little is known about such relation in less-developed ethnic minority regions. DESIGN: We cross-sectionally analysed data from the China Multi-Ethnic Cohort (Yunnan region). SETTING: Cross-sectional study. PARTICIPANTS: 22 020 participants aged 30-79 years from Han ethnicity, Yi ethnicity and Bai ethnicity. OUTCOMES: The serum level of uric acid, GGT and other metabolic parameters were tested. Weight, height and blood pressure were measured. Smoking, drinking, ethnicity, education and medical history were obtained from questionnaires. RESULTS: In the crude model, compared with the lowest quintile, the second, third, fourth and fifth quintiles of serum GGT exhibited a positive association with hyperuricaemia risk (OR=1.69, 2.90, 4.34 and 7.70, 95% CI=1.42 to 2.01, 2.47 to 3.42, 3.71 to 5.09 and 6.60 to 8.98, respectively, p-trend<0.0001). In fully adjusted model, compared with the lowest quintile, the second, third, fourth and fifth quintiles of serum GGT also exhibited a positive association with hyperuricaemia risk (OR=1.26, 1.68, 2.02 and 3.02, 95% CI=1.04 to 1.51, 1.40 to 2.00, 1.69 to 2.42 and 2.51 to 3.64, respectively, p-trend<0.0001). Logistic regression model was conducted separately in ethnic groups. Compared with first quintile, the highest GGT level were related to higher risk of hyperuricaemia in three ethnic groups (OR (95% CI): 2.89 (2.26 to 3.68), 2.81 (1.93 to 4.11) and 3.04 (1.91 to 4.84) for Han, Yi and Bai ethnicity, respectively, p-trend <0.0001). The relationship between GGT and hyperuricaemia was also observed in different age groups or gender groups. CONCLUSIONS: High serum GGT level was related to a higher risk of hyperuricaemia in less-developed ethnic minority regions in China.

Prevalence and associations of metabolic syndrome in patients with alcohol use disorder.

Excessive alcohol consumption has been associated with different components of the metabolic syndrome (MetS) such as arterial hypertension, dyslipidemia, type 2 diabetes or obesity. We aimed to analyze the prevalence and associations of MetS in patients with Alcohol Use Disorder (AUD). Cross-sectional study in heavy drinkers admitted for the treatment of AUD between 2013 and 2017. Medical comorbidity, anthropometric data, alcohol use and biological parameters were obtained. MetS was established according to the harmonized definition. A total of 728 patients (22% women) were included; median age was 47 years (IQR: 40-53.5), median alcohol consumption was 160 g/day (IQR: 115-240) and prevalence of MetS was 13.9%. The multivariate analysis showed a significant dose-response effect of estimated glomerular filtration (eGFR) and MetS: relative to patients with eGFR > 90 mL/min, those with eGFR (60-90 mL/min) and those with eGFR < 60 mL/min were 1.93 times (95% CI 1.18-3.15) and 5.61 times (95% CI 1.66-19.0) more likely to have MetS, respectively. MetS was significantly associated with hyperuricemia (OR 2.28, 95% CI 1.36-3.82) and elevated serum GGT (OR 3.67, 95% CI 1.80-7.46). Furthermore, for every increase of 1 year in age, the probability of MetS increased significantly (OR 1.03, 95% CI 1.01-1.05). MetS in heavy drinkers is independently associated with reduced kidney function and metabolic risk factors including hyperuricemia and elevated serum GGT.

