Γ-glutamyl Transpeptidase Levels Research Articles

7055 Metabolic Disorders In Thalidomide Embryopathy

Abstract Disclosure: A. Tanabe: None. Thalidomide embryopathy (TE) is a congenital limb defect that occurs in neonates born to pregnant women who have taken thalidomide. Typical abnormalities of the TE are upper limb hypoplasia and and/or auditory dysfunction. In Japan, thalidomide was marketed as an agent for sleep-induce and digestive ulcers from 1958 to 1962. Up to now, approximately 290 cases have been certified and are supported by the government as drug-induced disease. Currently, many of the victims are in their late 50s, and in addition to congenital disabilities, various health issues such as lifestyle-related diseases can be developed. We investigated their metabolic condition using data of medical health checkup between 2017 and 2018. Fifty-one Japanese cases of TE (28 men and 23 women) were included in this study. The mean age was 56.4±1.6 years in men and 55.9±1.2 years in women. The prevalence of upper limb deformities was 64% in men and 74% in women; the remaining patients had only hearing impairment. The mean body mass index (BMI) was 22.7±2.1 in men and 22.5±4.0 in women. Eleven percent of men and 17% of women had a BMI between 25-30, while 9% of women and no men had a BMI of 30 or greater. Liver dysfunction was seen in 32% of men and 9% of women. The mean high-density lipoprotein cholesterol level was 60±17 mg/dL in men and 68±18 mg/dL in women. The mean low-density lipoprotein (LDL) cholesterol level was 120±28 mg/dL in men and 136±35 mg/dL in women, with 25% of men and 48% of women had LDL level of 140 mg/dL or greater. The mean triglyceride (TG) level was 144±85 mg/dL in men and 116±61 mg/dL in women, with 43% of men and 17% of women had a level of 150 mg/dL or greater. The mean HbA1c level was 6.0±1.0% in men and 5.9±0.4% in women. The prevalence of impaired glucose tolerance was 25% in men and 13% in women. Fatty liver (FL) evaluated by ultrasonography or CT scan was 61% in men and 39% in women. The patients with FL showed significantly high body fat percentage and TG level in men, high alanine aminotransferase, γ-glutamyl transpeptidase and TG levels in women, respectively, compared to the patients without FL. The prevalence of hypertriglyceridemia was significantly higher in men with FL compared with men without FL. There was no significant difference in with or without the upper limb abnormalities in both groups. Although without obvious overweight, more than 40 % of the patients had dyslipidemia and 50% of the patients had FL. The limb abnormalities can result in movement limitations however other factors may be involved in the development of metabolic disorders in TE. The results of this study provide valuable information for future health management in thalidomide embryopathy. (This study was conducted by a research grant from the National Center for Global Health and Medicine, Japan: 21A1015 and a Grant-in-Aid from the Ministry of Health, Labour, and Welfare, Japan: 20KC2005, 23KC2017). Presentation: 6/2/2024

Guidance for the occupational medicine service regarding the prevention of hepatitis C and HIV infection in Poland

The set up of new healthcare models by taking into account diagnosis and health education of the viral infection, aims to achieve the goals of the World Health Organization Global Health Sector Strategy on viral diseases for 2022-2030. In comparison to Europe, Poland is ranked among countries with an moderate prevalence of hepatitis B and C virus (HBV and HCV), also human immunodeficiency virus (HIV). An additional challenge is the changing epidemiological situation due to the impact of immigrants, resulting mainly from the war in Ukraine. The article presents current guidance for HCV and HIV diagnosis and presents the role of occupational health service (OHS) for primary and secondary prevention of the infectious diseases. It was considered to expand the scope of periodic examinations to include diagnosis of HBV, HCV and HIV infections among health care workers, who have not had it performed so far. In the case of abnormal level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or γ-glutamyl transpeptidase (GGT) found during routine pre-employment or periodic examinations for specific occupational exposures and it is considered crucial to implement further measures to exclude or confirm HBV or HCV infection, with indications for further management in primary care, and followed by subsequent periodic examinations. The need to pay attention to any symptoms that may indicate HBV, HCV and/or HIV infection, to perform additional diagnostic tests (e.g., point of care), and to determine the next steps in case of positive result was indicated. It emphasized the need to tailor the delivery of information to the patient, including taking care to ensure that immigrants' workers understand the next steps. It was recommended that the OHS conduct educational activities to raise health awareness of HIV, HCV, HBV infections, both through health policy programs as well as through broader activities in cooperation with the employer. Med Pr Work Health Saf. 2024;75(5).

