Evolving liver inflammation in biochemically normal individuals with anti-mitochondria antibodies

Abstract Background Anti-mitochondria autoantibodies (AMA) occur in > 95% primary biliary cholangitis (PBC) patients. Biochemically normal AMA-positive (BN/AMA+) individuals, occasionally noticed by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed in AMA-specific assays, may represent early stages of PBC. The Enhanced Liver Fibrosis (ELF) score is a surrogate marker for liver fibrosis. This prospective study investigated the ELF score in BN/AMA+ individuals and PBC patients, considering autoantibody avidity and serum levels along the years. Methods 327 samples from 35 PBC and 59 BN/AMA+ were prospectively obtained in average 3.83 (range 0.50–7.40) years apart. Samples were tested by IIF on rat-kidney (IIF-AMA), western-blot for AMA (WB-AMA), and ELISA for antibodies against pyruvate-dehydrogenase (PDC-E2), gp210, sp100 and CENP-A/B. Anti-PDC-E2 avidity was determined by 6 M urea-elution ELISA. Alkaline phosphatase (ALP), gamma glutamyl transferase (ɣGT) and ELF score were measured by automated methods. Results Along the follow-up period BN/AMA+ subjects and PBC patients presented significant increase in serum anti-PDC-E2 (mean 10.45% and 8.86% per year; respectively), anti-PDC-E2 avidity (3.02% and 4.94%/year) and ELF score (3.24% and 2.71%/year). IIF-AMA and ɣGT increased in BN/AMA+ (6.59% and 2.36%) and decreased in PBC (− 4.89%/year and − 3.88%/year). In BN/AMA+ individuals there was positive correlation of ELF with IIF-AMA titer (r = 0.465; p < 0.001) and with anti-PDC-E2 levels (r = 0.239; p < 0.001). Expansion of autoantibody targets along time occurred in 39% BN/AMA+ and 49% PBC patients. The frequency of BN/AMA+ with high probability of having established PBC increased from 7 to 14%. Conclusions BN/AMA+ individuals present an orchestrated increase in ELF score and humoral autoimmune response over time, indicating an opportunity for early therapeutic intervention and prevention in autoimmunity.

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Effect of nanopolysaccharide (BSEPS) from Bacillus subtilis sp. on thioacetamide-induced liver fibrosis in rats

Bulletin of the National Research Centre ◽

10.1186/s42269-019-0244-1 ◽

2019 ◽

Vol 43 (1) ◽

Author(s):

Manal G. Mahmoud ◽

Mohsen S. Asker ◽

Mohamed E. El Awady ◽

Amal I. Hassan ◽

Nadia A. R. Zaharan ◽

...

Keyword(s):

Bacillus Subtilis ◽

Liver Fibrosis ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Periodate Oxidation ◽

Hepatic Tissue ◽

Albino Rats ◽

Gamma Glutamyl Transferase ◽

Glutamyl Transferase ◽

Tgf Β1

Abstract Background Nanomedicine contributes to the efficiency of pharmacological treatments and progresses rapidly. The present study was designed to produce exopolysaccharide (BSEPS) from Bacillus subtilis sp. strain reported in our previous study was further characterized, and its BSEPS for synthesis of the nanoparticle Ag-BSEPS using microwave heating to determine the possible effects of a prepared solution containing Ag-BSEPS versus thioacetamide (TAA) evoked liver fibrosis in Wister albino rats. Nanoparticles with silver (Ag) core have been synthesized in an aqueous solution after exposure of BSEPS to periodate oxidation. Animals were split into four groups: I - control rats, water ad libitum for 6 weeks; II - rats were injected with TAA 200 mg/kg-1 3 times/week for 4 weeks IP; III - Ag-BSEPS 100 mg/kg-1 IP twice a week for 6 weeks; and IV - TAA, as group II followed by Ag-BSEPS as group III. The antifibrotic effects of Ag-BSEPS were appraised by determining different hepatotoxicity indices, oxidative stress, and inflammatory and liver fibrosis markers. Results Nanoparticles were obtained with a diameter size range of 50–100 nm characterized by SEM and TEM without using any harmful reagents. Results evinced considerably reduced activity of liver functions such as transaminases (AST, ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) in the group which received TAA followed by Ag-BSEPS compared to the other group which received only TAA. In the current results, the administration of Ag-BSEPS showed an improvement in the proinflammatory cytokines. On the contrary, the antioxidant enzymes in liver homogenates revealed significant improvement (concentration of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and catalase (CAT) increases) in animals with TAA-induced liver damage followed by Ag-BSEPS. Moreover, the activities of the fibrotic markers transforming growth factor-beta 1(TGF-β1) and type III pro-collagen (PCIII) were increased in liver tissues in the group which was given TAA alone as compared to the controls. The percentage of fibrosis of hepatic tissue had a positive correlation with the levels of PCIII and TGF-β1, followed by Ag-BSEPS compared to the TAA group without nanocomposite treatment. Microscopic examinations revealed inhibitory effects of Ag-BSEPS on inflammatory changes and deterrent of liver fibrosis. Conclusion It was suggested that the biochemical and histological amelioration observed in Ag-BSEPS (100 mg/kg-1 twice a week for 6 weeks) treated the fibrotic rats.

