Serum Gamma-glutamyl Transpeptidase Levels Research Articles

Comparison of different diagnostic methods in infants for differentiating idiopathic neonatal hepatitis from biliary atresia

Background: Biliary atresia (BA) and idiopathic neonatal hepatitis (INH) are two most common etiologies of neonatal cholestatic jaundice. It is important to distinguish INH from BA biliary atresia in an infant. The study was conducted to compare of different diagnostic methods in infants in differentiating INH and BA. Methods: This cross-sectional study was conducted at the Department of Pediatric Gastroenterology & Nutrition, BSMMU during the period from July 2018 to June 2019 among infants with neonatal cholestasis. Total 50 cholestatitic cases were selected through purposive sampling. A thorough history and physical examination were done and liver enzymes were studied. Abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy were done in all cases. Clinical parameter and investigational sensitivity, specificity, and diagnostic precision were calculated. To diagnose BA and INH, liver biopsy was considered the gold standard. Results: Among the participants, 72% were diagnosed as BA and 28% were INH. More than half of patients were male. There exists significant difference of birth weight and term baby between BA and INH. Presence of persistent pale coloured stool was more commonly seen in patients with BA. Diagnostic accuracy of persistent pale coloured stool, birth weight (normal) and term baby were 94%, 92% & 88% respectively. Sensitivity and specificity of Gammaglutamyl transpeptidase (GGT) in differentiating cases with BA and INH with cut point of ≥430.0 U/L were 86.1% and 85.7%, respectively. Hepatobiliary scintigraphy is found to have a better sensitivity than ultrasonography. GGT had diagnostic accuracy 86%, hepatobiliary scintigraphy had diagnostic accuracy 88% & USG had diagnostic accuracy 80% for BA and INH. Conclusion: Among the studied clinical parameters persistent pale coloured stool was most accurate to suggest the presence of BA. Serum level of GGT at cut-off value ≥ 430 U/L may be used as a reliable laboratory parameter to differentiate INH and BA. Hepatobiliary scintigraphy found to have a good sensitivity for BA. Positive result of hepatobiliary scintigraphy may be used as BA in infants with cholestasis. JOPSOM 2023; 42(1):14-20

Capecitabine enhances sensitivity to oxaliplatin in advanced gastric cancer and the effects on patients' FOXP1 and GGT levels

ObjectiveTo investigate the effect of capecitabine on the sensitivity of oxaliplatin and on the level of transcription factor forkhead box P1 (FOXP1) and gamma-glutamyl transpeptidase (GGT) in patients with intermediate and advanced gastric cancer. MethodsA total of 152 patients with intermediate and advanced gastric cancer diagnosed and treated in our hospital from April 2018 to May 2019 was selected as the research objects, and their clinical data were retrospectively analyzed. According to the different treatment methods, they were divided into the study group and the control group, with 76 cases in each group. The patients in the control group received with oxaliplatin, while the patients in the study group received with capecitabine on the basis of the control group. The therapeutic effect was evaluated according to the therapeutic effect evaluation criteria of solid tumors. The FOXP1 expression level in gastric cancer tissues was detected using immunohistochemistry. Serum levels of GGT were measured by chemiluminescence. The prognostic factors were analyzed by COX regression model, and the Kaplan-Meier survival curve was used to analyze the relationship between the influencing factors and the survival of gastric cancer. ResultsThe effective rate of capecitabine combined with oxaliplatin and oxaliplatin alone in the treatment of patients with intermediate and advanced gastric cancer were 94.74% and 76.32% respectively. Capecitabine enhanced the sensitivity of intermediate and advanced gastric cancer to oxaliplatin (P<0.05). Compared with adjacent normal tissues, the expression level of FOXP1 in gastric cancer tissues was lower (P<0.05). Before treatment, the expression of FOXP1 was low, and no significant difference was observed in the GGT level between the two groups (P>0.05). After treatment, the low expression rate of FOXP1 and serum GGT level were both significantly decreased, and those in the study group were lower than those in the control group (P<0.05). There was no difference in the incidence of adverse reactions between the two groups (P>0.05). The 1-year survival rates of the study group and the control group were 90.79% and 78.95%, while the 3-year survival rates of the study group and the control group were 75.00% and 51.32%, respectively. Both the 1-year and 3-year survival rate of the study group was higher than that in the control group (P<0.05). The 1-year survival rate of 152 patients with gastric cancer was 84.87% (129/152) and the 3-year survival rate was 63.17% (96/152). Age, tumor diameter, tumor-node-metastasis (TNM) stage, lymph node metastasis, chemotherapy regimen and the expression of FOXP1 and GGT had significant effects on the survival rate (P<0.05). Gastric cancer patients with age < 60 years, TNM stage of Ⅰ ∼ Ⅱ, lymph node metastasis N0 ∼ N1, high expression of FOXP1, GGT < 387.2, and combined with drug chemotherapy had higher survival rate. ConclusionCapecitabine effectively enhanced the sensitivity of intermediate and advanced gastric cancer to oxaliplatin, improved the therapeutic effect, reduced the proportion of patients with low FOXP1 expression rate and serum GGT level, decreased the recurrence rate and ameliorated the prognosis of patients.This is a retrospective study, all data were analyzed retrospectively. This research was approved by the Ethics Review Committees of Fuwai Central China Cardiovascular Hospital (approval number: 2023-EC-015).

