Gamma-glutamyl Transferase Values Research Articles

P0591 Janus Kinase Inhibitors Improve Liver Biochemistry in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease: an ECCO CONFER Study.

Abstract Background JAK inhibitors (JAKi) can induce and maintain remission in inflammatory bowel disease (IBD). Around 5% of IBD patients develop primary sclerosing cholangitis (PSC). Given the potential involvement of JAK/STAT signaling in PSC pathogenesis, JAKi may have a role in modulating IBD-related PSC. We aim to explore the course of PSC in IBD-PSC patients on JAKi for IBD. Methods Following a call-for-cases via ECCO CONFER (Round 10), we retrospectively collected baseline and outcome data for both PSC and IBD, before and after JAKi treatment, including laboratory tests, imaging and endoscopic findings, histopathology and adverse effects. The data were analyzed both descriptively and comparatively. A p-value of less than 0.05 was considered statistically significant. Results We collected data from 58 patients (53 ulcerative colitis), with a median of disease duration of 5.5 (IQR 2-9) years (Table 1). The median age at PSC diagnosis was 26 (18.25-40.5) years. Each patient had been treated with a median of 2.5 different types of drugs before starting JAKi; 57% received tofacitinib, 26% upadacitinib, 17% filgotinib. At the time of data analysis, the median time of JAKi exposure was 32 (15.75-69) weeks and we will refer to that median time of exposure when analysing each data related to JAKi exposure. At baseline, alkaline phosphatase (ALP) was elevated in 71% of patients (median, 292 U/L, 185-471). After JAKi exposure, ALP dropped to a median of 203.5 U/L (138.7-394.5), p=0.0004. Among this specific group, 30% of subjects reached normal ALP values. Gamma-glutamyl transferase (GGT) was elevated in 80% of patients (350 U/L, 164-552) and dropped to a median value of 127 U/L (95-270), p=0.0055; 13% of this specific group reached normal values of GGT after JAKi exposure. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were high in 58% and 50% of patients, respectively; following JAKi exposure, the median value of both went down significantly. After a median time of 32 weeks of JAKi treatment, 39,6% of patients had to change therapy: 23% due to primary non-response, 62% due to lack of response, 15% underwent colectomy. Patients who had to change therapy were divided into: switch group, treated with additional 40 (36-46) weeks with a different JAKi; swap group, swapped to biologic for additional 27 (24-40) weeks. Better control of liver biomarkers was observed in the switch group (Figure 1). Conclusion Treatment with JAKi can positively impact liver inflammation in terms of cholestasis and cytolysis indexes in patients with PSC and concomitant IBD. References Schregel I, Ramos GP, Ioannou S, Culver E, Färkkilä M, Schramm C; International PSC Study Group. Evaluation of Tofacitinib in Primary Sclerosing Cholangitis and Associated Colitis: A Multicenter, Retrospective Study. Clin Gastroenterol Hepatol. 2023;21(13):3448-3450.e3. doi: 10.1016/j.cgh.2023.01.014. Khrom M, Long M, Dube S, Robbins L, Botwin GJ, Yang S, Mengesha E, Li D, Naito T, Bonthala NN, Ha C, Melmed G, Rabizadeh S, Syal G, Vasiliauskas E, Ziring D, Brant SR, Cho J, Duerr RH, Rioux J, Schumm P, Silverberg M, Ananthakrishnan AN, Faubion WA, Jabri B, Lira SA, Newberry RD, Sandler RS, Xavier RJ, Kugathasan S, Hercules D, Targan SR, RB Sartor, Haritunians T, McGovern DPB. Comprehensive association analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease. Gastroenterology. 2024;167(2):315-332. doi: 10.1053/j.gastro.2024.02.026. Dold L, Kalthoff S, Frank L, Zhou T, Esser P, Lutz P, Strassburg CP, Spengler U, Langhans B. STAT Activation in Regulatory CD4 (+) T Cells of Patients with Primary Sclerosis Cholangitis. Immune Inflamm Dis. 2024;12(4):e1248. doi: 10.1002/iid3.1248.

Enzymic Activity, Metabolites, and Hematological Responses Changes of Clinical Healthy High-Risk Beef Calves During Their First 56-Days from Arrival.