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Determinants of Change in Glycemic Status in Individuals with Prediabetes: Results from a Nationwide Cohort Study in Germany

Journal of Diabetes Research ◽

10.1155/2018/5703652 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Rebecca Paprott ◽

Christa Scheidt-Nave ◽

Christin Heidemann

Keyword(s):

Multinomial Logistic Regression ◽

Undiagnosed Diabetes ◽

Gamma Glutamyl Transferase ◽

Glycemic Status ◽

Prediabetic State ◽

Parental History ◽

Female Sex ◽

Glutamyl Transferase ◽

Diagnosed Diabetes

Previous studies investigating determinants of changes in glycemic status among individuals with prediabetes mainly focused on glucose-defined prediabetes. In this study, we examined determinants of a regression to normoglycemia or a progression to diabetes among individuals with HbA1c-defined prediabetes. The study included 817 participants (18–79 years) with prediabetes (HbA1c 5.7–6.4% (39–47 mmol/mol)) at baseline. Glycemic status at follow-up was categorized as diagnosed diabetes (self-reported physician diagnosis or antidiabetic medication), undiagnosed diabetes (HbA1c ≥ 6.5% (≥48 mmol/mol)), prediabetes (as defined at baseline), and normoglycemia (HbA1c < 5.7% (<39 mmol/mol)). Determinants of glycemic changes were identified by multinomial logistic regression (OR (95% CI)), with those remaining in the prediabetic state as reference. During a mean follow-up time of 12.0 years, 33.8% of the participants reverted to normoglycemia, 7.2% progressed to undiagnosed diabetes, 12.8% progressed to diagnosed diabetes, and 46.2% remained prediabetic. Determinants of a regression to normoglycemia were female sex (male vs. female: 0.67 (0.46; 0.98)) and higher HDL cholesterol levels (1.17 (1.02; 1.35) per 10 mg/dl). Determinants of a progression to undiagnosed or diagnosed diabetes were higher values of BMI (1.10 (1.02; 1.18); 1.13 (1.06; 1.21) per kg/m2), waist circumference (1.04 (1.01; 1.07); 1.06 (1.03; 1.09) per cm), alanine aminotransferase (1.06 (1.03; 1.09); 1.07 (1.03; 1.10) per U/l), and gamma-glutamyl transferase (1.02 (1.00; 1.03); 1.03 (1.01; 1.04) per U/l). Higher age (1.04 (1.02; 1.06) per year), female sex (male vs. female: 0.56 (0.33; 0.97)), and parental history of diabetes (yes vs. no: 1.82 (1.05; 3.15)) were further associated with a progression to diagnosed diabetes, whereas higher triglyceride levels (1.03 (1.01; 1.06) per 10 mg/dl) were associated with a progression to undiagnosed diabetes. In conclusion, among the investigated determinants, potentially modifiable anthropometric and metabolic markers were associated with glycemic changes in individuals with HbA1c-defined prediabetes. The findings of this study demonstrate the need for more refined case finding strategies for diabetes prevention.

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Relationship Between Serum Gamma-Glutamyl Transferase Level and Impaired Fasting Glucose Among Chinese Community-Dwelling Adults: A Follow-Up Observation of 6 Years

Metabolic Syndrome and Related Disorders ◽

10.1089/met.2020.0032 ◽

2020 ◽

Author(s):

Yun Wang ◽

Tingting Wu ◽

Xiu Zang ◽

Xuekui Liu ◽

Wei Xu ◽

...

