Serum Γ-glutamyltransferase Levels Research Articles

Biochemical and immunological investigation of fascioliasis in cattle in Egypt.

Background and Aim:Fasciola hepatica and Fasciola gigantica are two commonly reported liver flukes that cause fascioliasis in ruminants. Among the members of the genus Fasciola, F. hepatica was identified in the study area. Fascioliasis is a major disease that affects the production of livestock by causing liver damage. F. hepatica has developed advanced mechanisms to trick, elude, and alter the host immune response, similar to an extrinsic stressor. These mechanisms consequently affect the animals’ physiological and metabolic functions in vivo and postmortem changes, which have significant influences on animal welfare and meat quality development. Therefore, this study aimed to determine the current prevalence of cattle fascioliasis at abattoirs in El-Kharga city, New Valley Governorate, Egypt, and to investigate the changes in serum biochemical and immunological parameters and oxidative stress factors due to Fasciola spp. infection in terms of meat quality and immune response.Materials and Methods:A total of 226 cattle were inspected for the presence of Fasciola spp. The liver of each cattle was examined by making several incisions for detecting adult Fasciola spp. in El- Kharga. The blood samples were collected to analyze the changes in serum biochemical and immunological parameters and oxidative stress factors.Results:Of the 226 cattle, 38 (16.81%) were positive for F. hepatica at the postmortem examination. Cattle infected with F. hepatica had highly elevated serum alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, γ-glutamyl transferase, urea, and creatinine levels. Immunological cytokine profiles showed significantly increased serum interleukin (IL)-4, IL-10, and transforming growth factor-beta levels and a significantly decreased interferon-γ level. Furthermore, oxidative stress profiles showed significantly increased serum malondialdehyde and nitric oxide levels and significantly decreased total antioxidant capacity and reduced glutathione level.Conclusion:This study demonstrated that F. hepatica infection alone is an oxidative stress factor that affects slaughtered animals, leading to biochemical and metabolic alterations in the early postmortem period.

Association Between γ-Glutamyltransferase Level and Cardiovascular or All-Cause Mortality in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.

This meta-analysis assessed the prognostic value of serum γ-glutamyltransferase (GGT) level for cardiovascular (CV) and all-cause mortality in patients with coronary artery disease (CAD). We conducted a systematic literature search of PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang, and Weipu databases until December 2018. Observational studies investigating the prognostic role of serum GGT level for CV and all-cause mortality in patients with CAD were included. Pooled risk ratios (RR) with 95% confidence intervals (CI) for the highest versus the lowest GGT level were used to summarize the prognostic value. Twelve studies involving 12 531 patients with CAD were included. Meta-analysis showed that elevated GGT level was significantly associated with higher risk of CV mortality (RR: 2.04; 95% CI: 1.57-2.64) and all-cause mortality (RR: 1.49; 95% CI: 1.27-1.74) in patients with CAD. This meta-analysis suggests that elevated serum GGT levels are an independent predictor of CV and all-cause mortality in patients with CAD. Determination of GGT level may improve the prediction of CV and all-cause mortality in patients with CAD.

Moderate Serum γ-Glutamyl Transferase Level Is Beneficial for Heart Failure After Percutaneous Coronary Intervention.