Effect of growth hormone therapy on liver enzyme and other cardiometabolic risk factors in boys with obesity and nonalcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most common causes of liver disease in children and adolescents. Although several reports have confirmed the significant correlation between NAFLD and growth hormone (GH)-insulin-like growth factor 1(IGF-1) axis, no study further investigates whether or not recombinant human GH (rhGH) treatment can improve NAFLD in obese children. METHODS: This study was a randomized, open-label study comprising 44 boys with obesity and NAFLD (11.76 ± 1.67 year) to evaluate the effects of 6 months of rhGH administration for boys with obesity and NAFLD. The subjects were randomized divided into treatment group (subjects with recombinant human GH (rhGH)) and control group for 6 months. RESULTS: After 6 months, IGF-1 increased significantly during rhGH treatment, in comparison with the control group (582.45 ± 133.00 vs. 359.64 ± 129.00 ng/ml; p < 0.001). A significant reduction in serum alanine aminotransferase(ALT) (15.00 vs. 28.00 U/L; p = 0.001), aspartate aminotransferase(AST) (20.00 vs. 24.50U/L; p = 0.004), gamma glutamyl transferase(GGT) (14.50 vs. 28.50 U/L; p < 0.001) was observed in the GH-treated boys. In addition, the rhGH group showed a significant decrease in C reactive protein (CRP) (1.17 ± 0.76 vs. 2.26 ± 1.43 mg/L) and body mass index standard deviation scores (BMI SDS) (2.28 ± 0.80 vs. 2.71 ± 0.61) than the control group (p = 0.003, p = 0.049 respectively). GH treatment also reduced low density lipoprotein cholesterol (LDL-C) (2.19 ± 0.42 vs. 2.61 ± 0.66 mmol/L; p = 0.016) and increased high density lipoprotein cholesterol (HDL-C) (1.30 vs. 1.15 mmol/L; p = 0.005), and there were no changes in total cholesterol (TC), triglycerides (TG) and uric acid(UA) between the treatment group and the control group. CONCLUSION: Our findings suggest that 6 months treatment with rhGH may be beneficial for liver enzyme and can improve obesity-related other cardiovascular and metabolic complications in boys with obesity and NAFLD.

The association between elevated lipid profile and liver enzymes: a study on Bangladeshi adults.

Dyslipidemia, a major contributor to cardiovascular diseases, is rapidly increasing in Asian countries including Bangladesh. In addition to the cardiovascular system, abnormal lipid levels are also known to cause complications in renal and hepatic systems. The data regarding dyslipidemia and its relationship with liver enzymes are scarce for the Bangladeshi population. Therefore, this study was conducted to estimate the prevalence of dyslipidemia and determine the relationship between lipid profile and liver enzymes in Bangladeshi adults. A total of 405 participants (318 males and 87 females) were enrolled in the study. Serum levels of TG, TC, LDL, HDL and liver enzymes including ALT, AST, GGT and ALP were analyzed using standard methods. Dyslipidemia and liver function tests abnormalities were defined according to the international standard guidelines. The association between elevated lipid profile markers and liver enzyme abnormalities was assessed by logistic regression analysis. Overall, the prevalence of elevated TG, TC, LDL and low HDL were 30.9%, 23.7%, 26.2% and 78.8%, respectively. On the other hand, the prevalence of elevated liver enzymes ALT, AST, GGT and ALP were 18.8%, 21.6%, 12.9% and 21.9%, respectively. Dyslipidemia and liver enzyme abnormalities were higher in diabetic and hypertensive participants than in the healthy participants. About 61% of participants with dyslipidemia had at least one or more elevated liver enzymes. In regression analysis, an independent association was observed between serum GGT and all lipid components. In conclusion, a high prevalence of dyslipidemia and liver enzyme abnormalities were observed among the study participants. Of the four liver enzymes, the serum levels of GGT showed an independent association with all lipid components. Moreover, this study indicates that subjects with dyslipidemia often have a higher chance of having liver diseases than subjects with no dyslipidemia. However, large-scale prospective studies are needed to understand the underlying mechanisms of lipid-induced hepatic dysfunction in the Bangladeshi population.

Camrelizumab plus apatinib as second-line treatment for advanced oesophageal squamous cell carcinoma (CAP 02): a single-arm, open-label, phase 2 trial.

