Gamma-glutamyl Transpeptidase Research Articles

Efficacy and Safety of GLP-1 Receptor Agonists in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a major global health challenge. glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown potential therapeutic benefits for MASLD patients, including improvements in liver function, inflammation, and fibrosis. This study aims to systematically review and meta-analyze randomized controlled trials (RCTs) to evaluate the efficacy and safety of GLP-1RAs in MASLD patients, focusing on hepatic outcomes, cardiovascular outcomes, anthropometric measurements, and mortality. Following PRISMA guidelines, a comprehensive database search was conducted to include RCTs assessing GLP-1RAs' effects on MASLD. Quality assessment was conducted using the Revised Cochrane Risk of Bias tool. Our meta-analysis used a random-effects model, calculating standardized mean differences for continuous outcomes to determine the agents' efficacy and safety. Additionally, funnel plots were generated to assess publication bias, ensuring the integrity of our meta-analytical findings. The review included 27 trials, revealing GLP-1RAs significantly improved hepatic function markers (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and liver fat content) and cardiovascular risk factors (fasting blood sugar, HbA1c levels, lipid profiles). Additionally, GLP-1RAs were associated with significant reductions in body weight, BMI, subcutaneous fat, and waist circumference. GLP-1RAs demonstrate a promising therapeutic role in managing MASLD, offering benefits that extend to improving liver function, mitigating cardiovascular risk, and promoting weight loss. Further research is needed to confirm these findings and optimize GLP-1RAs' usage in MASLD treatment.

A 5-Year Mortality Prediction Model for Prostate Cancer Patients Based on the Korean Nationwide Health Insurance Claims Database.

Prostate cancer is the fourth most common cancer and eighth leading cause of cancer-related mortality worldwide. Its incidence is increasing in South Korea. This study aimed to investigate a predictive model for the 5-year survival probability of prostate cancer patients in a Korean primary care setting. This retrospective study used data from the nationwide insurance claims database. The main outcome was survival probability 5 years after the initial diagnosis of prostate cancer. Potential confounding factors such as age, body mass index (BMI), blood pressure, laboratory results, lifestyle behaviors, household income, and comorbidity index were considered. These variables were available in the national health check-up information. A Cox proportional hazards regression model was used to develop the predictive model. The predictive performance was calculated based on the mean area under the receiver operating characteristic curve (AUC) after 10-fold cross-validation. The mean 5-year survival probability was 82.0%. Age, fasting glucose and gamma-glutamyl transferase levels, current smoking, and multiple comorbidities were positively associated with mortality, whereas BMI, alkaline phosphatase levels, total cholesterol levels, alcohol intake, physical activity, and household income were inversely associated with mortality. The mean AUC after 10-fold cross-validation was 0.71. The 5-year survival probability model showed a moderately good predictive performance. This may be useful in predicting the survival probability of prostate cancer patients in primary care settings. When interpreting these results, potential limitations, such as selection or healthy user biases, should be considered.

The efficacy and safety of a novel PD-1/CTLA-4 bispecific antibody cadonilimab (AK104) in advanced non-smallcell lung cancer: A multicenter retrospective observational study.

For patients with advanced non-small cell lung cancer (NSCLC) who have received frontline immunochemotherapy, subsequent treatment options are limited. As the first dual programmed cell death-1 (PD-1)/cytotoxic T lymphocyte-associated antigen-4 bispecific antibody approved globally, cadonilimab demonstrated potential antitumor activity in advanced NSCLC patients resistant to anti-PD-1/PD-L1 antibodies. We retrospectively collected efficacy and safety data from advanced NSCLC patients treated with cadonilimab-based regimens in later therapy lines. A total of 41 advanced NSCLC patients refractory to anti-PD-1/PD-L1 therapy were enrolled. More than half of the patients received cadonilimab-based regimen as a fourth or later line of treatment. At the data cutoff date, treatment efficacy could be evaluated in 23 patients. One patient (4.3%) achieved partial response, eight patients (34.8%) experienced stable disease, and 14 patients (60.9%) progressed. The objective response rate and disease control rate were 4.3% and 39.1%, respectively. The median progression-free survival for all evaluated patients was 108.0 days. Due to the short follow-up period, the median overall survival has not yet been reached. Treatment-related adverse events (TRAEs) and immune-related AEs occurred in 63.4% and 22% patients, respectively. The most common TRAEs included gamma-glutamyl transferase elevation (17.1%), coughing (14.6%), and fatigue (12.2%). Five patients (12.2%) experienced grade ≥3 TRAEs. In this heavily pretreated cohort of advanced NSCLC patients, cadonilimab-based regimens showed moderate antitumor efficacy with a generally tolerable and manageable safety profile. However, more evidence is needed to support the administration of cadonilimab in NSCLC patients refractory to previous anti-PD-1/PD-L1 therapy.