Clinical features, treatment, and outcome of nivolumab-induced cholangitis

Background Cholangitis is an uncommon and severe adverse reaction of nivolumab with unclear clinical features. The purpose of this study was to investigate the clinicopathological features, imaging, and treatment of nivolumab-induced cholangitis. Methods Case reports, case series, and clinical studies of nivolumab-induced cholangitis were retrospectively analyzed by searching Chinese and English databases from January 1, 2017 to December 31, 2023. Results Thirty-eight patients entered the study. The median number of cycles of cholangitis onset was seven cycles after administration (range 1, 28) and the median time was 11 days (range 78, 390). Abdominal pain (42.1%) and fever (18.4%) were the most important initial symptoms. Some patients (15.8%) showed elevated liver enzymes without any clinical symptoms. The median alkaline phosphatase level was 1721 IU/L (range 126, 9118), and the median γ-glutamyltranspeptidase level was 829 IU/L (range 104, 3442). Anti-nuclear antibodies, anti-mitochondrial antibodies, and IgG4 typically show negative results. Imaging shows extrahepatic bile duct and intrahepatic bile duct dilation, hypertrophy, and stenosis. Liver biopsy and biliary tract biopsy mainly found CD8 inflammatory cell infiltration. Systemic steroids (84.2%) and ursodeoxycholic acid (UDCA) (34.2%) were administered, and 24 patients (63.2%) had poor to moderate response to steroids. Thirty-one patients (81.6%) improved and seven patients (18.4%) did not improve. Conclusions Clinicians must remain vigilant for patients experiencing cholestasis while on nivolumab and should assess for cholangitis and carry out appropriate imaging tests. Considering the excellent efficacy of UCDA in cholangitis, steroids combined with UDCA may be a viable treatment option in cases where steroids are ineffective for cholangitis.

Depressive symptom as a risk factor for cirrhosis in patients with primary biliary cholangitis: Analysis based on Lasso-logistic regression and decision tree models.

Depressive symptoms are frequently observed in patients with primary biliary cholangitis (PBC). The role of depressive symptoms on cirrhosis has not been fully noticed in PBC. We aimed to establish a risk model for cirrhosis that took depressive symptoms into account. Depressive symptoms were assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17). HAMD-17 score was analyzed in relation to clinical parameters. Least absolute shrinkage and selection operator (Lasso)-logistic regression and decision tree models were used to explore the effect of depressive symptoms on cirrhosis. The rate of depressive symptom in patients with PBC (n=162) was higher than in healthy controls (n=180) (52.5%vs. 16.1%; p<.001). HAMD-17 score was negatively associated with C4 levels and positively associated with levels of alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TB), Immunoglobulin (Ig) G, and IgM (r=-0.162, 0.197, 0.355, 0.203, 0.182, 0.314, p<.05). In Lasso-logistic regression analysis, HAMD-17 score, human leukocyte antigen (HLA)-DRB1*03:01 allele, age, ALP levels, and IgM levels (odds ratio [OR]=1.087, 7.353, 1.075, 1.009, 1.005; p<0.05) were independent risk factors for cirrhosis. Elevated HAMD-17 score was also a discriminating factor for high risk of cirrhosis in patients with PBC in decision tree model. Depressive symptoms were associated with disease severity. Elevated HAMD-17 score was a risk factor for cirrhosis in patients with PBC.

