Γ-glutamyl Transpeptidase Research Articles

TORCH serological marker on cholestasis with the occurrence of biliary atresia and its clinical manifestations

Background and objectives. Biliary atresia occurs due to multifactorial etiology, and it was recently suggested that perinatal infection with TORCH, especially Cytomegalovirus (CMV), triggers inflammation of the bile ducts. This study aims to evaluate the TORCH infection on cholestasis with the occurrence of biliary atresia and its clinical manifestations. Materials and methods. A prospective single-center study was performed on 113 cholestatic infants and classified into two groups based on their positivity of immunoglobulin M and G (IgM and IgG). They were tested for CMV, Rubella, and Toxoplasmosis by a Gold Standard Diagnostics ELISA kit in our laboratory. Clinical conditions, laboratory tests (Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), and liver histopathology between the two groups were analyzed with p <0.05 was considered significant. Results. Out of 113 infants of cholestasis, 94.7% (n = 107) were CMV IgG-positive, followed by Rubella IgG-positive (47.8%, n=54). Rubella and toxoplasma IgM antibodies were least commonly found in cholestasis (8% and 7.1%, respectively). CMV IgG-positive status was noted to be older at the onset of jaundice. Infants with Rubella IgG-positive had less incidence of extrahepatic cholestasis (37.7% vs 62.3%) and liver fibrosis (39% vs 61%) (p<0.05). There was no difference in sex, birth weight, gestational age, AST, ALT, GGT, coagulation hemostasis, and abdominal USG abnormality based on torch serological markers (p>0.05). Conclusion: CMV infection mostly occurs in infants with cholestasis, followed by rubella infection. TORCH infection screening may be necessary in all infants with cholestasis.

Association between electroencephalogram-based sleep characteristics and physical health in the general adult population

We examined the associations between electroencephalogram (EEG)-based sleep characteristics and physical health parameters in general adults via a cross-sectional study recruiting 100 volunteers aged 30–59 years. Sleep characteristics were measured at home using a portable multichannel electroencephalography recorder. Using the k-means + + clustering method, according to 10 EEG-based parameters, participants were grouped into better (n = 39), middle (n = 46), and worse (n = 15) sleep groups. Comparing 50 physical health parameters among the groups, we identified four signals of difference (P < 0.05), including systolic (sBP) and diastolic blood pressure (dBP), γ-glutamyl transpeptidase (γ-GTP), and serum creatinine, where sBP reached a Bonferroni-corrected threshold (P < 0.001). The sBP was higher by 7.9 (95% confidence interval 1.9–13.9) and 15.7 (7.3–24.0) mmHg before adjustment and 5.4 (− 0.1–10.9) and 8.7 (1.1–16.3) mmHg after adjustment for age, sex, body mass index, smoking, drinking habits, and 3% oxygen desaturation index in the middle and worse sleep groups, respectively, than in the better group. As another approach, among 500 combinations of EEG-based and physical health parameters, there were 45 signals of correlation, of which 4 (N1% and sBP, dBP, γ-GTP, and triglycerides) reached a Bonferroni-corrected threshold (P < 0.0001). Thus, EEG-based sleep characteristics are associated with several physical health parameters, particularly sBP.

Mildly elevated serum bilirubin and its correlations with lipid levels among male patients undergoing health checkups

BackgroundBilirubin’s ability to lower lipid levels was confirmed by several studies, but those studies mainly focused on total bilirubin (TBil). The present study aimed to elucidate the correlations of the two subtypes of bilirubin with lipid levels.MethodsA total of 1732 male patients undergoing health checkups were categorized into three groups according to the levels of direct bilirubin (DBil) and indirect bilirubin (IBil). The differences in medical characteristics among the three groups were analysed.ResultsSubjects in the elevated DBil group had the lowest serum alanine aminotransferase (ALT), total cholesterol (TC), blood urea nitrogen (BUN), γ-glutamyl transpeptidase (γ-GT), fasting blood glucose (FBG), haemoglobin (HGB), and triglyceride (TG) levels in contrast to the other groups (P < 0.01), while subjects in the elevated IBil group had the highest ALT, γ-GT, BUN, serum creatinine (SCR), HGB, TC, and TG levels among the three groups (P < 0.01). DBil levels exhibited a significant negative correlation with TC (r = -0.777, P < 0.01) and TG (r = -0.397, P < 0.01) levels, while IBil levels exhibited a significant positive correlation with TC (r = 0.790, P < 0.01) and TG (r = 0.302, P < 0.01) levels. The frequencies of abnormal TC, TG, HGB and BUN levels were the lowest in the elevated DBil group, while the levels of these four variables were the highest in the elevated IBil group. Mildly elevated DBil levels were related to lower TG (OR = 0.112, 95% CI = 0.027–0.458) and TC (OR = 0.097, 95% CI = 0.013–0.700), and mildly elevated IBil levels were connected with increased TC (OR = 3.436, 95% CI = 2.398–4.924) and TG (OR = 1.636, 95% CI = 1.163–2.303). DBil was an independent protective factor against increased TC (OR = 0.702, 95% CI = 0.602–0.817, P < 0.01) and TG (OR = 0.632, 95% CI = 0.541–0.739, P < 0.01) levels, and IBil was an independent risk factors for increased TC (OR = 1.251, 95% CI = 1.176–1.331, P < 0.01).ConclusionsDBil was an independent protective factor against high TC and TG levels. IBil was an independent risk factors for elevated TC levels. The prognostic value of IBil levels warrants further attention.