Association of serum gamma-glutamyl transferase levels with cardiovascular disease risk in type 2 diabetes patients: a prospective cohort study

To investigate the associations of serum gamma-glutamyl transferase (GGT) levels with the risk of cardiovascular disease (CVD) and its subtypes in patients with type 2 diabetes mellitus (T2DM) in Jiangsu Province. Methods: The participants were enrolled in the Comprehensive Research project regarding 'Prevention and Control of Diabetes' in Jiangsu Province. The baseline survey was conducted from 2013 to 2014, and follow-up until December 31, 2021. After excluding the participants who self-reported with chronic liver disease/stroke/coronary heart disease at baseline survey and those with incomplete information on GGT, a total of 16 147 T2DM patients were included in the final analysis. Cox proportional hazard regression models were used to calculate the hazard ratio (HR) and their 95%CI of GGT for CVD, myocardial infarction, and stroke. Restricted cubic spline models were applied to analyze the dose-response relationship between GGT and the risk of CVD and its subtypes. Results: During the median follow-up time of 8.02 years, 2 860 CVD cases were registered, including 196 cases of myocardial infarction and 2 730 cases of stroke. Multivariate Cox proportional risk regression model indicated that compared to the lowest serum GGT level group, the highest GGT level group had a 24% increased risk of CVD (HR=1.24, 95%CI: 1.09-1.41) and a 23% increased risk of stroke (HR=1.23, 95%CI: 1.08-1.40). The restricted cubic spline model showed a nonlinear dose-response relationship between GGT and the risk of CVD, myocardial infarction, and stroke in T2DM patients. Conclusions: High levels of GGT may be associated with an increased risk of cardiovascular disease in T2DM patients, which needs further exploration and validation in future clinical practice.

The Association between Fatty Liver Index and Lower Limb Arterial Calcification in Patients with Type 2 Diabetes Mellitus.

Peripheral arterial calcification is a prevalent condition in patients with type 2 diabetes mellitus (T2DM), resulting in lower-limb amputation and reduced life quality. Non-alcoholic fatty liver disease (NAFLD), which can be simply evaluated using the fatty liver index (FLI), is closely associated with T2DM development. In this study, we aimed to explore the relationship between FLI and lower limb arterial calcification (LLAC) in T2DM patients and to reveal the value of T2DM patients with NAFLD in predicting the occurrence of LLAC. A total of 77 T2DM patients with LLAC who underwent comprehensive physical and health examinations, serological examinations, as well as lower limb computed tomography imaging at Sun Yat-sen Memorial Hospital of Sun Yat-sen University between January 2018 and January 2019 were enrolled in this study. The FLI was calculated using body mass index, waist circumference, triglycerides, and γ-glutamyl transferase. Additionally, LLAC was evaluated using computed tomography with the Agatston scoring algorithm. The patients were divided into three groups based on their FLI values: Non-liver disease group (FLI <30, n = 29), borderline-liver disease group (30 ≤ FLI < 60, n = 32), and NAFLD group (FLI ≥60, n = 16). Univariate and multivariate binary logistic regression analyses were employed to investigate the association between FLI and LLAC in T2DM patients. Furthermore, differences in LLAC among groups were analyzed using post-hoc multiple comparisons and ordinal logistic regression model analysis. Univariate and multivariate analyses showed that age and FLI influenced LLAC severity in T2DM patients. Moreover, T2DM patients in the NAFLD group had significantly lower LLAC scores than those in the Non-liver disease group. The correlation analysis showed that FLI was negatively associated with LLAC scores (R = -0.31, p = 0.006), while age was positively associated (R = 0.361, p = 0.001). Our study revealed an inverse relationship between FLI and the degree of LLAC. This indicates that, based on evidence in the current research, NAFLD may not be reliable as a predictor of LLAC in T2DM patients.

Serum liver enzymes and risk of stroke: Systematic review with meta-analyses and Mendelian randomization studies.

Previous observational studies have identified correlations between liver enzyme levels and stroke risk. However, the strength and consistency of these associations vary. To comprehensively evaluate the relationship between liver enzymes and stroke risk, we conducted meta-analyses complemented by Mendelian randomization (MR) analyses. Following the PRISMA guidelines, we performed meta-analyses of prospective studies and conducted subgroup analyses stratified by sex and stroke subtype. Subsequently, adhering to the STROBE-MR guidelines, we performed two-sample bidirectional univariable MR (UVMR) and multivariable MR (MVMR) analyses using the largest genome-wide association studies summary data. Finally, the single-nucleotide polymorphisms associated with liver enzymes on sex differences underwent gene annotation, gene set enrichment, and tissue enrichment analyses. In the meta-analyses of 17 prospective studies, we found the relative risks for serum γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were 1.23 (95% CI: 1.16-1.31) and 1.3 (95% CI: 1.19-1.43), respectively. Subgroup analyses revealed sex and stroke subtype differences in liver enzyme-related stroke risk. Bidirectional UVMR analyses confirmed that elevated GGT, alanine aminotransferase, and aspartate aminotransferase levels were associated with increased stroke occurrence. The primary results from the MVMR analyses revealed that higher ALP levels significantly increased the risk of stroke and ischemic stroke. Gene set and tissue enrichment analyses supported genetic differences in liver enzymes across sexes. Our study provides evidence linking liver enzyme levels to stroke risk, suggesting liver enzymes as potential biomarkers for early identification of high-risk individuals. Personalized, sex-specific interventions targeting liver enzymes could offer new strategies for stroke prevention.