The objective of this study was to evaluate the changes in enzymic activity, metabolites, and hematological responses during the first 56-d of arrival of newly received calves, which were qualified at reception as high-risk but diagnosed as clinically healthy. A total of 320 blood samples were taken from 64 crossbred bull calves (average initial body weight = 148.3 ± 1.3 kg) at different times from arrival (d 0, 14, 28, 42, and 56 of received). Calves included in the study were received in June (n = 20), November (n = 24), and April (n = 20); thus, experimental treatments were arranged in a generalized complete block design (three blocks = month of arrival). The following parameters were determined: total white blood cells (WBC): lymphocytes (LYM), lymphocytes % (LYM%), monocytes (MON), monocytes % (MON%), granulocytes (GRA), granulocytes % (GRA%), platelets (PLT), and mean platelet volume (MPV); red blood cells (RBC): red blood cell distribution width test % (RDW%), hematocrit (HCT), and mean corpuscular volume (MCV); hemoglobin (HGB): mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). The enzymatic activity and metabolites analyzed were alkaline phosphatase (ALP), gamma glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein (TP), albumin (ALB), globulin (GLO), ALB/GLO ratio, blood urea nitrogen (BUN), creatinine (CRE), total bilirubin (TBIL), total cholesterol (TCHO), triglycerides (TG); (4) calcium (Ca), glucose (GLU), sodium (Na+), potassium (K+), and chlorine (Cl-). It was observed that ALP, ALT, TP, ALB, GLO, ALB/GLO ratio, TCHO, TG, Ca, and GLU increased as days from reception increased (linear effect, p ≤ 0.04), whereas CRE and TBIL were reduced (linear effect, p ≤ 0.02). A quadratic response (p ≤ 0.001) was observed to GGT and AST values being maximal on days 1 and 56 after arrival (p ≤ 0.001). Na+, K+, and Cl- concentrations were not affected by prolonged days after arrival. Finally, blood cells of LYM, LYM%, PLT, RBC, HGB, HCT%, MCV, and MCH increased (linear effect, p ≤ 0.001) as the number of days after arrival increased. Whereas MON% was linearly decreased (p ≤ 0.05). It was concluded that even when all parameters were within the range of reference intervals (RIs) determined for healthy cattle, during the period of monitoring, as the days after arrival lengthened, blood serum parameters related to health and immunity increased, and metabolites related to tissue injury decreased. In contrast, plasmatic electrolytes (Na+, K+, and Cl-) were slightly reduced as the day after arrival increased. Apparently, at least 42 d is the minimum period after arrival to permit calves to reach more adequate physiological and metabolic conditions before starting the fattening phase.

Correlation between Length-to-width Ratio of Gallbladder and Gamma-glutamyl Transferase Value in Biliary Atresia

Biliary atresia represents one of the most prevalent etiologies for neonatal cholestasis. Unmanaged biliary atresia can be fatal. Ultrasonography is the primary diagnostic test because it's accurate, cost-effective, and available. Various ultrasound findings can assist in diagnosing biliary atresia; the length-to-width ratio of the gallbladder is a particularly advantageous method, offering a short examination time, objectivity, and ease of use, with an accuracy rate of 78.9%. In cases with unconventional ultrasound findings, gamma-glutamyl transferase is believed to be able to complete the diagnostic process with an accuracy rate of up to 80%. The optimal cut-off value differs between studies, making it challenging to use as a benchmark for biliary atresia detection. In this study, researchers aim to further investigate the relationship between length-to-width ratio and gamma-glutamyl transferase in cases of biliary atresia, compared to the liver biopsy results in these patients and the optimal cut-off. This study employed an observational analytic approach with a retrospective design. The sample population consisted of all patients with neonatal cholestasis who underwent laboratory and ultrasonographic examinations at Dr. Soetomo Academic General Hospital Surabaya between 2019 and 2023. The study population comprised 82 patients. A significant relationship (p-value<0.001) was observed between the length-to-width ratio of the gallbladder and biliary atresia, as well as between gamma-glutamyl transferase and biliary atresia (area under the curve: 0.7–0.8). However, the analysis between the length-to-width ratio of the gallbladder and the value of gamma-glutamyl transferase showed p-value=0.066, which means no significant relationship was observed between the length-to-width ratio and gamma-glutamyl transferase.

Edaravone’s Hepatoprotective Effects Against Oxidative Stress in Valproic acid –induced rat model

In this experimental study, the effect of edaravone (EDA) on liver damage caused by valproic acid (VPA) was investigated. The antioxidant, oxidative stress, and inflammation indicators such as glutathione (GSH), total lipid (TL), sialic acid (SA), aspartate (AST) and alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) were examined. Male Sprague Dawley rats were used in the experiment and randomly divided into 4 groups. The experiment lasted for 7 days. Group I: control group rats; Group II: rats receiving 0.5 g/kg VPA intraperitoneally daily. Group III: rats receiving 30 mg/kg EDA intraperitoneally daily. Group IV: rats receiving 0.5 g/kg VPA and 30 mg/kg EDA intraperitoneally daily (at the same time). On day 8, all animals were sacrificed under anesthesia, and liver tissues were removed. VPA caused the decreases in GSH, CAT, SOD, GPx, GR, and GST values and the increases in AST, ALT, ALP, GGT, sialic acid, and total lipid values. EDA reversed the in all values. These results suggest that EDA administration potentially reduces liver injury in VPA-induced hepatotoxicity.

Evaluation of Oxidative Stress, Thyroid Hormones, Trace Elements and Some Biochemical Markers in Goats Naturally Infected with Theileria ovis.

Theileriosis is a tick-borne disease caused by protozoon species in the Theileria genus of the Theileriidae family. The biochemical changes induced by infection are considered to be an important understanding of the pathophysiology of caprine theileriosis. In this study, it was aimed to determine oxidative stress, thyroid hormones, trace elements, and biochemical parameters in theileriosis infection. A sample of 14 goat was used for this purpose, of which 7 were healthy and 7 were infected with Theileria ovis. Theileria infection was diagnosed from the polymerase chain reaction (PCR). Sera from blood samples was tested for total antioxidant capacity (TAC), total oxidant capacity (TOC), oxidative stress index (OSI), alanine aminotransferase (ALT), aspartate transaminase (AST), gamma glutamyl transferase (GGT), total protein, albumin, triglyceride, cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), urea, blood urea nitrogen (BUN), creatinine, triiodothyronine (T3), thyroxine (T4), copper (Cu), zinc (Zn), cobalt (Co), manganese (Mn), selenium (Se), iron (Fe). TOC, OSI, AST, ALT and GGT values were higher in the patient group than in the healthy group (P < 0.05). On the other hand, there were decreases in TAC, T3, T4, total protein, albumin, creatinine, Cu, Zn, Se, and Co values (P < 0.05). However, there was not found to be a statistical difference between the healthy and patient groups in terms of triglyceride, cholesterol, HDL, LDL, urea, BUN, Mn, and Fe values (P > 0.05). It can be stated that oxidative stress is a complication of caprine theileriosis and it may be accompanied with hypothyroidism and deficits in trace minerals.