Objective: Previous studies suggested that elevated serum γ-glutamyl transferase (GGT) level is an independent predictor of coronary artery disease (CAD) and heart failure (HF). However, whether serum GGT level has a predictive role for HF after percutaneous coronary intervention (PCI) remains unclear. This study aimed to evaluate the association of GGT with HF after PCI in a Chinese population. Methods: Five thousand six hundred thirty-eight patients were divided into three groups according to GGT tertiles: first tertile (GGT <19.6 U/L; n = 1875), second tertile (GGT ≥19.6-32.9 U/L; n = 1880), and third tertile (GGT ≥32.9 U/L; n = 1883). There were 165 (2.9%) HFs during a long-term follow-up. The average follow-up time was 35.9 ± 22.6 months. Results: The incidence of HF in the first tertile is 62 (3.3%), second tertile is 38 (2.0%), and third tertile is 65 (3.5%). The HF incidence was significantly lower in second tertile compared with that in the first tertile or in the third tertile (both P < 0.05). A U-shaped curve was observed according to quintiles (Q1:3.4%, Q2: 3.0, Q3:1.6%, Q4: 2.9%, Q5: 3.7%, P = 0.042). The multivariate Cox proportional hazards model showed after adjustment of confounders, the association remains significant (P = 0.046). Conclusions: This study indicated that serum GGT concentration was independently associated with HF after PCI. The baseline serum GGT level less than 19.6 or ≥32.9 increases HF risk in CAD patients who underwent PCI.

Clinical Characteristics and Prognostic Factors of Patients with Intrahepatic Cholangiocarcinoma with Fever: A Propensity Score Matching Analysis.

Patients with intrahepatic cholangiocarcinoma (ICC) rarely present fever as the initial symptom. We aimed to identify clinical characteristics and prognostic factors for these feverish patients. This study retrospectively reviewed 31 patients with ICC with fever (≥38.0°C) treated at our hospital between January 2002 and December 2014. A propensity score was used to match patients with and without fever at a ratio of 1:2. Patients with ICC with fever had higher serum γ-glutamyl transferase and carcinoembryonic antigen levels, larger tumors, poorer tumor differentiation, and worse prognosis (all p < .05) than those without fever. This was supported by propensity score matching (PSM) analysis. Univariate and multivariate analyses indicated that microvascular invasion, hilar lymph node metastasis, and temperature ≥ 38.6°C were related to prognosis. Patients with ICC with fever had higher levels of leucocytes, neutrophils, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in peripheral blood before and after PSM analysis. Body temperature positively correlated with leucocytes (r = 0.599, p < .001), neutrophils (r = 0.644, p < .001), NLR (r = 0.681, p < .001), and PLR (r = 0.457, p = .010). Patients with ICC with fever ≥38.0°C and ≥38.6°C had poor and extremely poor prognosis, respectively. Radical surgical treatment may improve the prognosis of patients with ICC with fever <38.6°C. However, systemic therapy (e.g., anti-inflammatory and immune therapy) may be preferable to surgery for these patients with fever ≥38.6°C. Patients with intrahepatic cholangiocarcinoma (ICC) with fever (≥38.0°C) as the initial symptom are extremely rare. Because their symptoms are similar to those of liver abscess, diagnosis is challenging, and most of these patients are already at an advanced stage at the time of diagnosis. Patients with ICC with fever had different clinical characteristics and worse prognosis than those without fever. The prognosis of those with temperature <38.6°C would be improved by timely surgical intervention. Those with fever ≥38.6°C had an extremely dismal outcome, although they all received radical surgical treatment. New therapeutic strategies are needed to improve survival for patients with ICC with temperature ≥38.6°C.

Effects of various interventions on the occurrence of macrovascular invasion of hepatocellular carcinoma after the baseline serum γ-glutamyltransferase stratification.