Advancing non-alcoholic fatty liver disease prediction: a comprehensive machine learning approach integrating SHAP interpretability and multi-cohort validation.

Non-alcoholic fatty liver disease (NAFLD) represents a major global health challenge, often undiagnosed because of suboptimal screening tools. Advances in machine learning (ML) offer potential improvements in predictive diagnostics, leveraging complex clinical datasets. We utilized a comprehensive dataset from the Dryad database for model development and training and performed external validation using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 cycles. Seven distinct ML models were developed and rigorously evaluated. Additionally, we employed the SHapley Additive exPlanations (SHAP) method to enhance the interpretability of the models, allowing for a detailed understanding of how each variable contributes to predictive outcomes. A total of 14,913 participants were eligible for this study. Among the seven constructed models, the light gradient boosting machine achieved the highest performance, with an area under the receiver operating characteristic curve of 0.90 in the internal validation set and 0.81 in the external NHANES validation cohort. In detailed performance metrics, it maintained an accuracy of 87%, a sensitivity of 92.9%, and an F1 score of 0.92. Key predictive variables identified included alanine aminotransferase, gammaglutamyl transpeptidase, triglyceride glucose-waist circumference, metabolic score for insulin resistance, and HbA1c, which are strongly associated with metabolic dysfunctions integral to NAFLD progression. The integration of ML with SHAP interpretability provides a robust predictive tool for NAFLD, enhancing the early identification and potential management of the disease. The model's high accuracy and generalizability across diverse populations highlight its clinical utility, though future enhancements should include longitudinal data and lifestyle factors to refine risk assessments further.

Potential impact of ezetimibe on patients with NAFLD/NASH: a meta-analysis of randomized controlled trials.

Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease. Studies have found that ezetimibe may be utilized as a supplemental treatment for NAFLD. Additionally, many clinical trials reported the potential impacts of ezetimibe on patients with NAFLD, although some conclusions remain controversial. Therefore, this study aimed to evaluate the effects of ezetimibe on patients with NAFLD. Online search was conducted across databases including PubMed, Embase, Scopus, Web of Science, Cochrane Library, Wanfang, VIP, and CNKI to retrieve all relevant controlled studies on the treatment of NAFLD with ezetimibe from the inception of the databases until April 2024. This meta-analysis comprised 10 randomized controlled trials (RCTs). Statistical analysis was conducted using the Meta package in R v4.3.2. A total of ten RCTs were included in this study, encompassing 578 patients (290 in the ezetimibe group and 288 in the control group) diagnosed with NAFLD/non-alcoholic steatohepatitis (NASH). The results indicated that ezetimibe significantly reduced levels of aspartate aminotransferase (P < 0.01), glutamyl transferase (γ-GT) (P < 0.01), total cholesterol (P < 0.01), low-density lipoprotein cholesterol (P < 0.01), high-sensitivity C-reactive protein (P < 0.01), and interleukin-6 (P < 0.01), and markedly increased levels of glycated hemoglobin (P = 0.02). Ezetimibe may partially improve transaminase levels and positively impact liver function in patients with NAFLD/NASH. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023461467.

Presence of cholestasis and its impact on survival in SARS-CoV-2 associated acute respiratory distress syndrome.

Data on cholestasis and biliary injury in patients with COVID-19 are scarce. The primary aim of this study was to evaluate the prevalence of cholestasis and factors associated with its development and outcome in critically ill patients with COVID-19 associated acute respiratory distress syndrome (ARDS). In this retrospective exploratory study, COVID-19 patients with ARDS admitted to an intensive care unit (ICU) at the Medical University of Vienna were evaluated for the development of cholestasis defined as an alkaline phosphatase level of 1.67x upper limit of normal for at least three consecutive days. Simple and multiple logistic regression analysis was used to evaluate parameters associated with development of cholestasis and survival. Of 225 included patients 119 (53%) developed cholestasis during ICU stay. Patients with cholestasis had higher peak levels of alkaline phosphatase, gamma-glutamyl transferase, bilirubin and inflammation parameters. Factors independently associated with cholestasis were extracorporeal membrane oxygenation support, ketamine use, high levels of inflammation parameters and disease severity. Presence of cholestasis and peak ALP levels were independently associated with worse ICU and 6-month survival. Development of cholestasis is a common complication in critically ill COVID-19 patients and represents a negative prognostic marker for survival. It is associated with disease severity and specific treatment modalities of intensive care.