Precise risk-prediction model including arterial stiffness for new-onset atrial fibrillation using machine learning techniques.

Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia and is an important risk factor for ischemic cerebrovascular events. This study used machine learning techniques to develop and validate a new risk prediction model for new-onset AF that incorporated the use electrocardiogram to diagnose AF, data from participants with a wide age range, and considered hypertension and measures of atrial stiffness. In Japan, Industrial Safety and Health Law requires employers to provide annual health check-ups to their employees. This study included 13 410 individuals who underwent health check-ups on at least four successive years between 2005 and 2015 (new-onset AF, n=110; non-AF, n=13 300). Data were entered into a risk prediction model using machine learning methods (eXtreme Gradient Boosting and Shapley Additive Explanation values). Data were randomly split into a training set (80%) used for model construction and development, and a test set (20%) used to test performance of the derived model. The area under the receiver operator characteristic curve for the model in the test set was 0.789. The best predictor of new-onset AF was age, followed by the cardio-ankle vascular index, estimated glomerular filtration rate, sex, body mass index, uric acid, γ-glutamyl transpeptidase level, triglycerides, systolic blood pressure at cardio-ankle vascular index measurement, and alanine aminotransferase level. This new model including arterial stiffness measure, developed with data from a general population using machine learning methods, could be used to identify at-risk individuals and potentially facilitation the prevention of future AF development.

Liver enzyme profiles after initiating biological treatment in children with inflammatory bowel diseases.

Biological treatments (BTs) are essential in managing pediatric inflammatory bowel diseases (PIBDs). Elevated liver enzymes sometimes succeed BT, yet elucidating studies are scarce. We addressed liver biochemistry after introducing BT and searched for their determinants. We identified PIBD patients receiving infliximab, adalimumab, vedolizumab, or ustekinumab at the Children's Hospital, University of Helsinki, Finland, in 2000-2023, and followed their alanine transaminase (ALT) and γ-glutamyl transpeptidase (GT) levels for 24 months. ALT was categorized based on the age- and sex-specific upper limit of normal. We disregarded 46 patients with underlying primary sclerosing cholangitis with/without autoimmune hepatitis (AIH), pretreatment AIH diagnosis, and elevated liver enzymes at the beginning of BT from the analyses. Of 618 BT episodes in 403 patients, 22.2% exhibited increased ALT or GT (ALT in 117, GT in 4, and both ALT/GT in 16 episodes). Of all ALT elevations (n = 133), 41.4% occurred within the first 3 months. ALT elevation was more common after infliximab (representing 59.5% of BTs) than other BTs (25.9% vs. 14.2%, adjusted odds ratio [OR]: 2.41, 95% confidence interval [CI]: 1.23-4.72). AIH followed 1.5% (n = 9) of BT episodes. Ninety-five percent of ALT elevations resolved within 6 months. Antibiotic exposure (particularly to metronidazole) was associated with ALT elevation in general (adjusted OR: 5.76, 95% CI: 2.40-13.9) and short disease duration before starting BT with notable ALT elevation (adjusted OR: 1.10, 95% CI: 1.01-1.22). Benign ALT elevation is common within 3 months after starting BT (especially infliximab) and scarcely led to cessation of the treatment. AIH is a rare finding during the first year of BT.

Development of a novel nomogram for predicting delayed methotrexate excretion following high-dose methotrexate in adult patients with hematologic malignancies.