BackgroundElevated serum γ-glutamyltransferase (γ-GT) levels are related to an increased cancer risk and worse prognosis in many cancers. We evaluated the effects of γ-GT stratification on the occurrence of macrovascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) who underwent hepatic resection (HR), transcatheter arterial chemoembolization (TACE), or TACE combined with radiofrequency ablation (TACE-RFA).Patients and methodsA total of 903 patients with HCC in Barcelona Clinic Liver Cancer Stage A or B were included. Of these patients, 118 underwent HR, 445 underwent TACE-RFA, 256 underwent TACE, and 84 patients received conservative treatment only (control group). γ-GT, albumin, α-fetoprotein, and intervention were selected as significant predictive factors for MVI in 1 year by forward selection. The optimal cutoff value of γ-GT was 39 IU/L according to receiver operating characteristic analysis, with a sensitivity and specificity of 87.0% and 45.6%, respectively.ResultsThe 1-year MVI incidence of patients with HCC in the group with γ-GT ≥39 IU/L was higher than that of the group with γ-GT <39 IU/L treated with HR, TACE-RFA, or TACE (P=0.0166, P=0.0041, and P<0.001, respectively). The MVI rates at 1 year were similar in the group with γ-GT ≥39 IU/L that underwent HR, TACE-RFA, or TACE and the control group (P=0.4402, P=0.2214, and P=0.4159, respectively). Different effects of various treatments with γ-GT <39 IU/L group on the occurrence of MVI are not significant (P=0.5167). However, the incidence of MVI after TACE was significantly higher than that after HR or TACE-RFA in γ-GT ≥39 IU/L group (P=0.0253).ConclusionBaseline serum γ-GT stratification may help select the appropriate treatment to reduce the MVI incidence.

GW29-e0827 Serum γ-glutamyltransferase levels in predicting progression of coronary artery calcification in adults with type 2 diabetes

This study determine whether serum gamma- glutamyltransferase（GGT）levels can independently predict the progression of coronary artery calcification（CAC）in adults with type 2 diabetes. A total of 278 type 2 diabetic patients asymptomatic of cardiovascular disease were evaluated by CAC

Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism

To assess whether prolonged neonatal cholestasis, described in congenital hypopituitarism and septo-optic dysplasia (SOD), is associated with altered expression of selected canalicular ectoenzymes and canalicular transport proteins. Children with congenital hypopituitarism (n = 21), SOD (n = 18), and cholestasis seen in our center over 26 years were reviewed. Histopathologic findings in archival liver biopsy specimens were assessed (n = 10) and in those with low/normal levels of serum γ-glutamyltransferase (GGT) activity despite conjugated hyperbilirubinemia, expression of canalicular ectoenzymes and canalicular transport proteins was evaluated immunohistochemically. Patients presented at a median age of 8 weeks (range 3-20 weeks) with median total bilirubin 116 µmol/L (45-287 µmol/L), GGT 95 IU/L (25-707 UI/L), and serum cortisol 51 nmol/L (17-240 nmol/L). All but 3 had low free thyroxin (median 9.6 pmol/L [6.8-26.9]) with increased thyroid-stimulating hormone levels (median 5.95 mU/L [<0.1-9.24]). Liver histologic features included moderate-to-severe intralobular cholestasis with nonspecific hepatitis, giant-cell transformation of hepatocytes, and fibrosis. In all, immunohistochemical staining for canalicular ectoenzymes and canalicular transport proteins revealed a degree of reduced expression, associated with normal serum GGT values in 6 of the 10 patients, and another 6 nonbiopsied infants with cholestasis also had low/normal serum GGT activity. Sequencing of ABCB11 and ATP8B1 performed in 6 of the biopsied patients did not identify pathogenic mutations. Following replacement therapy, biochemical evidence of hepatobiliary injury resolved in all children within a median period of 6 months. Hepatobiliary involvement in congenital hypopituitarism associated with SOD has a good prognosis, but its etiology remains uncertain. Immunohistochemical expression of canalicular transport proteins was reduced in available liver samples.

The association between serum γ-glutamyl transferase and the dynamics of prealbumin/model for end stage live disease in patients with liver failure caused by hepatitis B virus