Advances and Perspectives of Responsive Probes for Measuring γ-Glutamyl Transpeptidase.

Gamma-glutamyltransferase (GGT) is a plasma-membrane-bound enzyme that is involved in the γ-glutamyl cycle, like metabolism of glutathione (GSH). This enzyme plays an important role in protecting cells from oxidative stress, thus being tested as a key biomarker for several medical conditions, such as liver injury, carcinogenesis, and tumor progression. For measuring GGT activity, a number of bioanalytical methods have emerged, such as chromatography, colorimetric, electrochemical, and luminescence analyses. Among these approaches, probes that can specifically respond to GGT are contributing significantly to measuring its activity in vitro and in vivo. This review thus aims to highlight the recent advances in the development of responsive probes for GGT measurement and their practical applications. Responsive probes for fluorescence analysis, including "off-on", near-infrared (NIR), two-photon, and ratiometric fluorescence response probes, are initially summarized, followed by discussing the advances in the development of other probes, such as bioluminescence, chemiluminescence, photoacoustic, Raman, magnetic resonance imaging (MRI), and positron emission tomography (PET). The practical applications of the responsive probes in cancer diagnosis and treatment monitoring and GGT inhibitor screening are then highlighted. Based on this information, the advantages, challenges, and prospects of responsive probe technology for GGT measurement are analyzed.

Laparoscopic pancreaticoduodenectomy versus open pancreaticoduodenectomy for carcinoma of the ampulla of Vater in a medium-volume center: a propensity score matching analysis.

To compare the efficacy of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in a medium-volume medical center. Data for patients who underwent OPD or LPD for carcinoma of the ampulla of Vater (VPC) between January 2017 and June 2022 were acquired retrospectively. Propensity score-matching (PSM) analysis was performed to balance the baseline characteristics between the groups. The primary outcome was disease-free survival (DFS). Cox regression analysis was used to explore the independent risk factors for DFS. A total of 124 patients with pathologically diagnosed VPC were included. After 1:1 matching, there were 23 cases each in the OPD and LPD groups. Kaplan-Meier survival analyses showed that the median DFS in the OPD and LPD groups was identical (16.0 months vs 16.0 months, respectively). Multivariate Cox regression analysis showed that low levels of alkaline phosphatase and γ-glutamyl transpeptidase, positive surgical margin, and lymph node enlargement were independent risk factors for DFS. LPD in medium-volume centers with acceptable technical conditions may approach or even achieve the efficacy of LPD in large-volume centers.

Inadvertent perioperative hypothermia and surgical site infections after liver resection

BackgroundIn the overall surgical population, inadvertent perioperative hypothermia has been associated with an increased incidence of surgical site infection (SSI). However, recent clinical trials did not validate this notion. This study aimed to investigate the potential correlation between inadvertent perioperative hypothermia and SSIs following liver resection. MethodsThis retrospective cohort study included all consecutive patients who underwent liver resection between January 2019 and December 2021 at the First Affiliated Hospital, Zhejiang University School of Medicine. Perioperative temperature managements were implemented for all patients included in the analysis. Estimated propensity score matching (PSM) was performed to reduce the baseline imbalances between the normothermia and hypothermia groups. Before and after PSM, univariate analyses were performed to evaluate the correlation between hypothermia and SSI. Multivariate regression analysis was performed to determine whether hypothermia was an independent risk factor for postoperative transfusion and major complications. Subgroup analyses were performed for diabetes mellitus, age > 65 years, and major liver resection. ResultsAmong 4000 patients, 2206 had hypothermia (55.2%), of which 150 developed SSI (6.8%). PSM yielded 1434 individuals in each group. After PSM, the hypothermia and normothermia groups demonstrated similar incidence rates of SSI (6.3% vs. 7.0%, P = 0.453), postoperative transfusion (13.3% vs. 13.7%, P = 0.743), and major complications (9.0% vs. 10.1%, P = 0.309). Univariate regression analysis revealed no significant effects of hypothermia on the incidence of SSI in the group with the highest hypothermia exposure [odds ratio (OR) = 1.25, 95% confidence interval (CI): 0.84-1.87, P = 0.266], the group with moderate exposure (OR = 1.00, 95% CI: 0.65-1.53, P = 0.999), or the group with the lowest exposure (OR = 1.11, 95% CI: 0.73-1.65, P = 0.628). The subgroup analysis revealed similar results. Regarding liver function, patients in the hypothermia group demonstrated lower γ-glutamyl transpeptidase (37 vs. 43 U/L, P = 0.001) and alkaline phosphatase (69 vs. 72 U/L, P = 0.016). However, patients in the hypothermia group exhibited prolonged activated partial thromboplastin time (29.2 vs. 28.6 s, P < 0.01). ConclusionsIn our study of patients undergoing liver resection, we found no significant association between mild perioperative hypothermia and SSI. It might be due to the perioperative temperature managements, especially active warming measures, which limited the impact of perioperative hypothermia on the occurrence of SSI.