Factors Associated with IgG/IgM Levels after SARS-CoV-2 Vaccination in Patients with Head and Neck Cancer.

This study evaluated the factors influencing IgG/IgM antibody levels in 120 patients with head and neck cancer (HNC) following vaccination with inactivated SARS-CoV-2 vaccines. Each patient's demographic and clinical data were documented, and serum IgG and IgM antibodies were detected using a commercial magnetic chemiluminescence enzyme immunoassay kit. The results indicated that while all patients had received at least one vaccine dose, 95 tested positive for IgG and 25 were negative. A higher proportion of IgG-positive patients had received three vaccine doses. Comparatively, gamma-glutamyl transferase levels were elevated in IgM-negative patients. The study further differentiated patients based on their treatment status: 46 were treatment-naive and 74 had received chemotherapy combined with immune checkpoint inhibitors (ICT) at enrollment. Despite similar baseline characteristics and time from vaccination to antibody detection, IgM positivity was significantly lower in the ICT group, with no significant difference in IgG positivity between the treatment-naive and ICT groups. A multivariable analysis identified the number of vaccine doses as an independent factor of IgG positivity, while ICT emerged as an independent risk factor for IgM positivity. Additionally, IgG titers generally declined over time, although patients with higher baseline IgG levels maintained higher titers longer. In conclusion, ICT in patients with HNC does not significantly affect IgG levels post-vaccination. However, booster vaccinations have been shown to be associated with higher IgG positivity, although these levels gradually decrease over time.

Clinical Findings, Laboratory Results, Electrocardiography and Echocardiography Findings in Dairy Buffaloes with Theileriosis.

Tropical theileriosis is a tick-borne haemoprotozoan disease, and cardiac function assessment in buffaloes with theileriosis was poorly documented. The Present study was carried out from April 2022 to December 2022. Theileriosis was confirmed by microscopic examination of stained blood smears and lymphnode smearsfurther confirmed by PCR assay. Electrocardiography was performed byusing the base apex lead system, and echocardiography was performed byusing the right parasternal view. The incidence of theileriosis was 16.25% by examination of stained blood smears, and 30.42% by PCR examination in 240 buffaloes. Repeatedly noted clinical signs were the absence of rumination, anorexia, loss of milk yield, depressed demeanour, emaciation, hyperthermia, lymphadenopathy, tick infestation, tachycardia, cardiac arrhythmia, and increased intensity of heartbeat. Haematological findings disclosed decreased haemoglobin, packed cell volume, total erythrocyte count, and neutrophils; increased eosinophils and monocytes. Serum biochemical findings revealed decreased albumin, albumin/globulin ratio, glucose, calcium, phosphorous, sodium, potassium, and chloride; increased globulin, aspartate aminotransferase, bilirubin, blood urea nitrogen, creatinine, cholesterol, lactate dehydrogenase, gamma-glutamyl transferase, and creatine kinase myocardial band isoenzymes. Electrocardiography explorations were sinus tachycardia, broad T wave, and sinus arrhythmia. Echocardiography examination showed ventricular wall thickening, cardiac chamber dilatation, valvular defects/valvular regurgitation, and pericarditis/cardiac tamponade. The present research proposes the changes in the electrocardiography and echocardiography findings in buffaloes with theileriosis, which are essential in clinics to identify the secondary complications during theileriosis and formulate therapeutics.

6420 Organokines and Liver Enzymes in Adolescent Girls with Polycystic Ovary Syndrome During Randomized Treatments

Abstract Disclosure: C. Garcia-Beltran: None. M. Peyrou: None. F.E. de Zegher: None. A. López-Bermejo: None. F. Villarroya: None. L. Ibanez: None. Introduction: Polycystic ovary syndrome (PCOS) is often related to metabolic associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function and systemic dysmetabolism and with abnormal circulating levels of signaling molecules, so-called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage which were assessed longitudinally in the aforementioned studies as safety markers. Materials and Methods: Liver enzymes [aspartate aminotransferase (AST), alanine amino transferase (ALT) and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) to those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 yr. As a post-hoc endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI) and meteorin-like protein (METRNL), were assessed by ELISA after 6 months on OC (N=26) or spiomet (N= 28). Auxological, endocrine-metabolic, body composition (by DXA) and abdominal fat partitioning (by MRI) were also evaluated. Healthy age-matched adolescent girls (N=17) served as controls. Results: Circulating ALT and GGT levels raised during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 mo on treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls as compared to controls and spiomet-treated girls; (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels directly correlated with circulating METRNL levels only in OC-treated girls (R=0.449; P=0.036 and R=0.552; P=0.004, respectively). Conclusion: The on-treatment increase in ALT and GGT levels occurring only in OC-treated girls associates with circulating METRNL levels suggesting an enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment. Trial registration numbers: ISRCTN29234515 (https://doi.org/10.1186/ISRCTN29234515) and ISRCTN11062950 (https://doi.org/10.1186/ISRCTN11062950) Presentation: 6/2/2024