Objective To investigate the serum γ-glutamyl transferase (γ-GT) level and its clinical significances in hepatitis B virus (HBV)-liver failure (LF) patients. Methods γ-GT levels were detected in 89 LF patients, 30 cases with cirrhosis and 30 healthy controls. Difference of serum γ-GT between survival group and death group in LF patients and dynamics of γ-GT after hospitalization were studied. Survival rate between γ-GT increase group and decrease group were compared. The associations of γ-GT with model for end stage live disease (MELD) and prealbumin were calculated. Results At baseline, the γ-GT levels in LF, cirrhosis and healthy control groups were (149.61±69.86), (123.96 ±59.52) and (48.28±10.25) U/L, respectively, the difference among groups was significant (F=178.150, P<0.05). The survival group in LF patients showed significant increase of γ-GT one week after hospitalization compared with death group ([75.27±10.34] vs [29.47±5.05], t=5.40, P<0.05). The γ-GT increase group showed higher survival rate than γ-GT decrease group [76.19% (48/63) vs23.08% [6/26], χ2=21.76, P<0.05]. Serum γ-GT level in LF patients was positively correlated with both MELD score and prealbumin (r=0.709 and -0.627, respectively, both P<0.05). Conclusions The rise of γ-GT may indicate a better prognosis in LF patients. Serum γ-GT positively correlates with prealbumin and both could reflect the regeneration of hepatocytes. Key words: Liver failure; Prealbumin; γ-glutamyl transferase

Measurement uncertainty of γ-glutamyltransferase (GGT) in human serum by four approaches using different quality assessment data.

Measurement uncertainty (MU) characterizes the dispersion of the quantity values attributed to a measurand. Although this concept was introduced to medical laboratories some years ago, not all medical researchers are familiar with it. Therefore, the evaluation and expression of MU must be highlighted. In this paper, the evaluation of MU is described by using four different approaches from different quality assessment data. In accordance with Guide to the Expression of Uncertainty of Measurement (GUM) principles, human serum γ-glutamyltransferase (GGT) level was defined as the measurand. Main sources of MU were analyzed; individual components of MU were evaluated, followed by calculation of standard uncertainty, the combined standard uncertainty and the expanded uncertainty. In method 1, the median of expanded uncertainty (k=2) of GGT in lower level (65±1 U/L) was 5 U/L (9%, 95% confidence interval) and in higher level (116±2 U/L) was 8% (95% confidence interval), respectively. The results of method 2 were lower than that of method 1. There were no significant differences between the two other methods compared with the method 1. Three out of the four different approaches based on different quality assessment data yielded similar results. Proficiency testing or external quality assessment data used for MU evaluation can be regarded as a supplementary method in clinical laboratory.

Oxidative balance score and serum γ-glutamyltransferase level among Korean adults: a nationwide population-based study.

The oxidative balance score (OBS) comprises dietary and non-dietary lifestyle pro-oxidants and antioxidants. Elevated serum γ-glutamyltransferase (GGT) level has currently emerged as a biomarker of oxidative stress. In this study, we examined whether OBS was inversely associated with serum GGT level and whether OBS could be a useful marker to predict GGT among Korean adults. This cross-sectional study was based on data obtained from the 2010 and 2011 Korea National Health and Nutrition Examination Survey. 2087 men and 2071 women were included in final analysis. The OBS was divided into five equal interval categories, and GGT was dichotomized into low and high using its sex-specific median value. Multiple logistic regression analysis was conducted to assess the association between OBS categories and high GGT. Compared with the lowest OBS category as reference, the multivariable adjusted ORs (95% CIs) for the highest OBS category of men and women were 0.05 (0.01-0.19) and 0.27 (0.09-0.78), respectively (p for trend <0.01). A higher OBS that indicates a predominance of antioxidant over pro-oxidant exposure was strongly inversely associated with GGT level among Korean adults.

알코올로 유도된 간 손상 동물모델에서 굴 추출물의 간 보호 효과

This study was conducted to investigate the protective effects of water extract from Crassostrea gigas (CGW) against ethanol-induced hepatic toxicity in rats. Seventy-two male Wistar rats (6-week-old) were divided into six groups of 12 animals each: control group (1 mL saline/d), ethanol-treated group, positive control group (ethanol+Hovenia dulcis Thunb extract), CGWL group (ethanol+low dosage of CGW), CGWM group (ethanol+medium dosage of CGW), and CGWH group (ethanol+high dosage of CGW). All groups except the control group received ethanol (40% ethanol 5 g/kg) orally. CGW administration with ethanol resulted in prevention of ethanol-induced hepatotoxicity by increasing levels of serum alanine aminotransferase and γ-glutamyltransferase. CGW supplementation significantly reduced formation of malonaldehyde and inhibited reduction of hepatic glutathione and peroxidase levels, as compared with the ethanol-administration group. Further, CGW suppressed expression of CYP2E1, which was elevated by ethanol administration. Consequently, our results indicate that Crassostrea gigas may exert hepatoprotective effects against alcohol-induced hepatocyte injury by intensifying the anti-oxidative defense system.