Alcohol consumption and liver phenotype of individuals with alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin deficiency is an inherited disorder caused by alpha-1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver-related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium. Reported alcohol consumption was evaluated in two cohorts: (i) the community-based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non-carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate-deficient transferrin (CDT). In both cohorts, no/low alcohol intake was reported by >80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a <30% increased rate of elevated transaminases and ~50% increase in elevated gamma-glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease. Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption.

A New Alternative Nutritional Source Hawthorn Vinegar: How It Interacts with Protein, Glucose and GLP-1.

(1) Background: There is a balance between nutrition, glycemic control, and immune response. Their roles in physiological mechanisms are essential for maintaining life quality. This study aimed to evaluate hawthorn vinegar's metabolic effects, and describe its possible mechanism. We also pointed out several vinegar production methods to clarify the antioxidant features. (2) Methods: In the study, three vinegar techniques were applied to vinegar: traditional production of hawthorn vinegar (N), thermal pasteurization (P), and ultrasound method (U). Thirty-two female adult Wistar albino rats were randomly separated into four groups: Control, N1 (regular vinegar; 1 mL/kg bw), P1 (pasteurized vinegar; 1 mL/kg bw), and U1(ultrasound treated vinegar; 1 mL/kg bw). Vinegar was administered by oral gavage daily for 45 days. Initial and final weights, the percentage changes of body weight gains, and Gamma-Glutamyl Transferase (GGT) values of plasma and liver were measured. The total protein, globulin, and albumin values of plasma, liver, and intestinal tissue were determined. In addition, plasma glucagon-like peptide-1 (GLP-1) and glucose concentrations were evaluated. (3) Results: There was a statistical increase in total intestinal protein value and an increasing tendency in total protein in plasma and liver in group U1 compared to group Control. However, the GGT concentrations in plasma and liver were slightly lower in group U1 than in group Control. In addition, there were significant increases in plasma GLP-1 values in all experimental groups compared to the Control group (p: 0.015; 576.80 ± 56.06, 773.10 ± 28.92, 700.70 ± 17.05 and 735.00 ± 40.70; respectively groups control, N1, P1, and U1). Also, liver GLP-1 concentrations in groups P1 and U1 were higher than in group Control (p: 0.005; 968.00 ± 25.54, 1176 ± 17.54 and 1174.00 ± 44.06, respectively groups control, P1 and U1). On the other hand, significant decreases were found in plasma glucose concentrations in groups N1 and U1 as to the Control group (p: 0.02; Control: 189.90 ± 15.22, N1: 133.10 ± 7.32 and U1: 142.30 ± 4.14). Besides, liver glucose levels were lower in all experimental groups than in group Control statistically (p: 0.010; 53.47 ± 0.97, 37.99 ± 1.46, 44.52 ± 4.05 and 44.57 ± 2.39, respectively groups control, N1, P1, and U1). (4) Conclusions: The findings suggest that hawthorn vinegar can balance normal physiological conditions via intestinal health, protein profiles, and glycemic control. Additionally, ultrasound application of vinegar may improve the ability of hawthorn vinegar, and have positive effects on general health.

Aquatic assessment of the chelating ability of Silica-stabilized magnetite nanocomposite to lead nitrate toxicity with emphasis to their impact on hepatorenal, oxidative stress, genotoxicity, histopathological, and bioaccumulation parameters in Oreochromis niloticus and Clarias gariepinus

BackgroundIn recent years, anthropogenic activities have released heavy metals and polluted the aquatic environment. This study investigated the ability of the silica-stabilized magnetite (Si-M) nanocomposite materials to dispose of lead nitrate (Pb(NO3)2) toxicity in Nile tilapia and African catfish.ResultsPreliminary toxicity tests were conducted and determined the median lethal concentration (LC50) of lead nitrate (Pb(NO3)2) to Nile tilapia and African catfish to be 5 mg/l. The sublethal concentration, equivalent to 1/20 of the 96-hour LC50 Pb(NO3)2, was selected for our experiment. Fish of each species were divided into four duplicated groups. The first group served as the control negative group, while the second group (Pb group) was exposed to 0.25 mg/l Pb(NO3)2 (1/20 of the 96-hour LC50). The third group (Si-MNPs) was exposed to silica-stabilized magnetite nanoparticles at a concentration of 1 mg/l, and the fourth group (Pb + Si-MNPs) was exposed simultaneously to Pb(NO3)2 and Si-MNPs at the same concentrations as the second and third groups. Throughout the experimental period, no mortalities or abnormal clinical observations were recorded in any of the treated groups, except for melanosis and abnormal nervous behavior observed in some fish in the Pb group. After three weeks of sublethal exposure, we analyzed hepatorenal indices, oxidative stress parameters, and genotoxicity. Values of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), urea, and creatinine were significantly higher in the Pb-intoxicated groups compared to the control and Pb + Si-MNPs groups in both fish species. Oxidative stress parameters showed a significant decrease in reduced glutathione (GSH) concentration, along with a significant increase in malondialdehyde (MDA) and protein carbonyl content (PCC) concentrations, as well as DNA fragmentation percentage in the Pb group. However, these values were nearly restored to control levels in the Pb + Si-MNPs groups. High lead accumulation was observed in the liver and gills of the Pb group, with the least accumulation in the muscles of tilapia and catfish in the Pb + Si-MNPs group. Histopathological analysis of tissue samples from Pb-exposed groups of tilapia and catfish revealed brain vacuolation, gill fusion, hyperplasia, and marked hepatocellular and renal necrosis, contrasting with Pb + Si-MNP group, which appeared to have an apparently normal tissue structure.ConclusionsOur results demonstrate that Si-MNPs are safe and effective aqueous additives in reducing the toxic effects of Pb (NO3)2 on fish tissue through the lead-chelating ability of Si-MNPs in water before being absorbed by fish.