6420 Organokines and Liver Enzymes in Adolescent Girls with Polycystic Ovary Syndrome During Randomized Treatments

Abstract Disclosure: C. Garcia-Beltran: None. M. Peyrou: None. F.E. de Zegher: None. A. López-Bermejo: None. F. Villarroya: None. L. Ibanez: None. Introduction: Polycystic ovary syndrome (PCOS) is often related to metabolic associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function and systemic dysmetabolism and with abnormal circulating levels of signaling molecules, so-called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage which were assessed longitudinally in the aforementioned studies as safety markers. Materials and Methods: Liver enzymes [aspartate aminotransferase (AST), alanine amino transferase (ALT) and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) to those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 yr. As a post-hoc endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI) and meteorin-like protein (METRNL), were assessed by ELISA after 6 months on OC (N=26) or spiomet (N= 28). Auxological, endocrine-metabolic, body composition (by DXA) and abdominal fat partitioning (by MRI) were also evaluated. Healthy age-matched adolescent girls (N=17) served as controls. Results: Circulating ALT and GGT levels raised during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 mo on treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls as compared to controls and spiomet-treated girls; (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels directly correlated with circulating METRNL levels only in OC-treated girls (R=0.449; P=0.036 and R=0.552; P=0.004, respectively). Conclusion: The on-treatment increase in ALT and GGT levels occurring only in OC-treated girls associates with circulating METRNL levels suggesting an enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment. Trial registration numbers: ISRCTN29234515 (https://doi.org/10.1186/ISRCTN29234515) and ISRCTN11062950 (https://doi.org/10.1186/ISRCTN11062950) Presentation: 6/2/2024

8450 Accelerometer-based Sedentary Time and Physical Activity with the Risk of Severe Liver Steatosis and Liver Cirrhosis in 2684 Children: A 13-Year Longitudinal and Mediation Study

Abstract Disclosure: A.O. Agbaje: None. Background: Non-alcoholic fatty liver diseases have been associated with physical inactivity in adults. However, long-term evidence on the prospective relationship of accelerometer-measured sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous PA (MVPA) with liver steatosis and fibrosis and changes in liver enzymes in a large paediatric population is scarce. Hypothesis: It was hypothesized that increased ST from childhood through young adulthood would increase the risk of severe liver steatosis and cirrhosis and worsen liver enzymes, whereas engaging in LPA and MVPA would reduce the risk. Methods: From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 2684 children aged 11 years who had at least one follow-up time-point accelerometer-measured ST, LPA, and MVPA over a period of 13 years, and liver indices and enzymes measures at age 24 years clinic visit were included. Liver steatosis and fibrosis were assessed by transient elastography (FibroScan 502 Touch) and categorized as fibrosis stage F0-F4 and steatosis grade (S0-S3) at age 24 years. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were assayed at ages 17 and 24 years. Longitudinal associations were examined using generalized linear mixed-effect models, while mediation analyses were conducted with structural equation models. Results: Among 2684 children (mean [SD] age, 11.75 [0.24] years; 1537 [57.3%] females]), ST increased from 6 hours/day in childhood to 9 hours/day in young adulthood, while LPA decreased from 6 hours/day to 3 hours/day and MVPA was relatively stable at 50 minutes/day. The prevalence of liver cirrhosis [F4, ≥11·7 kPa] and severe liver steatosis [S3, controlled attenuation parameter value ≥280 dB/m] is 0.3 and 10%, respectively. Cumulative 1-minute/day increase in ST from ages 11-24 years was associated with higher odds of liver cirrhosis (odds ratio 1.004 [95% CI 1.002 - 1.005] p&amp;lt;0.001) and severe liver steatosis (1.001 [1.001 - 1.002] p=0.002) at age 24 years. Increased ST from childhood was directly associated with increased ALT, AST, and GGT from ages 17 - 24 years. Cumulative 1-minute/day LPA was associated with lower odds of liver cirrhosis (0.990 [0.990 - 0.991] p&amp;lt;0.001) and severe liver steatosis (0.999 [0.998 - 0.999] p&amp;lt;0.001) at age 24 years, as well as decreased liver enzymes. Cumulative 1-minute/day MVPA was associated with associated with lower odds of severe liver steatosis (0.996 [0.994 - 0.998] p&amp;lt;0.001) but not liver cirrhosis at age 24 years. MVPA effect on lowering liver steatosis was significantly suppressed (64% suppression) by increased fat mass. Conclusions: Increasing LPA, sustaining MVPA, and decreasing ST from childhood may independently attenuate and reverse the risk of severe liver steatosis and cirrhosis by young adulthood. Presentation: 6/1/2024