The effects of tadalafil and pentoxifylline on apoptosis and nitric oxide synthase in liver ischemia/reperfusion injury

The aim of this study was to investigate the effects of tadalafil (TDF) and pentoxifylline (PTX) on hepatic apoptosis and the expressions of endothelial and inducible nitric oxide synthases (eNOS and iNOS) after liver ischemia/reperfusion (IR). Forty Wistar albino rats were randomly divided into five groups (n=8) as follows: sham group; IR group with ischemia/reperfusion alone; low-dose and high-dose TDF groups received 2.5 mg/kg and 10 mg/kg TDF, respectively; and PTX group received 40 mg/kg PTX. Blood was collected for the analysis of serum alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, uric acid, malondialdehyde (MDA), and total antioxidant capacity (TAC). MDA and TAC also were measured in liver tissue. Histopathological examination was performed to assess the severity of hepatic injury. Apoptosis was evaluated using the apoptosis protease-activating factor 1 (APAF-1) antibody; the expressions of eNOS and iNOS were also assessed by immunohistochemistry in all groups. Serum alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, uric acid, MDA, and TAC, tissue MDA and TAC levels, hepatic injury, and score for extent and for intensity of eNOS, iNOS, and apoptosis protease-activating factor 1 were significantly different in TDF and PTX groups compared to the IR group. High dose-TDF and PTX have the best protective effect on IR-induced liver tissue damage. This study showed that TDF and PTX supplementation may be helpful in preventing free oxygen radical damage, lipid peroxidation, hepatocyte necrosis, and apoptosis in liver IR injury and minimizing liver damage.

Nonalcoholic Fatty Liver Disease Is Associated With Ventricular Arrhythmias in Patients With Type 2 Diabetes Referred for Clinically Indicated 24-Hour Holter Monitoring.

Recent studies have suggested that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of heart rate-corrected QT interval prolongation and atrial fibrillation in patients with type 2 diabetes. Currently, no data exist regarding the relationship between NAFLD and ventricular arrhythmias in this patient population. We retrospectively analyzed the data of 330 outpatients with type 2 diabetes without preexisting atrial fibrillation, end-stage renal disease, or known liver diseases who had undergone 24-h Holter monitoring for clinical reasons between 2013 and 2015. Ventricular arrhythmias were defined as the presence of nonsustained ventricular tachycardia (VT), >30 premature ventricular complexes (PVCs) per hour, or both. NAFLD was diagnosed by ultrasonography. Compared with patients without NAFLD, those with NAFLD (n = 238, 72%) had a significantly higher prevalence of >30 PVCs/h (19.3% vs. 6.5%, P < 0.005), nonsustained VT (14.7% vs. 4.3%, P < 0.005), or both (27.3% vs. 9.8%, P < 0.001). NAFLD was associated with a 3.5-fold increased risk of ventricular arrhythmias (unadjusted odds ratio [OR] 3.47 [95% CI 1.65-7.30], P < 0.001). This association remained significant even after adjusting for age, sex, BMI, smoking, hypertension, ischemic heart disease, valvular heart disease, chronic kidney disease, chronic obstructive pulmonary disease, serum γ-glutamyltransferase levels, medication use, and left ventricular ejection fraction (adjusted OR 3.01 [95% CI 1.26-7.17], P = 0.013). This is the first observational study to show that NAFLD is independently associated with an increased risk of prevalent ventricular arrhythmias in patients with type 2 diabetes.