High-dose methotrexate (HDMTX) is integral in treating hematologic malignancies but carries risks of severe toxicities due to prolonged MTX exposure. However, knowledge of delayed MTX excretion is primarily derived from pediatric and adolescent cohorts, with the reported predictors being presented as rough dichotomous values. This study aimed to identify risk factors for delayed MTX excretion exclusively in adult patients with hematologic malignancies and develop a more applicable predictive nomogram based on continuous clinical and laboratory variables. 517 HDMTX cycles in 194 patients were retrospectively analyzed. Delayed MTX excretion was defined as either MTX concentration ≥ 1.0 µmol/L at 48h or ≥ 0.1 µmol/L at 72h after HDMTX initiation. Multivariate logistic regression analysis was used to construct the nomogram internally validated with the bootstrap method. Delayed MTX excretion was observed in 24.0% of cycles. Six significant predictors were identified: relapsed/refractory disease (Odds ratio [OR] 2.03), fewer HDMTX cycles (OR 0.771), treatment intent (OR 2.13), lower albumin (OR 0.563) and creatinine clearance levels (OR 0.993), and increased γ-glutamyl transpeptidase levels (OR 1.004, all P < 0.05). These were incorporated into a web-based nomogram as continuous variables with good prediction accuracy (area under the curve, 0.73) and without significant overfitting. Delayed MTX excretion increased risks of developing acute kidney injury, even solely at the 72h timepoint (OR 2.57, P = 0.025), without providing any benefit of clinical outcomes. This study comprehensively characterized MTX elimination failure following HDMTX in adult patients and could pave the way for individualized risk prediction.

Clinical characteristics and natural history of porto-sinusoidal vascular disease: A cohort study of 234 patients in China.

Porto-sinusoidal vascular disease (PSVD) is an under-recognized and under-diagnosed disease. The purpose of this study was to investigate the clinical features and prognosis of PSVD. The patients who underwent liver biopsies were analyzed retrospectively. The clinical and pathological data were reviewed and screened according to the latest diagnostic criteria of PSVD. A total of 234 patients were diagnosed as PSVD, including 103 patients presented with portal hypertension (PH) and 131 patients without PH. At baseline, the alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT) levels were higher in the no-PH group. The liver stiffness increased in the PH group. In histological review, obliterative portal venopathy, sinusoidal dilatation and architectural disturbance were more common in the PH group, while portal tract abnormalities were more widely distributed in the no-PH group. After a median follow-up of 43.6 months, the survival rate of patients with baseline liver decompensation was 76.0%, and that of patients at a liver compensated stage in the PH group was 98.7%. First variceal bleeding occurred in 13.8% of patients with gastric-oesophageal varices. None of the patients in the no-PH group developed portal hypertension during follow-up. PSVD can manifest as PH or mild liver enzyme abnormalities. There are significant differences in pathological features among patients with different clinical manifestations. Recurrent ascites are the main cause of death in PSVD patients. However, patients without PH have a slow disease progression, with recurrent elevated GGT levels being their main clinical feature.

Effect of sustained decreases in sedentary time and increases in physical activity on liver enzymes and indices in type 2 diabetes.

Current guidelines for nonalcoholic fatty liver disease (NAFLD) recommend high volumes and/or intensities of physical activity (PA), the achievement of which generally requires participation in supervised exercise training programs that however are difficult to implement in routine clinical practice. Conversely, counselling interventions may be more suitable, but result in only modest increases in moderate-to-vigorous-intensity PA (MVPA). This study assessed whether a counseling intervention for increasing PA and decreasing sedentary time (SED-time) is effective in improving NAFLD markers in people with type 2 diabetes. Three-hundred physically inactive and sedentary patients were randomized 1:1 to receive one-month theoretical and practical counseling once-a-year (intervention group) or standard care (control group) for 3 years. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltranspeptidase (γGT) levels were measured and fatty liver index (FLI), hepatic steatosis index (HSI), and visceral adiposity index (VAI) were calculated. Total PA volume, light-intensity PA (LPA), moderate-to-vigorous-intensity PA (MVPA), and SED-time were objectively measured by an accelerometer. Throughout the 3-year period, NAFLD markers did not change in the control group, whereas ALT, γGT, FLI, and HSI decreased in the intervention group, with significant between-group differences, despite modest MVPA increases, which however were associated with larger decrements in SED-time and reciprocal increments in LPA. Mean changes in NAFLD markers varied according to quartiles of (and correlated with) changes in MVPA (all markers) and SED-time, LPA, and PA volume (ALT, γGT, and HSI). Mean changes in MVPA or PA volume were independent predictors of changes in NAFLD markers. When included in the models, change in cardiorespiratory fitness and lower body muscle strength were independently associated with some NAFLD markers. A behavior change involving all domains of PA lifestyle, even if insufficient to achieve the recommended MVPA target, may provide beneficial effects on NAFLD markers in people with type 2 diabetes.