6976 Early-Onset Paget's Disease- A Unique Presentation In A Young Female With Elevated Alkaline Phosphatase And Low Back Pain

Abstract Disclosure: F. El Sayed: None. Background Paget disease of bone is an age-related disorder characterized by abnormal growth in certain bones, leading to changes in size and shape. Commonly affecting the skull, spine, pelvis, and long bones, it is more prevalent in men, those over 55, with a family history, and of European ancestry. The prevalence of Paget's disease of bone is approximately 2-3% in individuals over 55 in the United States and Europe, with higher rates in those of European descent. Symptoms, such as pain and deformities, may arise from the condition itself or complications like arthritis. While Paget disease can cause visible abnormalities and fractures in affected bones, most individuals remain asymptomatic. Diagnosis often involves blood tests measuring alkaline phosphatase levels, bone scans, and x-rays. Case Presentation We present the case of a 34-year-old woman who sought evaluation due to persistently elevated alkaline phosphatase (ALP) levels in the thousands. The abnormality was discovered during routine blood work conducted during her pregnancy in 2020, and subsequent investigation revealed a chronic elevation for over three years. The patient reported chronic lower back pain but denied other neurological symptoms. Quantification of ALP Bone showed elevated levels at 629, with normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as well as within-range calcium and gamma-glutamyl transferase (GGT). A whole-body bone scan revealed marked radio tracer uptake in the calvarium, raising concerns for Paget's disease. The patient received a one-time infusion of Zoledronic acid (5 mg), leading to a significant decrease in ALP levels to 182 after three months. Subsequent examination by an Ear, Nose, and Throat (ENT) specialist unveiled bilateral extra bone deposition and mild hearing loss in the right ear, adding a unique dimension to the patient's presentation. This case highlights the importance of a comprehensive approach to diagnose and manage Paget's disease, even in younger individuals with atypical symptoms. Discussion and conclusion Paget's disease presenting in young adults with back pain can be a diagnostic challenge due to its atypical occurrence in this age group. Although back pain is a common symptom, the underlying cause might not immediately be linked to Paget's disease, which typically affects older individuals. However, when encountering persistent back pain in young adults, especially when accompanied by elevated alkaline phosphatase levels, clinicians should consider Paget's disease as a potential differential diagnosis. Further investigation, including imaging studies and bone scans, becomes crucial to confirm the presence of Paget's disease and initiate appropriate management strategies to mitigate its impact on the patient's health and quality of life. Presentation: 6/2/2024

Changes in Selected Biochemical Markers of Honey Bees Exposed to Fermented Common Tansy Solution (Tanacetum vulgare L.).

Honey bees use pollen and nectar from flowers to produce food. Because they often forage on crops, they are at risk of being exposed to plant protection products (PPPs), both directly and in stored food. Due to the adverse effects of synthetic PPPs on pollinators, biopesticides may be a viable alternative. Common tansy extract is used as one of the natural substitutes for synthetic pesticides. In our study, the effect of fermented common tansy extract on aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGTP) activity and the concentration of triglycerides (TGs), total protein (TP), total antioxidant status (TAS), and glucose in honey bee workers' hemolymph was assessed. These biochemical markers give valuable information about the immunity, detoxification, and nutrition of a bee's body. Caged bees were given tansy extract added at various concentrations in sugar syrup for 24 h. Then, they were provided with only sugar syrup. After 7 days of the experiment, hemolymph was collected and analyzed. We observed changes in the activity of AST, ALT, GGTP enzymes and TG, TP, and glucose levels, but not all changes were statistically significant. In terms of AST activity, statistically significant differences were found. All groups tested, including the negative control group, showed reduced enzyme activity values compared to the positive control group. In TG concentration, differences were observed between the groups receiving 2% extract and 1% ethanol. Glucose levels differed between the groups receiving 1% extract and 2% extract and between the positive control group and 1% extract. Bee body proper functioning is affected by changes in enzyme activity, especially those responsible for immunity and detoxification, such as AST, ALT, ALP, and GGTP. Despite the short time of bees' exposure to the agent, the results of study show visible effects. Our results provide a basis for further research on the impact of tansy extract on honey bees.