Keyword(s):

Impaired Fasting Glucose ◽

Fasting Glucose ◽

Community Dwelling ◽

Gamma Glutamyl Transferase ◽

Chinese Community ◽

Gamma Glutamyl ◽

Glutamyl Transferase

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Serum Levels of Glutamate-Pyruvate Transaminase, Glutamate-Oxaloacetate Transaminase and Gamma-Glutamyl Transferase in 1494 Patients with Various Genotypes for the Alpha-1 Antitrypsin Gene

Journal of Clinical Medicine ◽

10.3390/jcm9123923 ◽

2020 ◽

Vol 9 (12) ◽

pp. 3923

Author(s):

José María Hernández Pérez ◽

Ignacio Blanco ◽

Agustín Jesús Sánchez Medina ◽

Laura Díaz Hernández ◽

José Antonio Pérez Pérez

Keyword(s):

Liver Damage ◽

Serum Levels ◽

Gamma Glutamyl Transferase ◽

Glutamate Oxaloacetate Transaminase ◽

Glutamate Pyruvate Transaminase ◽

Gamma Glutamyl ◽

Glutamate Pyruvate ◽

Alpha 1 Antitrypsin ◽

Glutamyl Transferase ◽

Normal Genotype

Background: Patients with liver disease associated with alpha-1 antitrypsin deficiency (AATD) are homozygous for the Z mutation, leading to chronic liver damage. Objective: To assess the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), and gamma-glutamyl transpeptidase (GGT) in patients with different genotypes for the alpha-1 antitrypsin (AAT) gene. Methods: Patients (n = 1494) underwent genotyping of the SERPINA1 gene, together with a determination of AAT and GOT and GPT and GGT transaminase levels. Patients with a deficient allele (n = 476) and with a normal genotype were compared. Results: A statistically significant association was found between deficient genotypes and GOT (p < 0.0003), GPT (p < 0.002), and GGT (p < 0.006). Comparing GOT levels in patients with PI*Z deficient variant versus those with normal genotype, an odds ratio (OR) of 2.72 (CI: 1.5–4.87) (p < 0.0005) was obtained. This finding was replicated with the PI*Z allele and the GPT values (OR = 2.31; CI: 1.45–3.67; p < 0.0003). In addition, a statistically significant association was found between liver enzymes and AAT values. Conclusion: The PI*Z allele seemed to be a risk factor for the development of liver damage. AAT deficient genotypes were associated with GOT, GPT, and GGT altered values. Low AAT levels were associated with high GPT and GGT levels.

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Lifetime duration of lactation and chronic inflammation among middle-aged women with a history of gestational diabetes

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001229 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001229

Author(s):

Sylvia H Ley ◽

Jorge E Chavarro ◽

Stefanie N Hinkle ◽

Mengying Li ◽

Michael Y Tsai ◽

...

Keyword(s):

Gestational Diabetes ◽

Chronic Inflammation ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Health Study ◽

Gamma Glutamyl Transferase ◽

Middle Aged ◽

History Of ◽

Glutamyl Transferase

IntroductionLonger duration of lactation is associated with lower cardiometabolic disease risk, but pathogenic pathways involved in the disease progression are unclear, especially among high-risk women. We aimed to examine the associations of lifetime lactation duration with cardiometabolic biomarkers among middle-aged women with a history of gestational diabetes (GDM).Research design and methodsWomen with a history of GDM participating in the Nurses’ Health Study II, a prospective cohort study, were identified and followed through biennial questionnaires beginning in 1991. Lactation history was asked in three follow-up questionnaires to calculate lifetime duration. In 2012–2014, fasting blood samples were collected through the Diabetes & Women’s Health Study to measure inflammatory (C-reactive protein (CRP), interleukin (IL) 6), liver enzyme (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase), and lipid biomarkers (total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol).ResultsAt follow-up blood collection, women were at median age 58.2 (95% CI 51 to 65) years and 26.3 (95% CI 15.7 to 34.1) years since GDM index pregnancy. After multiple adjustment including prepregnancy body mass index (BMI), longer duration of lactation was significantly associated with lower CRP (least squares (LS) mean 1.90 mg/L (95% CI 1.47 to 2.45) for 0-month lactation, 1.98 mg/L (95% CI 1.68 to 2.32) for up to 12-month lactation, 1.67 mg/L (95% CI 1.42 to 1.97) for 12–24 month lactation, and 1.39 mg/L (95% CI 1.19 to 1.62) for >24-month lactation; p trend=0.003) and IL-6 (1.25 pg/L (95% CI 0.94 to 1.68), 1.19 pg/L (95% CI 0.99 to 1.42), 1.04 pg/L (95% CI 0.87 to 1.25), and 0.93 pg/L (95% CI 0.78 to 1.11); p trend=0.04). Longer duration of lactation was associated with lower risk for chronic inflammation using CRP 3 mg/L cut-off in middle-aged women (OR 0.81 (95% CI 0.69 to 0.940 per 1-year increase) with multiple adjustment.ConclusionsLonger lifetime duration of lactation was associated with favorable inflammatory biomarker concentrations in middle-aged women with a history of GDM. Chronic inflammatory pathways may be responsible for previously reported associations between lactation and long-term risk for cardiometabolic diseases.