Effect of Intermittent Fasting on Liver Function Tests: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Intermittent fasting (IF) is a diet strategy with alternate intervals of calorie reduction and normal eating. Despite its beneficial effects on weight loss and cardiometabolic risk factors, the effect of IF on liver function tests (LFTs) remains unclear. This study aimed to investigate the effect of IF on LFTs through a systematic review and meta-analysis of randomized clinical trials. An electronic search was performed using predefined search terms in databases including PubMed, Scopus, and ISI Web of Science until February 2023. The studies were selected according to PRISMA guidelines, and the risk of bias was assessed for the randomized controlled trials. The results of this study are reported as weighted mean differences (WMDs) with 95% CIs. Fourteen RCTs were included in the meta-analysis, with a total sample size of 908. IF significantly reduced alanine aminotransferase (ALT) (WMD: -2.88, 95% CI: -4.72 to -1.04, P-value = .002) and aspartate aminotransferase (AST) levels (WMD: -1.67, 95% CI: -3.12 to -0.22, P-value = .024). The results of the subgroup analysis showed that the impact of IF was significant in both the nonalcoholic fatty liver disease and the healthy groups for ALT. The effects of IF on the serum gamma-glutamyl transpeptidase (GGT) level were significant (WMD: -3.19, 95% CI: -6.00 to -0.39, P-value = .026), but there were no significant changes in the alkaline phosphatase (ALP) level (WMD: 1.06, 95% CI: -0.23 to 2.34, P-value = .106). Furthermore, no substantial heterogeneity between studies was reported. IF can improve ALT, AST, and GGT levels but not ALP enzyme levels and may have a benefit on liver function. PROSPERO registration no. CRD42023396211.

Differences in the prevalence of NAFLD, MAFLD, and MASLD according to changes in the nomenclature in a health check-up using MRI-derived proton density fat fraction.