A-093 Assessing Alkaline Phosphatase Reference Intervals Using Gamma-Glutamyl Transferase as a Surrogate for Normal Liver Function

Abstract Background There are limited published studies assessing reference intervals (RIs) for hepatic enzymes, particularly for alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT). In the US, ALP and GGT RIs were established on Roche assays using a European cohort of ≤ 450 patients that may not reflect population variance across practice settings. Further, age- and sex-specific variation in ALP and GGT may warrant tiered RIs, but evidence to justify this approach is limited. We aimed to evaluate the manufacturer’s RIs by comparing them to indirectly estimated RIs (IRIs) from routine clinical data. Methods 217,333 AST, ALT, ALP, and GGT results (Roche c702) performed between 1/1/2019-12/31/2022 on outpatients ≥21 years were extracted from the laboratory information system. The first ALP for each patient was identified, and the earliest AST, ALT, and GGT drawn within 7 days was included. This approach was repeated for GGT. Concordance and correlation were calculated using Weighted Cohen’s Kappa and Spearman’s rank correlation coefficient respectively. {refineR}, an algorithm for calculating IRIs, was applied to patients with “normal” liver function (defined as normal AST, ALT for all IRIs, plus normal GGT for ALP IRIs, and ALP for GGT IRIs). IRIs were estimated for all males, all females, females ≤50, and females &amp;gt;50 years and compared to the method specific manufacturer RI (ALP: 40-129 Units/L for males and 35-104 Units/L for females; GGT: 8-61 Units/L for males and 5-36 Units/L for females). Results Of the 71,783 outpatients, 54.9% were female, 74% self-identified as white and 19% as black. The median age was 58 (IQR: 43-68 years), the median ALP concentration was 77 (62-97 Units/L), and the median GGT concentration was 28 (17-57 Units/L). A moderate agreement between ALP and GGT was observed (Kappa = 0.48, 95% confidence interval: 0.46-0.51). A positive correlation between ALP and GGT was observed r = 0.51 (p&amp;lt;0.0001). For ALP, no significant differences were observed between the lower limit of the IRIs and the current RI. The upper limit of estimated IRIs was 132 [95% confidence interval: 117-147 Units/L] for patients with normal AST/ALT/GGT (n = 1596). For males, the sex-specific upper limit was 120 [101-140 Units/L] and for females, was 123 [110-136 Units/L]. Age stratified upper limits for females were 120 [101-140 Units/L], and 109 [97-121 Units/L] for ≤50 and &amp;gt;50 years, respectively. For GGT, no significant differences were observed for the lower limits. The upper limit for all patients with normal AST/ALT/ALP (n = 2,446) was 62 [55-70 Units/L]. For males, all females, females ≤50 and &amp;gt;50 years was 58 [46-69 Units/L], 40 [39-51 Units/L], 31 [23-39 Units/L], and 56 [41-71 Units/L]. Conclusions For the majority of patient subsets, the manufacturer RI agreed well with the IRIs. However, significant differences in IRIs were observed for the upper limit of ALP IRIs of all females with normal hepatobilliary function and in GGT for all females and females &amp;gt;50 years. Further investigation of the impact of preselecting patient populations on IRI estimation and a direct RI study on select patient subsets is worth investigation.

Impact of Comorbid Polycystic Ovary Syndrome on Clinical and Laboratory Parameters in Female Adolescents with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Cross-Sectional Study

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) share several pathophysiological mechanisms. While the prevalence of MASLD has been extensively studied in PCOS populations, the occurrence of PCOS among female adolescents with transient elastography (TE)-confirmed MASLD in pediatric hepatology settings remains poorly characterized. This cross-sectional study aims to address this knowledge gap and elucidate potential clinical and biochemical differences between female adolescents with MASLD and comorbid PCOS compared to those without PCOS. Methods: The study cohort included 45 female adolescents with TE-diagnosed MASLD. Comparative analyses of clinical and laboratory parameters were performed between those with (n = 19) and those without (n = 26) comorbid PCOS, diagnosed according to the Rotterdam criteria. Results: Adolescents with MASLD and comorbid PCOS exhibited significantly higher weight, lower height, and increased waist circumference compared to those without PCOS. Additionally, the prevalence of acanthosis nigricans was significantly higher in the PCOS group (68.4% versus 34.6%, p = 0.025). Regarding laboratory parameters, serum phosphorus levels and liver enzymes—including aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase—were significantly lower in adolescents with comorbid PCOS. However, no significant differences were observed in lipid profiles, glucose metabolism, or novel non-invasive biomarkers of MASLD. Conclusions: This study reveals distinct clinical and biochemical profiles in female adolescents with MASLD and comorbid PCOS compared to those without PCOS. These findings have the potential to inform and refine future screening protocols and diagnostic algorithms for these interrelated conditions, specifically tailored to pediatric hepatology settings.