Prediction of Early Atherosclerotic Plaques Using a Sequence-Activated Fluorescence Probe for the Simultaneous Detection of γ-Glutamyl Transpeptidase and Hypobromous Acid.

Atherosclerosis is a lipoprotein-driven disease, and there is no effective therapy to reverse atherosclerosis or existing plaques. Therefore, it is urgently necessary to create a noninvasive and reliable approach for early atherosclerosis detection to prevent initial plaque formation. Atherosclerosis is intimately associated with inflammation, which is accompanied by an excess of reactive oxygen species (ROS), leading to cells requiring more glutathione (GSH) to resist severe oxidative stress. Therefore, the GSH-hydrolyzed protein γ-glutamyl transpeptidase (GGT) and the ROS-hypobromous acid (HBrO) are potential biomarkers for predicting atherogenesis. Hence, to avoid false-positive diagnoses caused by a single biomarker, we constructed an ingenious sequence-activated double-locked TP fluorescent probe, C-HBrO-GGT, in which two sequential triggers of GGT and HBrO are meticulously designed to ensure that the probe fluoresces in response to HBrO only after GGT hydrolyzes the probe. By utilization of C-HBrO-GGT, the voltage-gated chloride channel (CLC-1)-HBrO-catalase (CAT)-GGT signaling pathway was confirmed in cellular level. Notably, the forthcoming atherosclerotic plaques were successfully predicted before the plaques could be observed via the naked eye or classical immunofluorescent staining. Collectively, this research proposed a powerful tool to indicate the precise position of mature plaques and provide early warning of atherosclerotic plaques.

Porta Hepatis Tuberculous Lymphadenopathy: Clinical and Imaging Features of 10 Cases

Abstract Porta hepatis tuberculous lymphadenopathy (TL) is rare, and the clinical and imaging manifestations often mimic tumors. To offer a better understanding of porta hepatis TL and thus improve its diagnosis and treatment, here, we retrospectively reviewed and analyzed 10 porta hepatis TL cases between May 2017 and November 2022. In this study, porta hepatis TL occurred predominantly in women (70%), with a mean age of 43.1 years (range, 16–70 years). Among the patients, 60% were initially suspected of malignancy (metastatic lymphadenopathy and lymphoma). The clinical manifestations were nonspecific, such as fever and weight loss, without overt abdominal malaise. Many patients showed high concentrations of serum C-reactive protein, erythrocyte sedimentation rate, alkaline phosphatase, γ-glutamyl transpeptidase and carbohydrate antigen 125. Peripheral rim-like enhancement was a characteristic finding on contrast-enhanced CT for all the patients. Pathological examination confirmed the diagnosis in 90% of patients with caseous granulomatous inflammation and positive results of Xpert MTB/RIF, quantitative real-time PCR and/or metagenomic next-generation sequencing assays. All patients underwent antituberculosis therapy with a median treatment duration of 13.5 months (range, 1–43 months). They all showed satisfactory therapeutic responses with improved symptoms and resolution on imaging after treatment. Pathological examination by biopsy remains the primary diagnostic method. A combination of the characteristic epidemiologic, clinical, imaging features and lesion biopsy for histopathology are essential for the diagnosis and treatment of TL.

Novel noninvasive indices for the assessment of liver fibrosis in primary biliary cholangitis.