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Insufficient nocturnal sleep was associated with a higher risk of fibrosis in patients with diabetes with metabolic associated fatty liver disease

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018820947550 ◽

2020 ◽

Vol 11 ◽

pp. 204201882094755

Author(s):

Jiaping Zheng ◽

Sijie Chen ◽

Yuqing Cai ◽

Su Lin ◽

Sujie Ke ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Serum Uric Acid Level ◽

Multivariate Regression Analysis ◽

Gamma Glutamyl Transferase ◽

Baseline Characteristic ◽

Nocturnal Sleep ◽

Glutamyl Transferase

Background: Metabolic associated fatty liver disease (MAFLD) refers to metabolic dysfunction associated with fatty liver disease, and liver fibrosis stage is closely connected with liver-related and all-cause mortality. This study aimed to explore the association of sleep duration with liver fibrosis in the diabetic subgroup of the MAFLD population. Methods: This retrospective study analyzed 342 patients with MAFLD. Anthropometric measurements, clinical and biochemical markers, and lifestyle parameters were collected. Fibrosis was defined as fibrosis-4 ⩾1.3. Propensity score matching (PSM) was performed to match cases. Student’s t-test and chi-square tests were applied for group comparisons, and binary regression models were used to explore the independent risk factors of liver fibrosis. Results: Among the 342 subjects, 87 (25.4%) were diagnosed with fibrosis and 255 (74.6%) without. Baseline characteristic comparisons showed differences in age and diabetes duration between the two groups, and adjustment was made by PSM. Ultimately, the fibrosis group and nonfibrosis group each had 87 patients. The fibrosis group had shorter duration of nocturnal sleep (6.77 ± 1.59 h) than the nonfibrosis group (7.77 ± 1.92 h, p < 0.001). More patients in the fibrosis group stayed up late at night (32.2% versus 14.9%, p < 0.01). Visceral adipose tissue (VAT) areas were larger in the fibrosis group than in the nonfibrosis group ( p < 0.001). Glycemic profile, lipid profile, gamma-glutamyl transferase level, and serum uric acid level were not significantly different between the two groups. In the multivariate regression analysis, nocturnal sleep and VAT areas were independently associated with liver fibrosis, with odds ratios of 0.694 [95% confidence interval (CI) 0.551–0.875, p < 0.01] for nocturnal sleep and 1.031 (95% CI 1.014–1.048, p < 0.001) for VAT areas. Conclusion: Insufficient nocturnal sleep was independently related to a higher risk of fibrosis. Sleep modification might be beneficial in promoting the health of patients with MAFLD.

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Development of Radioimmunoassay for Gamma-Glutamyl Transferase Using Pancreatic Enzyme

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456328302000412 ◽

1983 ◽

Vol 20 (4) ◽

pp. 247-250 ◽

Cited By ~ 7

Author(s):

Masanobu Masuike ◽

Michio Ogawa ◽

Takeshi Kitahara ◽

Atsuo Murata ◽

Kazuhiko Matsuda ◽

...

Keyword(s):

Enzyme Assay ◽

Pancreatic Enzyme ◽

Gamma Glutamyl Transferase ◽

Gamma Glutamyl ◽

Standard Curve ◽

Normal Individuals ◽

The Mean ◽

Glutamyl Transferase ◽

Dilution Curves

A radioimmunoassay (RIA) for the determination of gamma-glutamyl transferase (GGT) was developed using human pancreatic enzyme as antigen. The assay allows the determination of GGT in concentrations as low as 80 ng/ml, and it is reproducible and specific. A good parallel relation was demonstrated between the standard curve and dilution curves for serum, urine, bile, and partially purified kidney GGT. In normal individuals, the mean serum concentration of GGT determined by RIA was found to be 3·43 μg/ml (SD ± 1·20). Enzyme activity calculated from the GGT concentration measured by the radioimmunoassay using a regression equation was approximately twice as great as that determined by conventional enzyme assay.