Capecitabine enhances sensitivity to oxaliplatin in advanced gastric cancer and the effects on patients' FOXP1 and GGT levels

ObjectiveTo investigate the effect of capecitabine on the sensitivity of oxaliplatin and on the level of transcription factor forkhead box P1 (FOXP1) and gamma-glutamyl transpeptidase (GGT) in patients with intermediate and advanced gastric cancer. MethodsA total of 152 patients with intermediate and advanced gastric cancer diagnosed and treated in our hospital from April 2018 to May 2019 was selected as the research objects, and their clinical data were retrospectively analyzed. According to the different treatment methods, they were divided into the study group and the control group, with 76 cases in each group. The patients in the control group received with oxaliplatin, while the patients in the study group received with capecitabine on the basis of the control group. The therapeutic effect was evaluated according to the therapeutic effect evaluation criteria of solid tumors. The FOXP1 expression level in gastric cancer tissues was detected using immunohistochemistry. Serum levels of GGT were measured by chemiluminescence. The prognostic factors were analyzed by COX regression model, and the Kaplan-Meier survival curve was used to analyze the relationship between the influencing factors and the survival of gastric cancer. ResultsThe effective rate of capecitabine combined with oxaliplatin and oxaliplatin alone in the treatment of patients with intermediate and advanced gastric cancer were 94.74% and 76.32% respectively. Capecitabine enhanced the sensitivity of intermediate and advanced gastric cancer to oxaliplatin (P<0.05). Compared with adjacent normal tissues, the expression level of FOXP1 in gastric cancer tissues was lower (P<0.05). Before treatment, the expression of FOXP1 was low, and no significant difference was observed in the GGT level between the two groups (P>0.05). After treatment, the low expression rate of FOXP1 and serum GGT level were both significantly decreased, and those in the study group were lower than those in the control group (P<0.05). There was no difference in the incidence of adverse reactions between the two groups (P>0.05). The 1-year survival rates of the study group and the control group were 90.79% and 78.95%, while the 3-year survival rates of the study group and the control group were 75.00% and 51.32%, respectively. Both the 1-year and 3-year survival rate of the study group was higher than that in the control group (P<0.05). The 1-year survival rate of 152 patients with gastric cancer was 84.87% (129/152) and the 3-year survival rate was 63.17% (96/152). Age, tumor diameter, tumor-node-metastasis (TNM) stage, lymph node metastasis, chemotherapy regimen and the expression of FOXP1 and GGT had significant effects on the survival rate (P<0.05). Gastric cancer patients with age < 60 years, TNM stage of Ⅰ ∼ Ⅱ, lymph node metastasis N0 ∼ N1, high expression of FOXP1, GGT < 387.2, and combined with drug chemotherapy had higher survival rate. ConclusionCapecitabine effectively enhanced the sensitivity of intermediate and advanced gastric cancer to oxaliplatin, improved the therapeutic effect, reduced the proportion of patients with low FOXP1 expression rate and serum GGT level, decreased the recurrence rate and ameliorated the prognosis of patients.This is a retrospective study, all data were analyzed retrospectively. This research was approved by the Ethics Review Committees of Fuwai Central China Cardiovascular Hospital (approval number: 2023-EC-015).

Study on the correlation between fatty liver index and the outcome of high normal blood pressure

Objective: To analyze the correlation between fatty liver index (FLI) and the outcomes of individuals with high normal blood pressure. Methods: In this retrospective cohort study, data from the follow-up population of the Beijing branch of the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal (REACTION) study conducted from December 2011 to August 2012 were selected. Obtain indicators such as height, weight, waist circumference, fasting blood glucose, 2-h postprandial blood glucose, triglycerides, high-density lipoprotein cholesterol, and glutamyl transpeptidase were measured, and the FLI was calculated. The population with high normal blood pressure was divided into the FLI<30 group (1 822 cases); 30≤FLI<60 group (1 026 cases); and FLI≥60 group (473 cases) based on FLI levels. The blood pressure outcome data from the follow-up survey of this population from April 2015 to September 2015 were collected. Single factor analysis of variance was used for intergroup comparison, and logistic regression was used to analyze the correlation between FLI and the outcome of high normal blood pressure in the population. Results: The FLI was an independent influencing factor for their conversion to normal blood pressure (all P<0.01). Among all observed populations, the likelihood of conversion to normal blood pressure in the 30≤FLI<60 group and FLI≥60 group was 0.63 (95%CI 0.51-0.78) and 0.61 (95%CI 0.45-0.82) of the FLI<30 group, respectively. In the population of 40≤age<60 years, this likelihood was 0.60 (95%CI 0.47-0.76) and 0.57 (95%CI 0.41-0.79), respectively. FLI is not an independent influencing factor for the conversion to normal blood pressure in individuals aged over 60 years (P=0.161). FLI is an independent risk factor for hypertension (all P<0.05). Among all observed populations and population of 40≤age<60 years and age>60 years, the risk of hypertension in the 30≤FLI<60 group and FLI≥60 group was 1.49 times (95%CI 1.23-1.80) and 1.54 times (95%CI 1.19-1.98); 1.41 times (95%CI 1.13-1.75) and 1.38 times (95%CI 1.04-1.83); and 1.75 times (95%CI 1.22-2.53) and 2.10 times (95%CI 1.24-3.58) of the FLI<30 group, respectively. Conclusions: There is a correlation between FLI levels and future outcomes of individuals with normal high blood pressure. Although people with higher FLI are more likely to develop hypertension, those with higher FLI are also less likely to develop normal blood pressure in the 40≤age<60-year group.