BACKGROUND: Camrelizumab, an anti-PD-1 antibody, has shown moderate efficacy in oesophageal squamous cell carcinoma. Apatinib, a selective inhibitor of VEGFR2, has a synergistic effect with immunotherapy. We aimed to assess the combination of camrelizumab and apatinib as second-line treatment for advanced oesophageal squamous cell carcinoma. METHODS: This single-arm, open-label, phase 2 study was conducted at eight centres in China. Eligible patients were aged 18-75 years, with an Eastern Cooperative Oncology Group performance status of 0 or 1, who had unresectable locally advanced, locally recurrent, or metastatic oesophageal squamous cell carcinoma, and had progressed after or were intolerant to first-line chemotherapy. Patients received intravenous camrelizumab 200 mg once every 2 weeks plus oral apatinib 250 mg once daily for a 28-day cycle until disease progression, unacceptable adverse events, or withdrawal of consent. The primary endpoint was investigator-assessed confirmed objective response rate. Efficacy was analysed in patients who had received at least one dose of study drug, and safety was analysed in patients who received the study drug and had at least one post-baseline safety assessment. The study of this cohort is complete and this trial is registered with ClinicalTrials.gov, number NCT03736863. FINDINGS: Between Dec 5, 2019, and Feb 10, 2021, 52 patients were enrolled and included in analyses. At data cutoff (June 20, 2021), median follow-up was 7·5 months (IQR 4·0-11·2). 18 (34·6%, [95% CI 22·0-49·1]) of 52 patients had a confirmed objective response. 23 (44%) of 52 patients had grade 3 or worse treatment-related adverse events. The most common grade 3 or worse treatment-related adverse events were increased aspartate aminotransferase (10 [19%]), increased gamma-glutamyltransferase (10 [19%]), and increased alanine aminotransferase (five [10%]). No treatment-related deaths occurred. INTERPRETATION: Camrelizumab combined with apatinib showed promising activity and manageable toxicity, and might be a potential second-line treatment option for patients with advanced oesophageal squamous cell carcinoma. Another cohort of this study, enrolling patients previously treated with first-line immunotherapy, is ongoing. FUNDING: Jiangsu Hengrui Pharmaceuticals.

Characteristics of peripheral blood Gamma-glutamyl transferase in different liver diseases.

ABSTRACT: Gamma-glutamyl transferase (GGT) is a marker of oxidative stress and cholestasis. Because of its low specificity, clinicians usually ignore its diagnostic value.To compare and analyze the clinical features of GGT in primary biliary cholangitis (PBC), drug-induced liver injury (DILI), alcoholic liver disease (ALD), and non-alcoholic fatty liver disease (NAFLD) from the perspective of different causes instead of the severity of the disease.We observed the distribution characteristics and the rate of abnormality of GGT in the above 4 diseases. The relationship between GGT and alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total serum bilirubin, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol was analyzed using Spearman correlation.The highest level of GGT was up to 1000.00 to 2000.00 U/L in PBC and DILI, and the highest level of GGT was more than 2000.00 U/L in ALD, yet the difference was not statistically significant (P > .05). The highest level of GGT was only about 200.00 U/L in NAFLD and was the lowest in 4 liver diseases. Also, GGT was positively correlated with ALP, TC in PBC and DILI. Also, in ALD, GGT was positively correlated with ALT, AST, ALP, TG, and TC. In NAFLD, GGT was positively correlated with ALT, AST, and TG.The abnormal GGT in PBC and cholestasis DILI was associated with cholestasis; in ALD, it was associated with oxidative stress and cholestasis, and in NAFLD, it was associated with oxidative stress. GGT levels had different characteristics in different liver diseases, which were closely related to the pathogenesis of liver diseases.

Sex difference in the associations among liver function parameters with incident diabetes mellitus in a large Taiwanese population follow-up study.