International expert panels proposed new nomenclatures, metabolic dysfunction-associated fatty liver disease (MAFLD) in 2020 and metabolic dysfunction-associated steatotic liver disease (MASLD) in 2023, along with revised diagnostic criteria to replace non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the differences in NAFLD, MAFLD, and MASLD prevalence with changing nomenclature in a health check-up using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) to assess hepatic steatosis. We also examined the prevalence of the sub-classifications of steatotic liver disease (SLD) and the differences in characteristics among the sub-categories. We included 844 participants who underwent liver MRI-PDFF at our health check-up clinic between January 2020 and November 2022. Hepatic steatosis was defined as MRI-PDFF ≥ 5%. Participants were categorized according to NAFLD, MAFLD, MASLD, and sub-classifications of SLD. The prevalence rates of NAFLD, MAFLD, and MASLD were 25.9%, 29.5%, and 25.2%, respectively. 30.5% of the participants was categorized as SLD. The prevalence rates of the SLD sub-categories were 25.2% for MASLD, 3.7% for MASLD and alcohol-associated liver disease (MetALD), 0.1% for alcohol-associated liver disease, 1.3% for specific etiology SLD, and 0.1% for cryptogenic SLD. Compared with patients in the MASLD group, those in the MetALD group were younger, predominantly male, and exhibited higher levels of serum aspartate aminotransferase, gamma-glutamyl transpeptidase, and triglycerides. The prevalences of NAFLD and MASLD assessed using MRI-PDFF were similar, with MASLD accounting for 97.3% of the patients with NAFLD. The separate MetALD sub-category may have clinical characteristics that differ from those of MASLD.

Clinical Efficacy and Safety of Low-Dose Pemafibrate in Patients With Severe Renal Impairment: A Retrospective Study.

The management of hypertriglyceridemia in patients with chronic kidney disease (CKD) is important. Pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator with less toxic effects on liver and kidney function than those of other fibrates, has recently been approved for the treatment of patients with an estimated glomerular filtration rate (eGFR) lower than 30mL/min/1.73 m2. However, the efficacy and safety of pemafibrate in patients with severe renal impairment have not yet been established. This single-center, retrospective observational study included 12 outpatients with CKD and hypertriglyceridemia, who were newly started on low-dose pemafibrate (0.1 mg/day) treatment between December 2021 and May 2023 and whose eGFRs were less than 30 mL/min/1.73 m2 at baseline. Blood samples were collected before and at 12 weeks after pemafibrate treatment. After 12 weeks of treatment, the serum triglyceride level was significantly decreased, whereas the high-density lipoprotein cholesterol level was significantly increased. The serum alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and uric acid levels were also significantly decreased, without worsening of the eGFR and serum creatinine levels. In the subgroup analysis, there were no significant differences in the changes in clinical parameters regardless of statin use and CKD stage at baseline. Low-dose pemafibrate administration in patients with severe renal impairment resulted in significant improvements in triglyceride, high-density lipoprotein cholesterol, and serum uric acid levels, and liver function, without adverse events.

Esculeogenin A, a Glycan from Tomato, Alleviates Nonalcoholic Fatty Liver Disease in Rats through Hypolipidemic, Antioxidant, and Anti-Inflammatory Effects.

This study examined the preventative effects of esculeogenin A (ESGA), a newly discovered glycan from tomato, on liver damage and hepatic steatosis in high-fat-diet (HFD)-fed male rats. The animals were divided into six groups (each of eight rats): a control group fed a normal diet, control + ESGA (200 mg/kg), HFD, and HFD + ESAG in 3 doses (50, 100, and 200 mg/kg). Feeding and treatments were conducted for 12 weeks. Treatment with ESGA did not affect gains in the body or fat weight nor increases in fasting glucose, insulin, and HOMA-IR or serum levels of free fatty acids (FFAs), tumor-necrosis factor-α, and interleukin-6 (IL-6). On the contrary, it significantly reduced the serum levels of gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein cholesterol (LDL-c) in the HFD-fed rats. In addition, it improved the liver structure, attenuating the increase in fat vacuoles; reduced levels of TGs and CHOL, and the mRNA levels of SREBP1 and acetyl CoA carboxylase (ACC); and upregulated the mRNA levels of proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase I (CPT I) in HFD-fed rats. These effects were concomitant with increases in the mRNA, cytoplasmic, and nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO); a reduction in the nuclear activity of nuclear factor-kappa beta (NF-κB); and inhibition of the activity of nuclear factor kappa B kinase subunit beta (IKKβ). All of these effects were dose-dependent effects in which a normal liver structure and normal levels of all measured parameters were seen in HFD + ESGA (200 mg/kg)-treated rats. In conclusion, ESGA prevents NAFLD in HFD-fed rats by attenuating hyperlipidemia, hepatic steatosis, oxidative stress, and inflammation by acting locally on Nrf2, NF-κB, SREBP1, and PPARα transcription factors.