Serum γ-glutamyltransferase and Mortality due to Cardiovascular Disease in Japanese Men and Women.

Whether the association between serum γ-glutamyltransferase (γ-GTP) levels and total cardiovascular disease (CVD) mortality is independent of alcohol drinking in East Asian populations is not well known. We conducted a pooled analysis of Japanese men and women that enabled an analysis restricted to never-drinkers. A total of 15,987 men and 25,053 women aged 40-79 years, pooled from seven cohort studies throughout Japan, were followed-up to examine sex-specific relationship between serum γ-GTP levels and total CVD mortality. Cox regression model was used that was adjusted for age, smoking status, body mass index, and systolic blood pressure and serum triglyceride, total cholesterol, aspartate aminotransferase, and alanine aminotransferase levels. During an average follow-up of 8.7 years, we documented 361 and 340 deaths from total CVD, 146 and 168 from stroke, and 101 and 53 from coronary heart disease (CHD) for men and women, respectively. Among the never-drinkers, hazard ratios (HRs) for mortality for one standard deviation of log-γ-GTP for men were 1.89 (1.00-3.58) for stroke, 1.04 (0.57-1.90) for CHD, and 1.43 (1.04-1.96) for total CVD. For women, HRs were 1.28 (1.06-1.54), 1.81 (1.34-2.44), and 1.30 (1.14-1.49), respectively. γ-GTP may be a risk factor for total CVD mortality independent of alcohol drinking status in Japanese men and women.

Serum Mac-2 binding protein is a novel biomarker for chronic pancreatitis.

To determine the efficacy of Mac-2 binding protein (Mac-2bp) for diagnosis of chronic pancreatitis. Fifty-nine healthy volunteers (HV), 162 patients with chronic pancreatitis (CP), and 94 patients with pancreatic ductal adenocarcinoma (PDAC) were enrolled in this study. We measured serum Mac-2bp using our developed enzyme-linked immunosorbent assay kit. Additional biochemical variables were measured using an automated analyzer (including aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, triglyceride, C-reactive protein, and amylase levels) or chemiluminescent enzyme immunoassay (carbohydrate antigen 19-9 and carcinoembryonic antigen). The ability of Mac-2bp to predict CP diagnosis accurately was assessed using receiver operating characteristic (ROC) analyses. Serum Mac-2bp levels were significantly increased in CP patients compared to HV (P < 0.0001) and PDAC patients (P < 0.0001). Area under the ROC curve values of Mac-2bp for the discrimination of CP from HV and PDAC were 0.727 and 0.784, respectively. Multivariate analyses demonstrated that serum Mac-2bp levels were independent determinants for CP diagnosis from HV and PDAC patients. Immunohistological staining showed that Mac-2bp was expressed faintly in the pancreas tissues of both CP and PDAC patients. Serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, and triglyceride levels were significantly higher in patients with CP or PDAC. Serum Mac-2bp levels were highly correlated with protein levels of alanine aminotransferase, γ-glutamyltransferase, and C-reactive protein, but not amylase, suggesting that the damaged liver produces Mac-2bp. Measurement of serum Mac-2bp may be a novel and useful biomarker for CP diagnosis as well as liver fibrosis in the general population.

Analysis of mutations of MDR3 exons 9 and 23 in infants with parenteral nutrition-associated cholestasis.

The aim of this study was to investigate mutations of multidrug resistance 3 (MDR3) exons 9 and 23 in infants with parenteral nutrition-associated cholestasis (PNAC). A total of 41 infants with PNAC were enrolled in the study. Genomic DNA was extracted from the peripheral venous blood leukocytes of each patient and MDR3 exons 9 and 23 were amplified by polymerase chain reaction. One patient was identified who carried a frameshift mutation in MDR3 exon 23 (C.2793) that was caused by the insertion of a single adenine residue, while mutations were not found in MDR3 exon 23 in the other 40 patients. The clinical features of the patient with the MDR3 exon 23 frameshift mutation included high serum γ-glutamyl transferase levels, the absence of biliary dilatation and deformity in magnetic resonance cholangiopancreatography, and abnormal electrical capacitance tomography imaging of the liver. No mutations in MDR3 exon 9 were identified in any of the patients. All 41 PNAC patients recovered following oral ursodeoxycholic acid treatment. The C.2793 frameshift mutation in MDR3 exon 23 is potentially associated with the development of PNAC in infants.