Background: The prevalence of diabetes mellitus (DM) in Taiwan between 2017 and 2020 was 11.05%, which is higher than the global prevalence (10.5%). Previous studies have shown that patients with DM have higher liver enzyme levels than those without DM. However, it is unclear whether there are sex differences in the association between incident DM and liver function. Therefore, the aim of this longitudinal study was to investigate this issue in a large Taiwanese cohort. Methods: We identified 27,026 participants from the Taiwan Biobank, and excluded those with baseline DM (n = 2,637), and those without follow-up data on DM, serum fasting glucose or glycosylated hemoglobin A1c (n = 43). The remaining 24,346 participants (male: 8,334; female: 16,012; mean age 50.5 ± 10.4 years) were enrolled and followed for a median of 4 years. Results: Of the enrolled participants, 1,109 (4.6%) had incident DM and 23,237 (95.4%) did not. Multivariable analysis showed that high levels of glutamic-oxaloacetic transaminase (AST) (p < 0.001), glutamic-pyruvic transaminase (ALT) (p < 0.001), albumin (p = 0.003), α-fetoprotein (p = 0.019), and gamma-glutamyl transpeptidase (GGT) (p = 0.001) were significantly associated with incident DM in the male participants. In comparison, high levels of AST (p = 0.010), ALT (p < 0.001), albumin (p = 0.001) and GGT (p < 0.001), and low total bilirubin (p = 0.001) were significantly associated with incident DM in the female participants. There were significant interactions between total bilirubin and sex (p = 0.031), and GGT and sex (p = 0.011) on incident DM. Conclusion: In conclusion, liver function parameters were significantly associated with incident DM. Further, there were differences in the associations between the male and female participants.

Gamma-glutamyl transferase and cardiovascular events in patients with congenital heart disease.

INTRODUCTION: Serum gamma-glutamyl transferase activity (GGT) seems to predict cardiovascular events in different populations. However, no data exist on patients with congenital heart disease (CHD). METHODS: Observational, analytic, prospective cohort study design involving CHD patients and a control population to determine the effect of GGT levels on survival. RESULTS: A total of 589 CHD patients (58% males, 29 ± 14 years old) and 2745 matched control patients were followed up. A total of 69 (12%) CHD patients had a major acute cardiovascular event (MACE) during the follow-up time (6.1 [0.7-10.4] years). Patients with CHD and a GGT >60 U/L were significantly older, more hypertensive and dyslipidemic, had a worse NYHA functional class and a greater anatomical complexity than CHD patients with a GGT ≤60 U/L. The binary logistic regression analysis showed that age, a great CHD anatomical complexity, and having atrial fibrillation/flutter were the predictive factors of higher GGT levels (>60 U/L). The Kaplan-Meier analysis showed that patients with CHD and a GGT concentration above 60 UL showed the lowest probability of survival compared to that of CHD with GGT ≤60 U/L and controls irrespective of their GGT concentrations (p < .001). Similarly, the multivariable Cox regression analysis found an independent association between higher GGT levels (>60 U/L) and a worse prognosis (HR 2.44 [1.34-4.44], p = .003) among patients with CHD. CONCLUSION: Patients with CHD showed significant higher GGT levels than patients in the control group having those with higher GGT concentrations (>60 U/L) the worst survival.

The alcohol marker phosphatidylethanol is closely related to AST, GGT, ferritin and HDL-C.

BACKGROUND: The aim of this study was to evaluate the quantitative relation between common clinical chemical analyses and ethanol use, measured by a combination of the two alcohol markers phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT). METHODS: Results of PEth and CDT in whole blood and serum, respectively, were included, together with information on 10 different commonly measured clinical chemical analytes, as well as age and sex. PEth was analysed by UPC2 -MS/MS and CDT was measured by capillary electrophoresis. RESULTS: Samples from 4873 patients were included. The strongest relation to alcohol consumption as measured by PEth, when correcting for age and sex, was found for HDL-C (standardized ß = 0.472, p < 0.001), AST (standardized ß = 0.372, p < 0.001), ferritin (standardized ß = 0.332, p < 0.001) and GGT (standardized ß = 0.325, p < 0.001). The relation to PEth was weak for total cholesterol, TG and ALP. No relation was found for Hb and LDL-C. CONCLUSIONS: When using PEth as a marker for alcohol consumption, this study demonstrated the quantitative relation to commonly used test as AST or GGT, but also an important relation to ferritin or HDL-C. In clinical practice, elevated levels of these clinical chemical analytes should initiate further work-up on possibly harmful alcohol use.