Exposure to synthesized tribromobisphenol A and critical effects: Metabolic pathways, disease signature, and benchmark dose derivation

2,2′,6-Tribromobisphenol A (Tri-BBPA), the main debrominated congener of tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and human body but with unknown toxicity. Tri-BBPA was synthesized and applied to investigate its sub-chronic exposure effects on 28 organ coefficients and clinical health indicators related to liver function, kidney function, and cardiovascular system function in female mice. Results showed that the liver was the targeted organ of Tri-BBPA exposure. Compared to the control group, the changes in liver coefficient, cholinesterase, total protein, albumin, γ-glutamyl transpeptidase, lactate dehydrogenase, and creatine kinase levels ranged from −61.2 % to 35.5 % in the high-exposed group. Creatine kinase was identified as a critical effect indicator of Tri-BBPA exposure. Using the Bayesian benchmark dose derivation method, a lower reference dose than TBBPA was established for Tri-BBPA (10.6 μg/kg-day). Serum metabolomics revealed that Tri-BBPA exposure may primarily damage the liver by disrupting tryptophan metabolism related to L-alanine, tryptamine, 5-hydroxyindoleacetic acid, and 5-methoxyindoleacetate in liver cells and leading to liver dysfunction. Notably, epilepsy, schizophrenia, early preeclampsia, and late-onset preeclampsia were the top six enriched diseases, suggesting that the nervous system may be particularly affected by Tri-BBPA exposure. Our findings hinted a non-negligible health risk of exposure to debrominated products of TBBPA.

Epidemiology of Fontan-associated liver disease in Japan: Results from a nationwide survey in 2021.

Although the Fontan procedure has improved the survival of patients with single-ventricle heart disease, the long-term consequences of the procedure have been a concern. This study aimed to explore the patients' postoperative clinical characteristics, including a diagnosis of Fontan-associated liver disease (FALD). A nationwide Japanese epidemiological survey of post-Fontan patients was undertaken in 2021. The survey targets were selected from all departments of pediatrics, pediatric surgery, cardiology, cardiovascular surgery, and gastroenterology using stratified random sampling by the number of beds. Each department was asked to complete a mail-back questionnaire on the numbers of patients and their clinical characteristics. The diagnosis of FALD was made by each attending physician. The estimated number of post-Fontan patients was 7810 (95% confidence interval, 5430-10200) in 2020, with a period prevalence of 61.9 per million. During the follow-up of 13.8years after the Fontan procedure, 40% of patients were diagnosed with FALD. An elevated γ-glutamyl transpeptidase level was the most common finding leading to the FALD diagnosis (41%), and 45% of the patients also showed liver fibrosis. Compared with non-FALD patients, FALD patients were older, had longer duration since the Fontan procedure, and had more severe cardiac or liver conditions. However, more than half of the non-FALD patients had elevated liver enzyme levels, suggesting underestimation of the number of FALD patients. In 2020, approximately 40% of post-Fontan patients underwent follow-up with a diagnosis of FALD, although the lack of established diagnostic criteria for FALD could affect the reported prevalence of FALD.

Predictive value of bilirubin and serum γ-glutamyltranspeptidase levels in type-2 diabetes mellitus patients with acute coronary syndrome.