Association between Plasma Endothelin-1, Transforming Growth Factor-β, Fibroblast Growth Factor, and Nitric Oxide Levels and Liver Injury in Hematopoietic Stem Cell Transplantation Recipients with Persistent Iron Overload after Transplantation

Graft-versus-host disease, iron overload, and infections are the major causes of liver dysfunction in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. We investigated the relationship between serum iron parameters and the levels of transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), endothelin-1 (ET-1), and nitric oxide (NO) as predictors of chronic liver injury in 54 AHSCT recipients who survived at least a year after transplantation. Serum samples from patients were obtained for the evaluation of ET-1, TGF-β, FGF, NO, and nontransferrin bound iron at the first year follow-up visit using commercially available ELISA kits. Patients were categorized depending on serum ferritin and transferrin saturation levels. The parameters were compared between the groups, and survival analysis was also performed. Most of the AHSCT recipients (81.5%) were in complete remission during the study. After a median follow-up time of 73 months (range, 13 to 109 months), 72.2% of the patients were alive. Mean serum levels of ET-1, NO, TGF-β, and FGF were 81.54 ± 21.62 μmol/mL, 31.82 ± 26.42 μmol/mL, 2.56 ± 0.77 ng/mL, and 50.31 ± 32.69 pg/mL, respectively. Nineteen patients (35.2% of the cohort) had serum ferritin levels higher than 1000 ng/mL. Mean serum levels of ET-1, NO, TGF-β, and FGF were similar in patients with serum ferritin levels below or above 1000 ng/mL (P > .05). Serum ferritin levels were positively correlated with serum alanine aminotransferase (r = .284, P = .042) and γ-glutamyl transferase (r = .271, P = .05) levels and were negatively correlated with serum albumin levels (r = .295, P = .034). There was a significant positive correlation between serum transferrin saturation and alanine aminotransferase levels (r = .305, P = .03). Serum ET-1 level was positively correlated with alkaline phosphatase levels (r = .304, P = .026). In univariate Cox regression analysis serum levels of iron parameters, ET-1, NO, TGF-β, and FGF did not have an impact on overall survival (P > .05). The probability of progression-free survival was also similar in patients with ferritin levels above or below 1000 ng/mL (P = .275). The probability of survival was similar in patients with transferrin saturation ≥70% and <70% (P > .05). Serum iron parameters showed a positive correlation with liver injury. However, there was no correlation between fibrogenic cytokines and liver transaminases. Our results suggest that iron overload at least with the current levels of ferritin might have a relatively benign course. Prospective randomized trials will guide the actual role of iron chelation in the post-transplantation setting.

Relationship between serum γ-glutamyltransferase level and leukocyte count in Korean children and adolescents

Background. Elevated γ-glutamyltransferase (GGT) is an important risk factor for cardiometabolic diseases, which may result from chronic low-grade inflammation. Leukocyte count is widely considered a marker of inflammation and is also an independent predictor of cardiometabolic diseases. This study aimed to determine the relationship between GGT and leukocyte count in a representative sample of Korean children and adolescents. Methods. A nationwide cross-sectional study was conducted to examine the relationship between GGT and leukocyte count in 830 boys and 714 girls (aged 10–18 years), using data from the 2010–2012 Korean National Health and Nutrition Examination Survey. The odds ratios (ORs) and 95% confidence intervals (CIs) for high leukocyte count (≥ 75th percentile) were calculated across GGT quartiles using multiple logistic regression analyses. Results. Leukocyte count gradually increased in accordance with serum GGT quartiles in both boys and girls (all p-values < 0.001). The OR (95% CI) for high leukocyte of the highest GGT quartile was 2.19 (1.05–4.58) for boys and 2.36 (1.13–4.93) for girls after adjusting for age, BMI, blood pressure, total cholesterol, triglyceride, physical activity, household income, and residential area. Similarly, these positive associations were observed in multiple logistic regression analysis using log2-transformed serum GGT as a continuous variable. Conclusions. The present study demonstrates a positive relationship between serum GGT and leukocyte count. These findings indicate that serum GGT may be closely related with subclinical low-grade inflammation in children and adolescents.