Predictors of Choledocholithiasis in Cholecystectomy Patients and Their Cutoff Values and Prediction Model in Korea in Comparison with the 2019 ASGE Guidelines.

: In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) established clinical predictors for choledocholithiasis. Our study was designed to evaluate these predictors within the Korean clinical context, establish cutoff values, and develop a predictive model. : This retrospective study analyzed patients who underwent laparoscopic cholecystectomy. The relationships between choledocholithiasis and predictors including age, blood tests, and imaging findings were assessed through univariate and multivariate logistic regression analyses. We established Korean cutoff values for these predictors and developed a scoring system for choledocholithiasis using a multivariate logistic regression. The performance of this scoring system was then compared with that of the 2019 ASGE guidelines through a receiver operating characteristic curve. : We established Korean cutoff values for age (>70 years), alanine aminotransferase (>26.5 U/L), aspartate aminotransferase (>28.5 U/L), gamma-glutamyl transferase (GGT; >82.5 U/L), alkaline phosphatase (ALP; >77.5 U/L), and total bilirubin (>0.95 mg/dL). In the multivariate analysis, only age >70 years, GGT >77.5 U/L, ALP >77.5 U/L, and common bile duct dilatation remained significant. We then developed a new Korean risk stratification model from the multivariate analysis, with an area under the curve of 0.777 (95% confidence interval, 0.75 to 0.81). Our model was stratified into the low-risk, intermediate-risk, and high-risk groups with the scores being <1.0, 1.0-5.5, and >5.5, respectively. : Predictors of choledocholithiasis in cholecystectomy patients and their cutoff values in Korean should be adjusted and further studies are needed to develop appropriate guidelines.

HIGHER FATTY LIVER INDEX VALUES AT SIMILAR BLOOD PRESSURE CLASSIFICATION INDICATE HIGH INSULIN RESISTANCE AND POTENTIAL INFLAMMATION

Objective: The relationship between fatty liver, which is visceral fat accumulation, and insulin resistance and inflammation as seen in hypertension classification is not clear. The Fatty Liver Index (FLI) is an established score for metabolic dysfunction-associated fatty liver disease (MASLD), which is associated with a risk of diabetes and cardiovascular disease. FLI is derived from a formula based on body mass index, waist circumference, and triglyceride and gamma-glutamyltransferase values. Design and method: A cross-sectional study enrolling consecutive individuals was conducted at a health checkup center in Japan from January 2022 to November 2022. A total of 3553 men (mean Age 50.6), excluding those with diabetes mellitus and those undergoing treatment for inflammatory diseases, were included in the study, and divided according to the Classification of hypertension in the ESH guideline. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and C-reactive protein (CRP) levels were divided into two groups by FLI (&lt;26 (group L) and &gt; or = 26 (group H)) and compared by Mann-Whitney U test. The cutoff value for fatty liver by FLI was determined by prior abdominal ultrasonography, and was set at 26(sensitivity 0.82, specificity 0.72). Results: Results of single regression analysis with FLI showed significant correlations in systolic blood pressure(r=0.31, p &lt; 0.0001), diastolic blood pressure(r=0.36, p &lt; 0.0001), HOMA-IR(r=0.36, p &lt; 0.0001), and CRP(r=0.08, p &lt; 0.0001). Optimal blood pressure(n=1783, mean FLI; 23.1, mean HOMA-IR; 1.28, mean CRP; 0.098mg/dL), Normal blood pressure(n=807, 33.9, 1.61, 0.14), High-normal blood pressure(n=535, 37.8, 1.90, 0.12), Grade 1 hypertension(n=124, 44.8, 2.0, 0.14), Grade 2 hypertension(n=53, 49.0, 1.71, 0.09), Grade 3 hypertension(n=18, 54.6, 2.89, 0.22), Isolated systolic hypertension(n=118, 36.2, 1.59, 0.09), Isolated diastolic hypertension(n=115, 44.1, 1.94, 0.12). HOMA-IR and CRP of H group were significantly higher than L group (all p &lt; 0.001). Conclusions: Higher FLI values at similar blood pressure levels may indicate high insulin resistance and potential inflammation, suggesting the need for strict management.

Influence of Heat Stress on Body Surface Temperature and Blood Metabolic, Endocrine, and Inflammatory Parameters and Their Correlation in Cows.