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(P2-63) An Evaluation of 57 Tick Bite Cases

Prehospital and Disaster Medicine ◽

10.1017/s1049023x11005073 ◽

2011 ◽

Vol 26 (S1) ◽

pp. s156-s156

Author(s):

M. Ortatatli ◽

R. Gumral ◽

H. Uckardes ◽

M. Eroglu ◽

L. Kenar ◽

...

Keyword(s):

Rural Areas ◽

Emergency Departments ◽

White Blood Cells ◽

Hemorrhagic Fever ◽

Health Staff ◽

Gamma Glutamyl Transferase ◽

Tick Bites ◽

Number Of Patients ◽

Glutamyl Transferase

Crimean-Congo Hemorrhagic Fever (CCHF) is a fatal zoonotic viral infection. The agent belongs to the Nairovirus of the Bunyaviridae species. The virus naturally recycles in vector-vertebrate-vector. This study aimed to evaluate cases of tick bites admitted to Infectious Diseases and Emergency Departments in 2008, and to develop management recommendations of such cases. Fifty-seven patients who admitted to a hospital due to tick bites in 2008 were included in the study. A 10-day clinical follow-up was performed to assess for symptoms including fever, fatigue, abdominal pain, headache, nausea/vomiting, diarrhea, disseminated somatic pain, and other hemorrhagic signs. During this period, laboratory analyzes, including white blood cells, thrombocytes, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, lactate dehydrogenase, creatinine phosphokinase (CK), and pentylenetetrazol were performed. Personal data of the patients, location of the bite, and the removal of the tick were recorded.ResultsOf the 57 patients, 37% were from the city, and 63% were from rural areas. The tick was removed by health staff in 25 (44%) of the cases. The bites occurred on body areas including the head/neck, trunk, upper extremities, and lower extremities in 14%, 24%, 27%, and 13% of the cases, respectively. During the follow-up period, none of the patients exhibited any of the signs or symptoms listed above. Laboratory tests did not reveal any abnormalities, except for high levels of CK in 15 patients. Thus, 57 cases did not develop CCHF.Discussion and ConclusionSince 2002, CCHF has caused an increased mortality in Turkey, and has resulted in high anxiety and concern among the Turkish public regarding tick bites. This has resulted in a rise in the number of patients admitting to emergency departments with tick bites. Due to CCHF's incubation period, patients with tick bites should be evaluated for 10 days using a multidisciplinary approach involving both clinical and laboratory evaluations in order to prevent the unnecessary administration of ribavirine.

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Sildenafil, a phosphodiesterase-5 inhibitor, offers protection against carbon tetrachloride-induced hepatotoxicity in rat

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2017-0011 ◽

2018 ◽

Vol 29 (1) ◽

pp. 29-35 ◽

Cited By ~ 4

Author(s):

Olorunfemi R. Molehin ◽

Anne A. Adeyanju ◽

Stephen A. Adefegha ◽

Oluwasanmi O. Aina ◽

Blessing A. Afolabi ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Density Lipoprotein ◽

Serum Levels ◽

Selective Inhibition ◽

Guanosine Monophosphate ◽

Control Group ◽

Gamma Glutamyl Transferase ◽

Protective Agent ◽

Glutamyl Transferase ◽

Phosphodiesterase 5

AbstractBackground:Elevation of phosphodiesterase-5 (PDE5) activity converts cyclic guanosine monophosphate (cGMP) to 5′-GMP, a mechanism that could be associated with drug-mediated hepatotoxicity. This study investigated whether selective inhibition of PDE5 by sildenafil could offer protection against hepatotoxicity induced by carbon tetrachloride (CCl4).Methods:CCl4(0.5 mL/kg) was administered intraperitoneally to induce hepatotoxicity. The control group received normal saline. Sildenafil (5 mg, 10 mg, and 20 mg/kg, p.o.) was administered to CCl4-treated rats.Results:CCl4significantly increased the serum levels of gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and reduced total protein (TP) (p<0.05). Pretreatment with sildenafil moderately reduced ALP, AST, and ALT activities with modest increase in TP level. CCl4-induced changes in the antioxidant status of the liver were significantly improved by sildenafil, especially at the lowest dose of 5 mg/kg by elevating the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) and preventing lipid peroxidation (p<0.05). Sildenafil did not significantly alter the total cholesterol and triglyceride levels. However, high-density lipoprotein (HDL) level was significantly increased by sildenafil (p<0.05).Conclusions:The results from this study suggest that sildenafil, when used at low doses, may be a useful pharmacological protective agent against CCl4-induced hepatotoxicity.

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