Gamma-glutamyl transpeptidase and indirect bilirubin may participate in systemic inflammation of patients with psoriatic arthritis

BackgroundPrevious studies have suggested that systemic metabolic abnormalities are closely related to psoriatic arthritis (PsA). Gamma-glutamyl transpeptidase (GGT) and indirect bilirubin (IBIL), two essential active substances in hepatic metabolism that have been demonstrated as an oxidative and anti-oxidative factor respectively, have been proved to be involved in oxidative stress damage and inflammation in several human diseases. However, their role in PsA remains unclear.MethodsIn this retrospective comparative cohort study, a case group of 68 PsA patients and a control group of 73 healthy volunteers from the Third Hospital of Hebei Medical University were enrolled. Serum GGT, IBIL, GGT/IBIL ratio and C-reactive protein (CRP), a well applied bio-marker of systemic inflammatory in PsA, were compared between the two groups. Furthermore, the relationship of GGT, IBIL and GGT/IBIL with CRP were explored in PsA patients. Finally, the patients were divided into high inflammation group and low inflammation group according to the median value of CRP. Multivariate logistic regression analyses were used for the association of systemic inflammation level with GGT, IBIL and GGT/IBIL.ResultsCompared with healthy controls, PsA patients exhibited significantly higher serum GGT, GGT/IBIL, and CRP levels and lower IBIL levels. Serum GGT and GGT/IBIL were positively correlated with CRP, whereas IBIL were negatively correlated with CRP. Binary logistic regression analysis revealed that serum GGT was a risk factor for high CRP in PsA, whereas IBIL was a protective factor. Furthermore, GGT/IBIL was a better indicator of high CRP condition in PsA patients than either GGT or IBIL alone, as determined by the receiver operating characteristic curves.ConclusionGGT and IBIL may participate in the pathogenesis of PsA. Additionally, GGT, IBIL and the balance of the two may reflect systemic inflammation mediated by oxidative stress events related to metabolic abnormalities to a certain extent.

Genetic polymorphisms of GGT1 gene (rs8135987, rs5751901 and rs2017869) are associated with neoadjuvant chemotherapy efficacy and toxicities in breast cancer patients

BackgroundOur previous study illustrated the predictive value of serum gamma-glutamyl transpeptidase (GGT) for neoadjuvant chemotherapy (NAC) sensitivity in breast cancer patients. In this study we aim to determine whether single nucleotide polymorphisms (SNPs) in the gamma-glutamyltransferase 1 (GGT1) gene are related to the NAC response and adverse events and to find out a genetic marker in predicting NAC sensitivity.MethodsThree SNP loci (rs8135987, rs5751901, rs2017869) of GGT1 gene were selected and tested among breast cancer patients reciving NAC. Four genotype models were used in SNP analysis: co-dominant model compared AA vs. Aa vs. aa; dominant model compared AA vs. Aa + aa; recessive model compared AA + Aa vs. aa; over-dominant model compared AA + aa vs. Aa. Chi-squared test and multivariable logistic regression analysis were performed between SNP genotypes, haplotypes and pathological complete response(pCR), adverse events as well as serum GGT level.ResultsA total of 143 patients were included in the study. For SNP rs8135987 (T > C), the TC genotype in over-dominant model was inversely related with pCR (adjusted OR = 0.30, 95% CI 0.10–0.88, p = 0.029) as well as the risk of peripheral neuropathy (adjusted OR = 0.39, 95% CI 0.15–0.96, p = 0.042). The TC genotype in dominant model was significantly associated with elevated serum GGT level (OR = 3.11, 95% CI 1.07–9.02, p = 0.036). For rs2017869 (G > C), the occurrence of grade 2 or greater neutropenia (OR = 0.39, 95% CI 0.08–0.84, p = 0.025) and leukopenia (OR = 0.24, 95% CI 0.08–0.78, p = 0.017) were both significantly reduced in patients with CC genotypes. For rs5751901(T > C), the CC genotype could significantly reduce the risk of grade 2 or greater neutropenia (OR = 0.29, 95% CI 0.09–0.96, p = 0.036) and leukopenia (OR = 0.27, 95% CI 0.09–0.84, p = 0.024) in recessive model.ConclusionsThe GGT1 gene SNPs might be an independent risk factor for poor response of NAC in breast cancer patients, providng theoretical basis for further precision therapy.