Cardiovascular disease is a major complication of diabetes mellitus (DM). Type-2 DM (T2DM) is associated with an increased risk of cardiovascular events and mortality, while serum biomarkers may facilitate the prediction of these outcomes. Early differential diagnosis of T2DM complicated with acute coronary syndrome (ACS) plays an important role in controlling disease progression and improving safety. To investigate the correlation of serum bilirubin and γ-glutamyltranspeptidase (γ-GGT) with major adverse cardiovascular events (MACEs) in T2DM patients with ACS. The clinical data of inpatients from January 2022 to December 2022 were analyzed retrospectively. According to different conditions, they were divided into the T2DM complicated with ACS group (T2DM + ACS, n = 96), simple T2DM group (T2DM, n = 85), and simple ACS group (ACS, n = 90). The clinical data and laboratory indices were compared among the three groups, and the correlations of serum total bilirubin (TBIL) levels and serum γ-GGT levels with other indices were discussed. T2DM + ACS patients received a 90-day follow-up after discharge and were divided into event (n = 15) and nonevent (n = 81) groups according to the occurrence of MACEs; Univariate and multivariate analyses were further used to screen the independent influencing factors of MACEs in patients. The T2DM + ACS group showed higher γ-GGT, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and glycosylated hemoglobin (HbA1c) and lower TBIL and high-density lipoprotein cholesterol levels than the T2DM and ACS groups (P < 0.05). Based on univariate analysis, the event and nonevent groups were significantly different in age (t = 3.3612, P = 0.0011), TBIL level (t = 3.0742, P = 0.0028), γ-GGT level (t = 2.6887, P = 0.0085), LDL-C level (t = 2.0816, P = 0.0401), HbA1c level (t = 2.7862, P = 0.0065) and left ventricular ejection fraction (LEVF) levels (t=3.2047, P = 0.0018). Multivariate logistic regression analysis further identified that TBIL level and LEVF level were protective factor for MACEs, and age and γ-GGT level were risk factors (P < 0.05). Serum TBIL levels are decreased and γ-GGT levels are increased in T2DM + ACS patients, and the two indices are significantly negatively correlated. TBIL and γ-GGT are independent influencing factors for MACEs in such patients.

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.

Comparison of the efficacy and safety of hypoglycemic treatments in patients with non-alcoholic fatty liver disease and type-2 diabetes: a systematic review and Bayesian network analysis.

The association between non-alcoholic fatty liver disease (NAFLD) and metabolic disorders, especially type-2 diabetes (T2DM), has been proven to be bidirectional. Hypoglycemic agents may be promising treatments for those disorders. However, there is currently no approved hypoglycemic therapy for NAFLD. In this review, we aimed to compare the efficacy and safety of twelve different hypoglycemic treatments in patients with NAFLD and T2DM. We systematically screened randomized controlled trials (RCTs) published from March 2013 to March 2023 by searching PubMed, Embase, Medline, and Web of Science without any language restriction. We registered this project on the PROSPERO website: https://www.crd.york.ac.uk/PROSPERO/ (ID: CRD42023429701). All subsequent analyses were performed under the registered protocol. The mean difference (MD) and 95% confidence interval (95% CI) were adapted to evaluate the effect size of the treatment. The surface under the cumulative sorting curve (SUCRA) was used to rank the efficacy of the included treatments. We included 19 trials involving 1212 patients in total. Insulin plus glucagon-like peptide-1 receptor agonist (GLP1RA) combination therapy was probably the most effective treatment for reducing weight and body mass index (BMI) (SUCRA: 0.93 and 1.00). Thiazolidinediones (TZD) were probably the most effective treatment for reducing glycosylatedhemoglobin (HbA1c) and γ-glutamyltranspeptidase (γ-GGT) levels (SUCRA: 0.78 and 0.97). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) had the highest probability of presenting good therapeutic efficacy in reducing triglyceride (TG) levels (SUCRA: 0.72). The most common adverse reactions were gastrointestinal disorders, mainly after the administration of GLP1RA, and mild hypoglycemia, which was closely related to the use of insulin. GLP1RA plus insulin combination therapy, GLP1RA, SGLT2i, and TZD may be the most effective therapeutic methods for patients with NAFLD and T2DM.

Imaging Investigation of Hepatocellular Carcinoma Progress via Monitoring γ-Glutamyltranspeptidase Level with a Near-Infrared Fluorescence/Photoacoustic Bimodal Probe.