This study aimed to determine whether heat stress affected the values and correlations of metabolic, endocrinological, and inflammatory parameters as well as the rectal and body surface temperature of cows in the early and middle stages of lactation. This experiment was conducted in May (thermoneutral period), June (mild heat stress), and July (moderate to severe heat stress). In each period we included 15 cows in early lactation and 15 in mid-lactation. The increase in rectal and body surface temperatures (°C) in moderate to severe heat stress compared to the thermoneutral period in different regions was significant (p < 0.01) and the results are presented as mean and [95%CI]: rectal + 0.9 [0.81-1.02], eye + 6 [5.74-6.25], ear + 13 [11.9-14.0], nose + 3.5 [3.22-3.71], forehead + 6.6 [6.43-6.75], whole head + 7.5 [7.36-7.68], abdomen + 8.5 [8.25-8.77], udder + 7.5 [7.38-7.65], front limb + 6 [5.89-6.12], hind limb + 3.6 [3.46-3.72], and whole body + 9 [8.80-9.21]. During heat stress (in both mild and moderate to severe stress compared to a thermoneutral period), an increase in the values of extracellular heat shock protein 70 (eHsp70), tumor necrosis factor α (TNFα), cortisol (CORT), insulin (INS), revised quantitative insulin sensitivity check index (RQUICKI), urea, creatinine, total bilirubin, aspartate transpaminase (AST), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and creatin kinase (CK) occurred, as well as a decrease in the values of triiodothyronine (T3), thyroxine (T4), non-esterified fatty acids (NEFA), glucose (GLU), β-Hydroxybutyrate (BHB), calcium, phosphorus, total protein (TPROT), albumin (ALB), triglycerides (TGCs), and cholesterol (CHOL). In cows in early lactation compared to cows in mid-lactation, there was a significantly larger increase (p < 0.01) in the values of eHsp70, TNFα, GLU, RQUICKI, and GGT, while the INS increase was smaller during the three experimental periods. The decrease in the values of Ca, CHOL, and TGC was more pronounced in cows in early lactation compared to cows in mid-lactation during the three experimental periods. Rectal temperature was related to eHsp70 (r = 0.38, p < 0.001) and TNFα (r = 0.36, p < 0.01) and showed non-significant poor correlations with other blood parameters. Blood parameters correlate with body surface temperature, with the following most common results: eHsp70 and TNFα showed a moderately to strongly significant positive correlation (r = 0.79-0.96, p < 0.001); CORT, INS, and Creat showed fairly to moderately significant positive correlations; T3, T4, NEFA and GLU showed fairly to moderately significant negative correlations (r = 0.3-0.79; p < 0.01); RQUICKI, urea, AST, and GGT showed fairly and significantly positive correlations; and TGC, CHOL, TPROT, and ALB showed fairly and significantly negative correlations (r = 0.3-0.59; p < 0.01). Measuring the surface temperature of the whole body or head can be a useful tool in evaluating the metabolic response of cows because it has demonstrated an association with inflammation (TNFα, eHsp70), endocrine response (CORT, T3, T4), the increased use of glucose and decreased use of lipids for energy purposes (INS, NEFA, GLU, and RQUICKI), and protein catabolism (ALB, TPROT, urea, Creat), which underlies thermolysis and thermogenesis in cows under heat stress. In future research, it is necessary to examine the causality between body surface area and metabolic parameters.

Biochemical and Hormone Markers in Firefighters: Effects of "Search, Rescue, and Survival Training" and Its Recovery.

Ponce, T, Mainenti, MRM, de Barros, T, Cahuê, FLC, Fernanda, C, Piazera, BKL, Salerno, VP, and Vaisman, M. Biochemical and hormone markers in firefighters: effects of "search, rescue, and survival training" and its recovery. J Strength Cond Res 38(4): e189-e201, 2024-This study aimed to evaluate the hormonal and biochemical responses in military firefighter cadets to a search, rescue, and survival training (SRST) course. Forty-three male volunteers participated in the SRST over 15 days consisting of intense physical effort, sleep deprivation, and a survival period with food deprivation. At 3 timepoints (baseline, SRST, and 1 week rec), subjects submitted to blood collections, body composition examinations, physical performance evaluations, and cognitive function tests. After the SRST, lower values were registered for testosterone (764.0; 565.1-895.0 to 180.6; 133.6-253.5 ng·dl -1 ) and insulin-like growth factor-1 (IGF-1) (217; 180-238 to 116; 102-143 ng·ml -1 ). Increases were observed for cortisol (9.7; 8.2-11.7 to 18.3; 16.5-21,2 μg·dl -1 ), growth hormone (GH) (0.11; 0.06-0.20 to 2.17; 1.4-3.4 ng·ml -1 ), CP, GSSG, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase as well as the antioxidant response of superoxide dismutase and glutathione peroxidase. The values of gamma-glutamyl transferase were reduced. After 1 week of recovery, levels of GH, creatine kinase, GSH, and GSSG returned to baseline values ( p < 0.05). Vertical jump performance presented a regular positive correlation with testosterone (rho = 0.56 and p < 0.0001) and a strong negative correlation with cortisol (rho = -0.61 and p < 0.0001). Body fat showed a regular and positive correlation with both testosterone and IGF-1. We conclude that participation in the SRST caused significant hormonal and biochemical changes in individuals that correlated with a loss in physical performance. Importantly, the results suggest the need for longer recovery times before a return to normal military duties.

Gamma-Glutamyl Transferase as a prognostic risk factor in complex coronary disease: a serendipitous (re)discovery of machine learning in the SYNTAXES?