Increased levels of serum γ-glutamyltransferase and uric acid on metabolic, hepatic and kidney parameters in subjects at high altitudes.

Currently there are no studies on γ-glutamyltransferase (γGT) levels at high altitude or on the relationship between γGT, uric acid and several dysfunctions. The aim of the study was to determine the association between serum γGT and uric acid levels in subjects at high altitude with hemoglobin, glycemia, and lipidic, hepatic and kidney markers. The present study was performed in 487 subjects aged 30-75 years living at 4100 m of altitude. A venous blood sample was drawn from each subject to measure hemoglobin, glucose, and lipid levels and markers of liver and kidney function. Quartiles for serum γGT and uric acid were calculated and associated with different physiological variables. A p-value <0.05 was considered statistically significant. Serum γGT values were higher in men (38.35± 2.54 IU/L) than in women (30.33±1.76 IU/L) (p<0.01). Similarly, serum uric acid levels were higher in men (5.78± 0.12 mg/dL) than in women (4.29±0.08 mg/dL; p<0.001). Serum γGT levels in the top quartile were associated with higher glycemia, overweight/obesity, increased levels of non-high-density lipoprotein (non-HDL) cholesterol, triglycerides, alanine aminotransferase, alkaline phosphatase, uric acid, creatinine, and hemoglobin. Levels of uric acid in the top quartile were associated with overweight/obesity, elevated non-HDL cholesterol, triglycerides, creatinine, γGT and hemoglobin. Higher arterial blood pressure was associated with high levels of uric acid but not with γGT levels. At high altitude, increased γGT levels were associated with hyperglycemia; increased uric acid levels were associated with overweight/obesity, hemoglobin, dyslipidemia, high blood pressure and kidney disease.

Long-term native liver fibrosis in biliary atresia: Development of a novel scoring system using histology and standard liver tests

Although liver fibrosis is an important predictor of outcomes for biliary atresia (BA), postsurgical native liver histology has not been well reported. Here, we retrospectively evaluated postsurgical native liver histology, and developed and assessed a novel scoring system - the BA liver fibrosis (BALF) score for non-invasively predicting liver fibrosis grades. We identified 259 native liver specimens from 91 BA patients. Of these, 180 specimens, obtained from 62 patients aged ≥1 year at examination, were used to develop the BALF scoring system. The BALF score equation was determined according to the prediction of histological fibrosis grades by multivariate ordered logistic regression analysis. The diagnostic powers of the BALF score and several non-invasive markers were assessed by area under the receiver operating characteristic curve (AUROC) analyses. Natural logarithms of the serum total bilirubin, γ-glutamyltransferase, and albumin levels, and age were selected as significantly independent variables for the BALF score equation. The BALF score had a good diagnostic power (AUROCs=0.86-0.94, p<0.001) and good diagnostic accuracy (79.4-93.3%) for each fibrosis grade. The BALF score revealed a strong correlation with fibrosis grade (r=0.77, p<0.001), and was the preferable non-invasive marker for diagnosing fibrosis grades ⩾F2. In a serial liver histology subgroup analysis, 7/15 patients exhibited liver fibrosis improvement with BALF scores being equivalent to histological fibrosis grades of F0-1. In postsurgical BA patients aged ⩾1year, the BALF score is a potential non-invasive marker of native liver fibrosis.