Hepatocellular carcinoma (HCC) is one of the main principal causes of cancer death, and the late definite diagnosis limits therapeutic approaches in time. The early diagnosis of HCC is essential, and the previous investigations on the biomarkers inferred that the γ-glutamyltranspeptidase (GGT) level could indicate the HCC process. Herein, a near-infrared fluorescence/photoacoustic (NIRF/PA) bimodal probe, CySO3-GGT, was developed for monitoring the GGT level and thus to image the HCC process. After the in-solution tests, the bimodal response was convinced. The various HCC processes were imaged by CySO3-GGT at the cellular level. Then, the CCl4-induced HCC (both induction and treatment) and the subcutaneous and orthotopic xenograft mice models were selected. All throughout the tests, CySO3-GGT achieved NIRF and PA bimodal imaging of the HCC process. In particular, CySO3-GGT could effectively realize 3D imaging of the HCC nodule by visualizing the boundary between the tumor and the normal tissue. The information here might offer significant guidance for the dynamic monitoring of HCC in the near future.

Abnormal liver function in children hospitalized with acute respiratory infection of adenoviruses: a retrospective study.

Human adenoviruses (HAdVs) can cause acute hepatitis in immunocompromised patients. However, it is unclear whether HAdVs are contributors to hepatitis in immunocompetent children. In this study, the liver function test (LFT) results were retrospectively analyzed among children hospitalized (age < 14 years) between January 2016 and October 2019 for acute respiratory infection caused by adenoviruses. Alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were elevated in 7.74% and 46.89% of patients, respectively. All patients with > 2 folds of the upper limit of ALT or AST levels were infected with HAdV-7 or HAdV-55. Significantly higher levels of ALT, AST, γ-glutamyl transpeptidase (γ-GT), and lower albumin levels were observed in the HAdV-7 infection group than in the HAdV-3 infection group. HAdV-55 infection led to significantly higher γ-GT, total bilirubin, and direct bilirubin levels than the other infection types. The records of four patients with serial monitoring of the LFT results were further analyzed. Multiple indicators remained abnormal during the entirehospitalization in these patients. These results indicate that HAdV infection is often accompanied by abnormal liver function, and HAdV-7 and HAdV-55 might be under-recognized contributors to hepatitis among children.

Abnormal liver function in children hospitalized with acute respiratory infection of adenoviruses: a retrospective study

Human adenoviruses (HAdVs) can cause acute hepatitis in immunocompromised patients. However, it is unclear whether HAdVs are contributors to hepatitis in immunocompetent children. In this study, the liver function test (LFT) results were retrospectively analyzed among children hospitalized (age <14 years) between January 2016 and October 2019 for acute respiratory infection caused by adenoviruses. Alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were elevated in 7.74% and 46.89% of patients, respectively. All patients with >2 folds of the upper limit of ALT or AST levels were infected with HAdV-7 or HAdV-55. Significantly higher levels of ALT, AST, γ-glutamyl transpeptidase (γ-GT), and lower albumin levels were observed in the HAdV-7 infection group than in the HAdV-3 infection group. HAdV-55 infection led to significantly higher γ-GT, total bilirubin, and direct bilirubin levels than the other infection types. The records of four patients with serial monitoring of the LFT results were further analyzed. Multiple indicators remained abnormal during the entire hospitalization in these patients. These results indicate that HAdV infection is often accompanied by abnormal liver function, and HAdV-7 and HAdV-55 might be under-recognized contributors to hepatitis among children.