Abstract Background/Introduction Over the last decade, epidemiology and pathology studies have suggested that gamma-glutamyl transferase (GGT) has an independent role in the pathogenesis and clinical evolution of cardiovascular diseases associated with atherosclerosis. Recently, machine learning (ML) algorithms have identified pre-procedural GGT as a significant predictor of long-term mortality after coronary revascularization in the SYNTAX trial. Purpose The aim of this study is to investigate the impact of pre-procedural GGT on 10-year all-cause mortality in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) following revascularization. Methods The SYNTAX trial was a randomized trial comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in 1,800 patients with complex CAD. The present report is a post-hoc sub-analysis of the SYNTAXES study, an investigator-driven extended 10-year follow-up of the SYNTAX trial. Before revascularization, blood samples were taken for GGT as well as other biological markers and analyzed by an independent central chemistry laboratory. The primary endpoint was all-cause mortality at 10-years. The changes in hazard for all-cause mortality in GGT over time were modelled using restricted cubic spline functions in a Cox regression model adjusted by age and sex. Subsequently, we compared survival in four groups defined by gender specific GGT thresholds of &amp;lt;32 IU and ≥32 IU for females and &amp;lt;64 IU and ≥64 IU for males, in accordance with prior studies. Results Out of 1,800 patients enrolled in the SYNTAX study, 167 (9.3%) did not have a GGT available at baseline and 1,633 (90.7%) patients were included in the present study. The mean values of GGT for males and females were 43.5±48.5 and 36.4±46.1 U/L, respectively. In the overall population a 10 U/L increase in GGT was significantly associated with 10-year all-cause death (adjusted hazard ratio [HR] 95% confidence interval [CI]: 1.03 [1.02–1.04], p &amp;lt;0.001, Figure A). For Kaplan–Meier analysis, patients were stratified into four groups according to previously reported sex related GGT thresholds. Ten-year mortality was numerically higher in males (adjusted HR 1.31, 95% CI: 0.90–1.91), and significantly higher in females (adjusted HR 1.88, 95% CI: 1.16–3.05) among patients with higher versus lower GGT (Figure B). Furthermore, GGT was significantly associated with CRP, a surrogate-marker of inflammation, as well as established cardiovascular risk biomarkers such as TG, total cholesterol, and glucose. Conclusions Preprocedural GGT is an independent predictor of 10-year mortality following coronary revascularization in patients with 3VD and/or LMCAD. This long-term association has been identified using ML algorithms and should be corroborated using data from large biobanks.Figure AFigure B

Prevalence of alcohol dependence syndrome in the patients of acute pancreatitis: A cross-sectional study.

Acute pancreatitis (AP) is the main reason for mortality and morbidity. Numerous studies have shown a link between chronic alcohol usage and AP. However, there are few studies on the percentage of patients developing AP as a result of dependent patterns of drinking and associated risk factors. This study aimed to study the prevalence and impact of risk factors of alcohol dependence syndrome with AP patients hospitalized in tertiary care facilities. This is a cross-sectional observational study. Sociodemographic and clinical data were taken from patients with AP after consent. Eighty-five patients with AP who met the inclusion criteria were involved after each participant had clinical evaluation using the modified Marshall score, the Alcohol Use Disorder Identification Test, and the Severity of Alcohol Dependence Questionnaire (SAD-Q). The outcomes were tabulated and analyzed using Statistical Package for the Social Sciences (SPSS) software. 38.8% of patients with AP were found to have features of alcohol dependence syndrome. Higher values of mean corpuscular volume (MCV), serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), Gamma-glutamyl transferase (GGT), and uric acid were associated with a greater propensity to have AP. The severity of alcohol dependence syndrome and AP was not associated. AP is potentially a fatal disease. In this study, 38.8% of AP patients had alcohol dependence syndrome. There was no statistical association between the severity of AP and alcohol dependence syndrome, though high values of MCV, SGOT, SGPT, and GGT were at greater risk of developing AP. As a result, alcohol dependence syndrome should be examined in all individuals with AP.

B-088 Estimation of Antibodies to Hbsag and Liver Function Markers From a Large Laboratory Database in São Paulo, Brazil

Abstract Background The Hepatitis B virus (HBV) infection can lead to chronic hepatitis B and severe hepatic disease. The Gamma Glutamyl Transferase (GGT), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) tests are commonly used to assess liver function. Despite having an effective vaccine schedule, many people in Brazil are still susceptible to HBV. Vaccines use the surface protein (AgHBs) of the virus to induce immunity, and patients with antibody levels above 10 mUL/mL to this protein are considered to have vaccine-induced immunity. The study aims to analyze the pattern of hepatitis B markers and liver function in HBV-positive populations. Methods A retrospective analysis from 2020 to 2022 was conducted from a large laboratory database in São Paulo, Brazil selecting all individuals from whom the following serological diagnostic markers for Hepatitis B were requested: HBsAg, total Anti-HBc, IgM Anti-HBc, and Anti-HBs. HBV groups were classified based upon results for the following serological diagnostic markers: HBsAg, total Anti-HBc, IgM Anti-HBc, and Anti-HBs. The HBV susceptible group was identified as negative for all markers, the naturally immune group with Anti-HBc and Anti-HBs markers, and the vaccinated group with Anti-HBs only. Liver function was evaluated in two conditions: naturally immune and vaccinated, using liver cell injury markers: GGT, AST, and ALT. The Mann-Whitney U and Kruskal-Wallis tests were used for statistical analysis with P &amp;lt; 0.05 considered significant. Results Results from a total of 57 311 (32%) men and 121 404 (68%) women were evaluated. The study observed a lower frequency of individuals in the male vaccinated group (36%) compared to the susceptible group (56%). Conversely, the female group showed a higher frequency of individuals immunized by vaccination (51%) in relation to the susceptible group (45%). The rate of individuals exposed to natural infection was higher in the male group (9%) compared to the female group (4%). Regarding Anti-Hbs antibody levels, higher levels were observed in the population with natural infection markers compared to those immunized by HBV vaccination (527.5 ± 4.0 SEM vs 332.3 ± 1.1 mUI/mL, P &amp;lt; 0.001). Analyzing the age ranges with the greatest susceptibility (31–40 and 41–50 years), a gradual decrease in antibodies was observed over the years when compared: Naturally, P = 0.03, and immunized, P &amp;lt; 0.001). Indicator exams of liver function in both conditions showed average GGT levels above the reference value for the naturally infected groups: female 62.4 ± 5.34 SEM U/L; male 86.7 ± 5.4 SEM U/L, P &amp;lt; 0.001. No significant values of ALT and AST activity levels were seen. Conclusion The study results showed that this specific male population was more susceptible to HBV infection, while the female population has higher concentrations of Anti-HBs antibodies. Individuals who had a natural Hepatitis B infection exhibit GGT values above the standard.