The present study aimed to investigate the accuracy of new noninvasive markers in predicting liver fibrosis among individuals with primary biliary cholangitis (PBC). This retrospective analysis included subjects with PBC who had liver biopsies. Scheuer's classification was used to determine the fibrosis stage. The bilirubin to albumin (Alb) ratio (BAR), fibrosis index based on the four factors (FIB-4), γ-glutamyl transpeptidase to platelet (PLT) ratio (GPR), red cell distribution width to PLT ratio (RPR), aspartate aminotransferase (AST) to alanine aminotransferase ratio (AAR), AST to PLT ratio index (APRI) and total bilirubin to PLT ratio (TPR) were calculated based on the laboratory parameters. A novel index called BARP was conceived as BAR x RPR. A total of 78 individuals with PBC were included in the study, 84.6% of whom had significant fibrosis, 30.8% had advanced fibrosis and 15.4% had cirrhosis. In the multivariate analysis, Alb was determined to be an independent predictor of advanced fibrosis (odds ratio=0.823, P=0.034). The area under the receiver operating characteristic curves (AUROCs) of the BAR, GPR, TPR and BARP were statistically significant in predicting severe fibrosis (P<0.05) and were 0.747, 0.684, 0.693 and 0.696, respectively. In assessing advanced fibrosis, the AUROCs for the AAR, APRI, BAR, FIB-4, RPR, TPR and BARP were 0.726, 0.650, 0.742, 0.716, 0.670, 0.735 and 0.750, respectively. The AUROCs for the APRI, BAR, FIB-4, RPR, TPR and BARP for cirrhosis prediction were 0.776, 0.753, 0.821, 0.819, 0.808 and 0.832, respectively. By comparing the AUROCs, it was demonstrated that the diagnostic capabilities of the BARP (P=0.021) and TPR (P=0.044) were superior to those of the APRI in predicting advanced fibrosis. In conclusion, the BAR, BARP and TPR were of predictive value for the grade of liver fibrosis in PBC and Alb had a diagnostic value in identifying early fibrosis. The aforementioned noninvasive indices may be used for predicting histologic stages of PBC.

Noninvasive diagnosis of significant liver inflammation in patients with chronic hepatitis B in the indeterminate phase

ABSTRACT The presence of significant liver inflammation is an important indication for antiviral treatment in patients with chronic hepatitis B (CHB) in the indeterminate phase. We aimed to establish a non-invasive nomogram to predict significant liver inflammation in these patients. A total of 195 CHB patients in the indeterminate phase were randomly split into training and validation sets. The least absolute shrinkage and selection operator and logistic regression were applied to identify risk factors and establish a predictive model. A calibration curve, decision curve analysis (DCA), and receiver operating characteristic (ROC) curve were applied to assess the performance of the nomogram. The median age was 42.0 y and 59.5% of the patients were male. Alkaline phosphatase, γ-glutamyl transpeptidase, and prothrombin time were independent predictors for significant liver inflammation and selected to establish the AGP-nomogram. The calibration plot demonstrated that the predicted results matched the actual values. The DCA showed a high net benefit when the threshold probability was 25-83% in the training set and 31-100% in the validation set. The areas under ROC curves of AGP-nomogram in predicting significant inflammation were significantly higher than ALT in the training set (0.744 vs. 0.642, P = 0.049) and validation set (0.766 vs. 0.660, P = 0.047). The ability of AGP-nomogram in predicting advanced inflammation was also superior to ALT. The AGP-nomogram can accurately identify significant inflammation in CHB patients in the indeterminate phase, and its application may reduce the need for liver biopsy and help identify candidates for antiviral treatment. Abbreviations: AASLD: American Association for the Study of Liver Diseases; ALB: albumin; ALP: alkaline phosphatase; ALT: alanine aminotransferase; APRI: aspartate aminotransferase-to-platelet ratio index; AST: aspartate aminotransferase; AUROC: area under the receiver operating characteristic curve; CHB: chronic hepatitis B; CI: confidence interval; DCA: decision curve analysis; FIB-4: fibrosis index based on the four factors; GLB: globulin; GGT: γ-glutamyl transpeptidase; HBcAb: hepatitis B core antibody; HBeAg: hepatitis B e antigen; HBsAg: hepatitis B surface antigen; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HIV: human immunodeficiency virus; INR: international-normalized ratio; IQR: interquartile range; LASSO: least absolute shrinkage and selection operator; LB: liver biopsy; LR: Likelihood ratio; NAFLD: non-alcoholic fatty liver disease; NPV: negative predictive value; PLT: platelets; PPV: positive predictive value; PT: prothrombin time; ROC: receiver operating characteristic; TB: total bilirubin; TE: transient elastography; ULN: upper limit of normal.