AN EXPERIMENTAL STUDY ON ALBINO RATS TO COMPARE THE HEPATOPROTECTIVE EFFECT OF ORALLY ADMINISTERED DL-METHIONINE AND N-ACETYLCYSTEINE ON THE LIVER INJURY CAUSED BY POSITIVE CONTROL DRUG DICLOFENAC SODIUM

Introduction: Liver, main organ for biotransformation of drugs, during which most of the drugs which are lipophilic in nature are made hydrophilic by the biochemical processes in the liver cells resulting into water-soluble products which get excreted in urine or bile. Adverse drug reactions (ADRs) pertaining to liver, can be of mainly two types, predictable or dose dependent and idiosyncratic. To counter the oxidative stress and cellular damage, several antioxidant enzymes have been developed including superoxide dismutase (SOD), Glutathione peroxidase and catalase, that detoxify the reactive oxygen species and the cells contained endogenous antioxidants that scavenge the free radicals and reduces the cellular damage of which glutathione plays a major role. Synthesis of glutathione is regulated at the substrate level by cysteine, which is synthesized from homocysteine via the trans-sulfuration pathway N-Acetylcysteine used as a specific drug in the treatment of Paracetamol overdose, serves as a prodrug to L-Cysteine, which is a precursor to the antioxidant Glutathione. L-methionine, a precursor of L-cysteine, which is considered to have antioxidant activity, is found to be a precursor to glutathione as well. Methionine is particularly important in opposing the toxicity of free radicals generated by various toxins. Hence, supplementation of the same has been proposed to have a greater role in reducing the toxic effect on liver. The aim was to study the comparative hepatoprotective effect of orally administered DL-Methionine and N-Acetylcysteine on the liver injury induced by positive control Diclofenac Sodium. Materials and Methods: The healthy albino rats were grouped for the experimental study, in various groups (n=6). After overnight fasting, rats belonging to Group I Vehicle treated Group (n=6) were administered Distilled Water 10 ml/kg orally Group II to V were administered single oral dose concomitantly with Diclofenac sodium (96 mg/kg &amp; 240 mg/kg p.o.) and DL-Methionine (700 mg/kg p.o. &amp; 1400 mg/kg p.o.) respectively. Group VI and VII were administered single oral dose concomitantly with Diclofenac sodium (96 mg/kg &amp; 240 mg/kg p.o.) and N-Acetylcysteine 450 mg/kg p.o., respectively. Serum samples from each rats were collected after 24-hours of post-treatment, to study the comparative effects of DL-Methionine and N-Acetylcysteine on the liver injury induced by positive control Diclofenac Sodium through Haemato-biochemical changes. Results: The vehicle-treated group showed no significant alteration in the level of liver function tests and liver morphology. On concomitant administration of DL-Methionine 700 mg/kg with Diclofenac sodium 96 mg/kg and 240 mg/kg it was observed that there occurred significant reduction (p &lt; 0.001) in the serum SGOT and SGPT levels as compared to control and positive control group. The hepatoprotective effect of DL-Methionine 700 mg/kg and N-Acetylcysteine 450 mg/kg on concomitant administration with positive control drug Diclofenac sodium 96 mg/kg were compared for their effect on serum SGPT levels and was observed that there was no statistically significant decrease in the levels of SGPT when compared between the two groups of hepatoprotective agents. The hepatoprotective effect of DL-Methionine 700 mg/kg and N-Acetylcysteine 450 mg/kg on concomitant administration with positive control drug Diclofenac sodium 240 mg/kg, were compared for their effect on serum SGPT levels. It was observed that there was a significant reduction (p &lt;0.05) in SGPT levels, with DL-Methionine 700 mg/kg and N-Acetylcysteine 450 mg/kg. However, in both the doses of DL-Methionine, there were no statistically significant changes in the Total Serum Bilirubin, serum Alkaline Phosphatase &amp; serum Gamma-Glutamyl Transpeptidase (GGTP) levels. Conclusion: We have compared for the effectiveness of DL-Methionine and N-Acetylcysteine for their hepatoprotective effect against Diclofenac-induced hepatotoxicity, where we have observed, both DL-Methionine and N-Acetylcysteine reduces the serum transaminases levels, that were elevated due to the hepatotoxic effect of diclofenac sodium. However, there was no much of a difference of hepatoprotective effect of both DL-Methionine and N-Acetylcysteine. In summary, our present study reinforced the concept that hepatotoxicity induced by drug can be protected by administering NAC even in cases of non-paracetamol induced liver injury.