A Multiple Logistic Regression Model Based on Gamma-Glutamyl Transferase as a Biomarker for Early Prediction of Drug-Induced Liver Injury in Vietnamese Patients.

The discovery of new biomarkers and the causality of drug-induced liver injury (DILI) is a major focus in modern medicine. Alcoholism is considered a risk factor for DILI. However, the extraction and assessment of alcohol history are difficult due to noncooperation by patients and intermittent management. Therefore, we conducted a case-control study of 1277 patients diagnosed with DILI according to the Roussel Uclaf Causality Assessment Method scale to evaluate gamma-glutamyl transferase (GGT) as a biomarker for predicting DILI in Vietnamese patients, where the proportion of alcoholism is quite high. Further, we built and validated a logistic regression model to predict the risk of DILI in hospitalized patients. The risk of DILI increased by 10% for 1 UI/L higher levels of GGT before prescription (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.01). A history of alcoholism was not a risk factor for DILI occurrence (OR, 1.83; 95%CI, 0.99-3.04; P = .057). A logistic regression model was successfully built and validated based on age; sex; initial levels of alanine aminotransferase, alkaline phosphatate, GGT, likelihood score of the suspected drug, and history of liver disease; the area under the receiver operating characteristic curve of the model was 0.883 (95%CI, 0.868-0.897). Our results thus suggest the necessity of exercising caution when prescribing to patients without a history of alcoholism but having high GGT levels. This model can be applied clinically to assess the risk of DILI before prescribing to reduce the risk of DILI in the patient.

A model incorporating serum C3 complement levels may be useful for diagnosing biliary atresia in infants.

INTRODUCTION: Correctly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants. PATIENTS AND METHODS: The data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups. RESULTS: A total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3+ T cells, CD3+CD4+ T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P<0.05). Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with γ-GT in the BA group, but not in the CC group. Five indices were found to be significantly associated with BA: stool color, globulin, γ-GT, C3 and C4. A model incorporating stool color, gamma-glutamyl transpeptidase level, and C3 level exhibited an area under the ROC curve (AUC) of 0.93, and a sensitivity of 93% and specificity of 83% for the diagnosis of BA. CONCLUSIONS: Models incorporating serum C3 levels may be useful for accurately diagnosing BA in infants.

Investigating the pathogenesis of high-serum gamma-glutamyl transferase activity in Thoroughbred racehorses: A series of case-control studies.

BACKGROUND: High-serum γ-Glutamyl Transferase (GGT) activity has been associated with and thought to be a marker of maladaptation to training and possibly poor performance in racehorses, but the cause is unknown. OBJECTIVES: To investigate possible metabolic and infectious causes for the high GGT syndrome. STUDY DESIGN: Pilot case-control study and nested case-control study. METHODS: The case-control study in 2017 included 16 horses (8 cases and 8 controls with median [range] serum GGT 82 [74-148] and 22 [19-28] IU/L, respectively) from the same stable. In 2018, similar testing was performed in a nested case-control study that identified 27 case (serum GGT 50 ≥ IU/L)-control pairs from three stables for further testing. Serum liver chemistries, selenium measurements, viral PCR and metabolomics were performed. RESULTS: No differences were found in frequency of detection of viral RNA/DNA or copy numbers for equine hepacivirus (EqHV) and parvovirus-hepatitis (EqPV-H) between cases and controls. Mild increases in hepatocellular injury and cholestatic markers in case vs control horses suggested a degree of liver disease in a subset of cases. Metabolomic and individual bile acid testing showed differences in cases compared with controls, including increased abundance of pyroglutamic acid and taurine-conjugated bile acids, and reduced abundance of Vitamin B6. Selenium concentrations, although within or above the reference intervals, were also lower in case horses in both studies. MAIN LIMITATIONS: Observational study design did not allow us to make causal inferences. CONCLUSIONS: We conclude that high GGT syndrome is likely a complex metabolic disorder and that viral hepatitis was not identified as a cause for this syndrome in this cohort of racehorses. Our results support a contribution of oxidative stress and cholestasis in its pathophysiology.