Abstract 12727: Liver Elasticity in Elderly Heart Failure Patient

Introduction: Liver elastography is a novel ultrasound technique assessing elasticity of liver tissue. Clinical indication of liver elastography remains unrevealed. Moreover, reports about relationship between liver stiffness and heart failure subtypes haven’t well been published. Hypothesis: We have investigated the cardio-hepatic interaction using liver elastography in heart failure subtypes. Methods: We prospectively enrolled 58 consecutive patients with heart failure admission from April 2022 to March 2023. Liver elastography, transthoracic echocardiography and blood sampling were done at the time of discharge from heart failure treatment. Results: Patients were divided into two groups according to the left ventricular ejection fraction (LVEF) of echocardiography: heart failure with reduced ejection fraction (HFrEF) group (EF ≦40%, n = 11) and non-HFrEF group (EF &gt;40%, n = 31). The mean age of all patients was 83 ± 11 years. The mean age and the prevalence of hypertension and diabetes mellitus was higher in non-HFrEF group than in HFrEF group. The prevalence of taking sodium glucose co-transporter 2 (SGLT2) inhibitors was lower in non-HFrEF group than in HFrEF group. LV end-diastolic diameter, LV end-systolic diameter was larger in HFrEF group than in non-HFrEF group. Tricuspid regurgitation pressure gradient (TRPG) was higher in non-HFrEF group than in HFrEF group. Inferior vena cava diameter was not different between two groups. The mean values of almost liver function tests of all patients were within the normal range. eGFR was lower in non-HFrEF group than in HFrEF group. Liver elasticity was higher in non-HFrEF group than in HFrEF group (7.1 ± 2.7 vs. 5.1 ± 1.5 hPa; P=0.008) indicating liver stiffness. Pearson’s correlation coefficient showed that liver elasticity was positively correlated with the prevalence of diabetes mellitus, LVEF, TRPG, serum creatinine, aspartate aminotransferase, γ-glutamyl transpeptidase and was negatively correlated with LV end-diastolic diameter, LV end-systolic diameter. Conclusions: Liver stiffness was elevated in EF-preserved heart failure patients. Liver elasticity was correlated with parameters of congestion (TRPG) and useful for the assessment of congestion in patients with heart failure.

Adult Langerhans Cell Histiocytosis with Liver Involvement

Background Langerhans cell histiocytosis (LCH) is a rare, heterogeneous histiocytic disorder. We demonstrated liver involvement at baseline indicated poor survival in adult LCH in our previous study. Aims The aim of this study was to describe clinical features, liver biochemistry, radiology findings, genomic analyses, treatment approaches, and outcomes of adult LCH patients with liver involvement. Methods We conducted a retrospective analysis of all adult LCH patients (≥ 14 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022. Liver involvement by one or more of the following: either hepatomegaly, defined as a liver edge greater than 3 cm below the costal margin at the mid clavicular line, or liver dysfunction defined either by abnormal serum biochemical tests including bilirubin greater than 1.5 times the upper limit of normal, alkaline phosphatase (ALP) greater than 1.5 times the upper limit of normal, γ-glutamyl transpeptidase (GGT) greater than 1.5 times the upper limit of normal; or histopathological findings of active disease. Results Among 451 newly diagnosed adult LCH patients, 93 patients had liver involvement at diagnosis and 22 patients had liver involvement at relapse were enrolled, including 80 males (69.6%), and the median age was 32 years (range, 15-66 years). 111 of 115 patients had full liver function test. 70 patients (63.1%) had elevated ALP; 96 patients (86.5%) had elevated GGT, and the median level was 157 U/L (range, 14-2249 U/L); 16 patients (14.4%) had elevated total bilirubin, and the median level was 12.5 umol/L (range, 1.7-248.1umol/L); Among 48 patients who had sufficient DNA for next-generation sequencing, BRAFV600E (20.8%), BRAFN486_P490 (37.5%) and MAP2K1(12.5%) were the most common alternations. In total, 99 patients (86.1%) received first-line systematic treatment, including 76 patients who received chemotherapies (methotrexate/cytarabine regimens, cytarabine monotherapy, vindesine/prednisone-based regimens, cladribine monotherapy and corticosteroid), 15 patients who received immunomodulatory drugs (IMiDs) therapies (thalidomide/cyclophosphamide/dexamethasone regimens and lenalidomide/dexamethasone regimens) and 8 patients who received target therapies (BRAF inhibitors and MEK inhibitors). After a median 39-month follow-up (range 1-168 months), thirteen patients died during follow-up. The estimated 3-year OS rate was 85.5%. 44 patients had disease progression. The median PFS duration was 31.4 months. Nine patients got cirrhosis during follow-up and 2 patients underwent liver transplantation. Univariate analysis was performed to evaluate the prognostic factors of OS and PFS. Patients with elevated total bilirubin at baseline had significantly shorter OS and PFS. Patients who had 3 or more abnormal serum live function tests (including ALT, AST, ALP, GGT, total bilirubin and ALB), and patients with elevated high sensitive C reactive protein (hsCRP) had significantly shorter PFS. Patients who received target therapy or iMIDs-based therapy had significantly longer PFS than patients who received other systemic treatments. In multivariable analyses, Patients who had 3 or more abnormal serum live function tests (HR 2.652, 95% CI 1.256-5.602), and treatment with iMIDs (HR 0.076, 95% CI 0.010-0.564) remained predictive factors for PFS. Conclusion Adult LCH patients with liver involvement most had elevated GGT and ALP. Elevated hsCRP and 3 or more abnormal live function tests predict poor outcomes. Target therapy or iMIDs-based therapy showed better outcomes.