Follicular cholangitis mimicking a common bile duct cancer: a case report

BackgroundFollicular cholangitis (FC) is a benign bile duct disease that was first reported 2003. Pathologically, it is characterized by lymphoplasmacytic infiltration with multiple lymphoid follicle formations under the mucosal layer of the biliary tract. However, as this disease is extremely rare, little is known about its etiology and pathogenesis.Case presentationA 77-year-old woman was diagnosed with middle bile duct stenosis and potential increases in alkaline phosphatase (ALP) and γ-glutamyl transpeptidase levels (γ-GTP). Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and IgG4 levels were all within the normal limits. Contrast-enhanced computed tomography (CE-CT) and magnetic resonance imaging (MRI) revealed bile duct dilation from intrahepatic to upper common bile duct and an irregular mass lesion in distal bile duct. Additionally, multiple overlapping leaf-like folds were detected. 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG-PET/CT) did not demonstrate fluorodeoxyglucose uptake. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed because common bile duct cancer could not be ruled out. The resected specimen showed diffuse homogeneous middle bile duct wall thickening. Microscopically, the lesion exhibited thick fibrosis with several invaded lymphoplasmacytic cells, and lymphoid follicle formations were detected under the mucosal layer. Immunohistochemical staining (IHC) revealed positive for CD3, CD4, CD20 and CD79a, and these findings led to a final diagnosis of FC. The patient has not experienced recurrence to date (42 months postoperatively).ConclusionsCurrently, accurate preoperative diagnosis of FC is difficult. More cases must be accumulated to generate additional knowledge on its precise diagnosis and proper treatment.

Effectiveness of One-Year Pemafibrate Therapy on Non-Alcoholic Fatty Liver Disease Refractory to Long-Term Sodium Glucose Cotransporter-2 Inhibitor Therapy: A Pilot Study.

Background: Both pemafibrate and sodium glucose cotransporter-2 (SGLT2) inhibitor can decrease serum transaminase levels in patients with non-alcoholic fatty liver disease (NAFLD) complicated with dyslipidemia and type 2 diabetes mellitus (T2DM), respectively. However, the effectiveness of combined therapy has been rarely reported. Methods: This is a two-center retrospective observational study. NAFLD patients complicated with T2DM treated with pemafibrate for >1 year were included, in whom prior treatment with SGLT2 inhibitor > 1 year failed to normalize serum alanine aminotransferase (ALT) levels. Hepatic inflammation, function, and fibrosis were assessed by ALT, albumin-bilirubin (ALBI) score, and Mac-2 binding protein glycosylation isomer (M2BPGi) levels, respectively. Results: Seven patients were included. The median duration of prior treatment with SGLT2 inhibitors was 2.3 years. During the one year before starting pemafibrate therapy, the therapy did not significantly change hepatic enzymes. All patients received pemafibrate 0.1 mg twice daily without dose escalations. During one year of pemafibrate therapy, triglyceride, aspartate aminotransferase, ALT, γ-glutamyl transpeptidase, ALBI score, and M2BPGi levels significantly improved (p < 0.05), although weight or hemoglobin A1c did not significantly change. Conclusions: One year of pemafibrate therapy improves markers of hepatic inflammation, function, and fibrosis in NAFLD patients in whom long-term SGLT2 inhibitor therapy failed to normalize serum ALT.

Imaging of a novel ratio γ-glutamyl transpeptidase fluorescent probe in living cells and biopsies

Herein, a novel fluorescent probe, GTP, was developed for monitoring the GGT (γ-glutamyl transpeptidase) level in living cells and biopsies. It consisted of the typical recognition group γ-Glu (γ-Glutamylcysteine) and the fluorophore (E)-4-(4-aminostyryl)-1-methylpyridin-1-ium iodide. With a ratio response between the signal intensity at 560 nm and 500 nm (RI560/I500), it could be important complement for the turn-on ones. With the linear range of 0–50 U/L, the limit of detection was calculated as 0.23 μM. The detection system showed the strongest response near pH 7.4, and exhibited steady fluorescence signals for at least 48 h. With high selectivity, good anti-interference and low cytotoxicity, GTP was suitable for physiological applications. By monitoring the GGT level with the ratio values in the green and blue channels, the probe GTP could distinguish cancer cells from normal cells. Furthermore, in the mouse tissues and humanization tissue samples, the probe GTP could also recognize the tumor tissues from the normal ones.