Dose Volume and Liver Function Test Relationship following Radiotheraphy for Right Breast Cancer: A Multicenter Study.

The liver is a critical organ at risk during right breast radiotherapy (RT). Liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) serve as biochemical markers for hepatobiliary damage. In this multicenter cross-sectional study, the effects of liver dose-volume on changes in LFTs pre- and post-RT in patients treated for right breast cancer were evaluated. Between January 2019 and November 2022, data from 100 patients who underwent adjuvant right breast RT across three centers were retrospectively assessed. Target volumes and normal structures were contoured per the RTOG atlas. Patients were treated with a total dose of 50 Gy in 25 fractions to the CTV, followed by a boost to the tumor bed where indicated. The percentage change in LFT values in the first two weeks post-RT was calculated. Statistics were analyzed with SPSS version 22 software, with significance set at p < 0.05. Statistical correlation between liver doses (in cGy) and the volume receiving specific doses (Vx in cc) on the change in LFTs were analyzed using Kolmogorov-Smirnov, Mann-Whitney U test. The median age among the 100 patients was 56 (range: 29-79). Breast-conserving surgery was performed on 75% of the patients. The most common T and N stages were T1 (53%) and N0 (53%), respectively. None of the patients had distant metastasis or simultaneous systemic treatment with RT. A total of 67% of the treatments utilized the IMRT technique and 33% VMAT. The median CTV volume was 802 cc (range: 214-2724 cc). A median boost dose of 10 Gy (range: 10-16 Gy) was applied to 28% of the patients with electrons and 51% with IMRT/VMAT. The median liver volume was 1423 cc (range: 825-2312 cc). Statistical analyses were conducted on a subset of 57 patients for whom all three LFT values were available both pre- and post-RT. In this group, the median values for AST, ALT, and GGT increased up to 15% post-RT compared to pre-RT, and a median liver Dmean below 208 cGy was found significant. While many factors can influence LFT values, during RT planning, attention to liver doses and subsequent regular LFT checks are crucial. Due to factors such as anatomical positioning, planning technique, and breast posture, the liver can receive varying doses during right breast irradiation. Protecting patients from liver toxicity secondary to RT is valuable, especially in breast cancer patients with a long-life expectancy. Our study found that, even in the absence of any systemic treatment or risk factors, there was an average increase of nearly 15% in enzymes, indicating acute liver damage post-RT compared with pre-RT. Attention to liver doses during RT planning and regular follow-up with LFTs is essential.

The Role of Donor Gamma-Glutamyl Transferase as a Risk Factor for Early Graft Function after Liver Transplantation.

Growing interest has been recently reported in the potential detrimental role of donor gamma-glutamyl transferase (GGT) peak at the time of organ procurement regarding the risk of poor outcomes after liver transplantation (LT). However, the literature on this topic is scarce and controversial data exist on the mechanisms justifying such a correlation. This study aims to demonstrate the adverse effect of donor GGT in a large European LT cohort regarding 90-day post-transplant graft loss. This is a retrospective international study investigating 1335 adult patients receiving a first LT from January 2004 to September 2018 in four collaborative European centers. Two different multivariable logistic regression models were constructed to evaluate the risk factors for 90-day post-transplant graft loss, introducing donor GGT as a continuous or dichotomous variable. In both models, donor GGT showed an independent role as a predictor of graft loss. In detail, the log-transformed continuous donor GGT value showed an odds ratio of 1.46 (95% CI = 1.03-2.07; p = 0.03). When the donor GGT peak value was dichotomized using a cut-off of 160 IU/L, the odds ratio was 1.90 (95% CI = 1.20-3.02; p = 0.006). When the graft-loss rates were investigated, significantly higher rates were reported in LT cases with donor GGT ≥160 IU/L. In detail, 90-day graft-loss rates were 23.2% vs. 13.9% in patients with high vs. low donor GGT, respectively (log-rank p = 0.004). Donor GGT was also added to scores conventionally used to predict outcomes (i.e., MELD, D-MELD, DRI, and BAR scores). In all cases, when the score was combined with the donor GGT, an improvement in the model accuracy was observed. Donor GGT could represent a valuable marker for evaluating graft quality at transplantation. Donor GGT should be implemented in scores aimed at predicting post-transplant clinical outcomes. The exact mechanisms correlating GGT and poor LT outcomes should be better clarified and need prospective studies focused on this topic.

Fungal plasma biomarkers in patients admitted for inpatient treatment of alcohol use disorder.