Prediction model for hepatocellular carcinoma recurrence after hepatectomy: Machine learning-based development and interpretation study

BackgroundIdentifying patients with hepatocellular carcinoma (HCC) at high risk of recurrence after hepatectomy can help to implement timely interventional treatment. This study aimed to develop a machine learning (ML) model to predict the recurrence risk of HCC patients after hepatectomy. MethodsWe retrospectively collected 315 HCC patients who underwent radical hepatectomy at the Third Affiliated Hospital of Sun Yat-sen University from April 2013 to October 2017, and randomly divided them into the training and validation sets at a ratio of 7:3. According to the postoperative recurrence of HCC patients, the patients were divided into recurrence group and non-recurrence group, and univariate and multivariate logistic regression were performed for the two groups. We applied six machine learning algorithms to construct the prediction models and performed internal validation by 10-fold cross-validation. Shapley additive explanations (SHAP) method was applied to interpret the machine learning model. We also built a web calculator based on the best machine learning model to personalize the assessment of the recurrence risk of HCC patients after hepatectomy. ResultsA total of 13 variables were included in the machine learning models. The multilayer perceptron (MLP) machine learning model was proved to achieve optimal predictive value in test set (AUC = 0.680). The SHAP method displayed that γ-glutamyl transpeptidase (GGT), fibrinogen, neutrophil, aspartate aminotransferase (AST) and total bilirubin (TB) were the top 5 important factors for recurrence risk of HCC patients after hepatectomy. In addition, we further demonstrated the reliability of the model by analyzing two patients. Finally, we successfully constructed an online web prediction calculator based on the MLP machine learning model. ConclusionMLP was an optimal machine learning model for predicting the recurrence risk of HCC patients after hepatectomy. This predictive model can help identify HCC patients at high recurrence risk after hepatectomy to provide early and personalized treatment.

Dogs’ general response to babesiosis infection of various severities

Global climate change in recent decades has led to an increase in the activity and expansion of the range of many diseases. One of them is canine babesiosis. Therefore, it is becoming increasingly important to monitor the functional state of the organism in sick dogs and timely detection of kidney, liver, spleen, cardiovascular system, anaemia, and other disorders that complicate the course of babesiosis. The research aims to determine the peculiarities of metabolic and functional changes in dogs with different intensities of babesiosis infection. During the laboratory diagnostics, general and special research methods were used: light microscopy, centrifugation, spectrophotometry, and mathematical statistics. Based on the results of comprehensive microscopic, morphological, and biochemical studies of blood in dogs with different intensities of babesiosis infection, the most characteristic functional and metabolic changes in their body were identified. Thus, at different intensities of babesiosis infection in diseased animals, the features of the haematological profile are leukocytopenia against the background of eosinopenia (at a mild degree of infection) and lymphocytopenia with a simultaneous compensatory increase in the number of monocytes and neutrophils, as well as erythrocytopenia, hypochromemia, thrombocytopenia with a decrease in thrombocrit and haematocrit. In addition, these patients developed hyperfermentemia of aspartate and alanine aminotransferases, alkaline phosphatase, and γ-glutamyl transpeptidase, indicating structural and functional changes, primarily in the myocardium, liver, skeletal muscle, brain and kidneys due to their toxic damage by babesia waste products. At the same time, hypoproteinaemia, hypoalbuminemia and hyperazotemia were observed in the affected animals, indicating an increase in the intensity of catabolic processes in functional cells of organs and tissues, especially the liver. The most pronounced changes in the studied parameters were observed at high intensity of babesiosis infection. The established regularities allow the use of these haematological parameters as markers of functional and metabolic changes in the body of dogs at different intensities of babesiosis infection

A multiserological line assay to potentially discriminate current from past Helicobacter pylori infection