Fungal plasma biomarkers have not been studied in patients with unhealthy alcohol use and no apparent end-stage liver disease. We examined the prevalence of fungal plasma biomarkers, assessed by the presence of anti-Saccharomyces cerevisiae antibodies (ASCA; IgA and IgM), and its disease correlates in patients with alcohol use disorder (AUD). We performed logistic regression analyses to detect the association between clinical and laboratory characteristics and the presence of fungal plasma biomarkers. We included 395 patients (75.9% male, median age of 49 years, and median body mass index of 25.6) who drank a median of 150 g of alcohol daily and had a median duration of AUD of 20 years. ASCA IgA and IgG were present in 34.4% and 14.9%, respectively, and 9.9% had both ASCA IgA and ASCA IgG. The presence of ASCA IgA was associated with male sex (p < 0.01); values of serum aspartate transferase (AST) (p = 0.02), gamma-glutamyl transferase (GGT) (p < 0.01), alkaline phosphatase (ALP) (p < 0.01), and bilirubin in the highest quartile (p < 0.01); Fibrosis-4 Index (FIB-4) values suggestive of advanced liver fibrosis (p < 0.01); and values of the macrophage activation factors sCD163 (p < 0.01) and sCD14 (p < 0.01), the cytokine IL-6 (p = 0.01), and lipopolysaccharide-binding protein in the highest quartile (p < 0.01). The presence of ASCA IgG was associated with omeprazole use (p = 0.04); values of AST (p = 0.04) and GGT (p = 0.04) in the highest quartile; FIB-4 values suggestive of advanced liver fibrosis (p < 0.01); and values of sCD163 (p < 0.01) in the highest quartile. The variables associated with the presence of both ASCA IgA and IgG were male sex (p = 0.04) and values of GGT (p = 0.04) and sCD163 in the highest quartile (p < 0.01). In AUD patients, the presence of fungal biomarkers in plasma was common and associated with FIB-4 values suggestive of advanced liver fibrosis and with markers of liver damage, monocyte activation, and microbial translocation, male gender, and omeprazole use. These findings suggest that the presence of plasma anti-Saccharomyces cerevisiae antibodies could be used as a biomarker for an elevated risk of progressive liver disease in patients with AUD.

Gamma-Glutamyl Transferase as a Diagnostic Marker of Metabolic Syndrome.

Introduction The metabolic syndrome consists of metabolic abnormalities that increase the risk of cardiovascular disease (CVD) and cerebrovascular disease. Metabolic syndrome (MetS) is a growing problem worldwide, and substantial efforts have been made in the last years to identify early, minimally invasive blood-based biomarkers for its diagnosis. This study attempted to assess how serum Gamma-Glutamyl Transferase (GGT) performed as an ideal endogenous substance for the diagnosis of metabolic syndrome and hence estimate cardiovascular risks. Methodology This study has been undertaken to assess the role of GGT as a marker in the diagnosis of metabolic syndrome and toassess the sensitivity and specificity of GGT in the diagnosis of metabolic syndrome. One hundred and eighty subjects were recruited comprising 90 cases of MetS and an equal number of age and gender-matched controls. Patients were recruited into the study group after satisfying the International Diabetes Federation (IDF) criteria for MetS. GGT values were obtained for both groups apart from other parameters. The patients in the study were also evaluated for the presence of cardiovascular diseases and cerebrovascular accidents (CVA). Results Sixty cases have GGT levels above the normal range (55 in males and 38 in females), and none in the control group have GGT levels above normal. This difference is statistically significant (p=0.01). The sensitivity was found to be 67% and 94% for males and females respectively. The specificity was found to be 100% and 98% for males and females respectively. Among the 90 cases, 20 (22.2%) patients developed cardiovascular disease. None in the control group developed cardiovascular disease. This difference is statistically significant (p<0.05). Conclusion Serum GGT appears to be an easily available and fairly good marker for diagnosing patients with metabolic syndrome and is independent of other parameters of metabolic syndrome. It is also a strong predictor of cardiovascular disease. Hence GGT can be considered a potential marker for the evaluation of patients with metabolic syndrome.

Secondary Sclerosing Cholangitis due to Severe COVID-19: An Emerging Disease Entity?

Introduction: Coronavirus disease 2019 (COVID-19) can lead to many extrapulmonary manifestations. In this case series, we report on 7 patients developing secondary sclerosing cholangitis (SSC) after severe COVID-19 with intensive care treatment. Methods: Between March 2020 and November 2021, 544 patient cases with cholangitis treated at a German tertiary care centre were screened for SSC. Patients found to be suffering from SSC were assigned to COVID-19 group if SSC presented after a severe course of COVID-19 and to non-COVID-19 group if not. Peak liver parameters as well as intensive care treatment factors and data generated from liver elastography were compared between both groups. Results: We identified 7 patients who developed SSC after a severe course of COVID-19. In the same period, 4 patients developed SSC due to other causes. Mean values of gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were higher in the COVID-19 group than in the non-COVID-19 group (GGT: 2,689 U/L vs. 1,812 U/L and ALP: 1,445 U/L vs. 1,027 U/L), whereas intensive care treatment factors were comparable in both groups. Only the mean duration of mechanical ventilation was shorter in the COVID-19 group than in the non-COVID-19 group (22.1 days vs. 36.7 days). Liver elastography indicated a fast progression to liver cirrhosis with a mean liver stiffness of 17.3 kilopascals (kPa) in less than 12 weeks in the COVID-19 group. Conclusions: Our data suggest a more severe course of SSC when caused by SARS-CoV-2. Reasons for this are probably multifactorial, including a direct cytopathogenic effect of the virus.