ObjectivesEarly diagnosis is important in controlling Helicobacter pylori-induced gastritis and progression to gastric malignancy. Serological testing is an efficient non-invasive diagnostic method, but currently does not allow differentiation between active and past infections. To fill this diagnostic gap we investigated the diagnostic value of a panel of ten H. pylori-specific antibodies in individuals with different H. pylori infection status within a German population. MethodsWe used the recomLine Helicobacter IgG 2.0 immunoblotting assay to analyse ten H. pylori-specific antibodies in serum samples collected from 1108 volunteers. From these, 788 samples were used to build exposure and infection status models and 320 samples for model validation. H. pylori infection status was verified by histological examination. We applied logistic regression to select antibodies correlated to infection status and developed, with independent validation, discriminating models and risk scores. Receiving operating characteristic analysis was performed to assess the accuracy of the discriminating models. ResultsAntibody reactivity against cytotoxin-associated gene A (CagA), H. pylori chaperone (GroEL), and hook-associated protein 2 homologue (FliD) was independently associated with the risk of H. pylori exposure with ORs and 95% CIs of 99.24 (46.50–211.80), 46.17 (17.45–122.17), and 22.16 (8.46–55.04), respectively. A risk score comprising these three selected antibodies differentiated currently H. pylori infected or eradicated participants from negatives with an area under the curve of 0.976 (95% CI: 0.965–0.987) (Model 1). Seropositivity for vacuolating cytotoxin A (VacA), GroEL, FliD, H. pylori adhesin A (HpaA), and γ-glutamyl transpeptidase (gGT) was associated with a current infection with an area under the curve of 0.870 (95% CI: 0.837–0.903), which may help discriminate currently infected patients from eradicated ones (Model 2). DiscussionThe recomLine assay is sensitive and specific in determining H. pylori infection and eradication status and thus represents a valuable tool in the management of H. pylori infection.

Associations of serum alkaline phosphatase level with all-cause and cardiovascular mortality in the general population.

There are few population studies on the associations of serum alkaline phosphatase (AlkP) with all-cause and cardiovascular mortality. We aimed to investigate the relevancy of serum AlkP with all-cause and cardiovascular mortality in the general population. Our research included 34,147 adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Cox proportional hazards regression models were used to assess the associations of serum AlkP with all-cause and cardiovascular mortality. Mediation analysis was used to analyze mechanisms that might link serum AlkP to all-cause and cardiovascular mortality. After 139.7 ± 57.8 months of follow-up, 5413 participants experienced all-cause death and 1820 participants experienced cardiovascular death. Mortality rates per 1000 person-years from various diseases increased with increasing serum concentrations of AlkP, especially all-cause death, cerebrovascular disease and cardiovascular death. High serum AlkP level significantly increased all-cause and cardiovascular mortality. After multivariate adjustment, the highest AlkP group had the highest risk to experience all-cause (hazard ratio [HR] = 1.30, P < 0.001) and cardiovascular mortality (HR = 1.39, P < 0.001) than the lowest AlkP group. γ-glutamyl transpeptidase (GGT) (13.33% and 15.79%), followed by Vitamin D (8.33% and 7.14%) and C-reactive protein (CRP) (7.69% and 10.35%) were identified as possible major mediators. Higher AlkP concentrations were associated with higher all-cause and cardiovascular mortality, largely related to mediated factors such as GGT, Vitamin D, and CRP. These findings suggest that lower serum AlkP level may reduce all-cause and cardiovascular mortality in general population.

γ-Glutamyl transpeptidase activatable probe for fluorescence-assisted guiding surgery and imaging of human tumors via spraying

γ-Glutamyltranspeptidase (GGT) is an ectoenzyme anchored on the surface of the cell membrane, and it is closely associated with many diseases. Abnormal expression (>36 U/L) of GGT is involved in the progression of tumors and can act as a biomarker for tumor diagnosis. Here, we presented a series of GGT-activatable fluorescent probes, the P1, the P2 and the P3. By investigating the in vitro properties of the probes, P3 demonstrated the most sensitivity and better water solubility, which benefited from the introduction of the self-elimination moiety of p-aminobenzyl alcohol and the propanesulfonic acid moiety. Importantly, P3 was able to clearly delineate tumor boundaries in live tumor-bearing mice and clinical human liver tissue specimens by spraying in situ, which facilitated accurate resection of tumors under fluorescence guidance. The proposed enzyme-activated fluorescent probe has potential as a surgical resection tool in image-guided surgery.

Near-infrared imaging of hepatocellular carcinoma and its medicinal treatment with a γ-glutamyl transpeptidase-monitoring fluorescence probe

Herein, the Near-infrared imaging of hepatocellular carcinoma (HCC) and its medicinal treatment was achieved with a γ-glutamyl transpeptidase (GGT)-monitoring fluorescence probe KYZ-GGT which consisted of the typical recognition group γ-glutamyl and the structurally modified signal reporting group hemicyanine-thioxanthene. Compared with the recently reported probes, KYZ-GGT suggested practical and steady capability for monitoring the GGT level in the cellular, xenograft, induced as well as medicinal treatment HCC models. It realized the mitochondrial targeting intracellular imaging to reflect the GGT dynamics in the induction or medicinal treatment of HCC. In the xenograft and induced model mice with multiple factors, KYZ-GGT showed stable performance for visualizing the HCC status. In the medicinal treatment of the long-period-induced HCC model mice verified by the serum indexes and histopathological analysis, KYZ-GGT successfully imaged the medicinal treatment process of HCC with two marketed drugs (Sorafenib and Lenvatinib) respectively, with an applicative penetration depth. The information here was meaningful for investigating effective medicinal strategies for overcoming HCC.

EFFICACY OF OSTEOPATHIC TREATMENT OF PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE IN SANATORIUM AND RESORT CONDITIONS

Background. The relevance of the problem of treating patients with non-alcoholic fatty liver disease dictates the need to find new approaches to such patients' treatment. Aim. Evaluation of the eZectiveness of the combined use of sanatorium-resort and osteopathic methods of treating patients with non-alcoholic fatty liver disease in sanatorium-resort conditions.Research Objectives. To study the dynamics of health complaints patients with non-alcoholic fatty liver disease during the treatment. Investigate the changes in blood biochemical parameters (ALT, AST, GGT) in patients before and after the treatment. To assess the osteopathic status in patients with non-alcoholic fatty liver disease. To evaluate the effectiveness of the patient treatment according to the SF-36 quality-of-life questionnaire. Materials and Methods. On the basis of St. Petersburg Institute for Advanced Training of Medical Examiners and Clinic "Kivach" (Republic of Karelia), 24 patients of different sexes aged about about 36.4±3.6 years who were undergoing the program "General rehabilitation — 14 days" at the clinic's sanatorium due to non-alcoholic fatty liver disease were examined. Upon arrival at the sanatorium, all patients had their body mass index (BMI) calculated, ultrasound of the abdominal organs and examination for hepatitis B and C markers were performed; the general health condition was assessed, biochemical blood parameters were monitored (liver enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transpeptidase (GGT) before the treatment, immediately after the treatment in the sanatorium and after 3 months (at the place of residence). The patients' life quality was investigated with the SF-36 questionnaire [1]. The osteopathic examination included an assessment of musculoskeletal, craniosacral and visceral systems according to the generally accepted schemes and was carried out differentially depending on the biomechanical disorders found [2]. The osteopathic treatment of the patients was carried out for 40 minutes 2 times a week. Results. The high efficiency of the combined use of sanatorium-resort and osteopathic methods of treating patients with nonalcoholic fatty liver disease in sanatorium-resort conditions was identified. Conclusions. After the course of the combined treatment of the patients in the sanatorium, there is a significant improvement of subjective state indicators (health complaints), normalization of biochemical (liver) blood parameters and osteopathic status. In 3 months after the treatment of the patients, favorable changes in the above-mentioned indicators are more expressed. The effectiveness of the treatment of the patients with non-alcoholic fatty liver disease in sanatorium-resort conditions is confirmed by the positive dynamics of the indicators of physical and psychological components of the health quality of life according to the SF-36 questionnaire.

Reconstructing hepatic metabolic profile and glutathione-mediated metabolic fate of acrylamide

The toxicity of acrylamide (AA) has continuously attracted wide concerns as its extensive presence from both environmental and dietary sources. However, its hepatic metabolic transformation and metabolic fate still remain unclear. This study aims to unravel the metabolic profile and glutathione (GSH) mediated metabolic fate of AA in liver of rats under the dose-dependent exposure. We found that exposure to AA dose-dependently alters the binding of AA and GSH and the generation of mercapturic acid adducts, while liver as a target tissue bears the metabolic transformation of AA via regulating GSH synthesis and consumption pathways, in which glutamine synthase (GSS), cytochrome P450 2E1 (CYP2E1), and glutathione S-transferase P1 (GSTP1) play a key role. In response to high- and low-dose exposures to AA, there were significant differences in liver of rats, including the changes in GSH and cysteine (CYS) activities and the conversion ratio of AA to glycidamide (GA), and liver can affect the transformation of AA by regulating the GSH-mediated metabolic pathway. Low-dose exposure to AA activates GSH synthesis pathway in liver and upregulates GSS activity and CYS content with no change in γ-glutamyl transpeptidase 1 (GGT1) activity. High-dose exposure to AA activates the detoxification pathway of GSH and increases GSH consumption by upregulating GSTP1 activity. In addition, molecular docking results showed that most of the metabolic molecules transformed by AA and GA other than themselves can closely bind to GSTP1, GSS, GGT1, N-acetyltransferase 8, and dimethyl sulfide dehydrogenase 1. The binding of AA-GSH and GA-GSH to GSTP1 and CYP2E1 enzymes determine the tendentiousness between toxicity and detoxification of AA, which exerts a prospective avenue for targeting protective role of hepatic enzymes against in vivo toxicity of AA.