T-cell infiltrate intensity is associated with delayed response to treatment in late acute cellular rejection in pediatric liver transplant recipients.

Late acute cellular rejection (ACR) is associated with donor-specific antibodies (DSA) development, chronic rejection, and allograft loss. However, accurate predictors of late ACR treatment response are lacking. ACR is primarily T-cell mediated, yet B cells and plasma cells (PC) also infiltrate the portal areas during late ACR. To test the hypothesis that the inflammatory milieu is associated with delayed response (DR) to rejection therapy, we performed a single-center retrospective case-control study of pediatric late liver ACR using multiparameter immunofluorescence for CD4, CD8, CD68, CD20, and CD138 to identify immune cell subpopulations. Pediatric liver transplant recipients transplanted at <17 years of age and treated for biopsy-proven late ACR between January 2014 and 2019 were stratified into rapid response (RR) and DR based on alanine aminotransferase (ALT) normalization within 30 days of diagnosis. All patients received IV methylprednisolone as an initial rejection treatment. Immunofluorescence was performed on archived formalin-fixed paraffin embedded (FFPE) liver biopsy tissue. Liver biopsies from 60 episodes of late ACR in 54 patients were included in the analysis, of which 33 were DR (55%). Anti-thymocyte globulin was only required in the DR group. The frequency of liver-infiltrating CD20+ and CD8+ lymphocytes and the prevalence of autoantibodies were higher in the DR group. In univariate logistic regression analysis, serum gamma-glutamyl transpeptidase (GGT) level at diagnosis, but not ALT, Banff score or presence of DSA, predicted DR. Higher serum GGT level, presence of autoantibodies, and increased CD8+ T-cell infiltration portends DR in late ACR treatment in children.

Ellagic acid from whole pomegranate fruit reduces liver injury in a rat model of hepatic cholestasis.

Cholestasis is a health problem, both in humans and animals, which in the disease's course involves oxidative stress, inflammation, and liver fibrosis. EA has been proven to have beneficial effects on various diseases. This study was conducted to determine the effect of EA in protecting liver damage because of cholestasis. In addition, to understand the underlying mechanism of liver damage in rats as a model animal by bile duct ligation (BDL) technique. In this study, male adult rats were used and randomly divided into three treatment groups. S is the sham-operated group, BDL is the group that is treated with BDL and the BDL-EA group is treated with BDL and given EA by gavage at a dose of 60 mg/kg bw/day, starting on the second day after BDL and given for 21 days. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT) were evaluated using spectrophotometer; tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β1) were evaluated using sandwich ELISA and histopathological examination using HE and Massion's Trichrome staining. In this study, BDL significantly increased serum levels of AST, ALT, ALP, and hepatic GGT. In addition, BDL also increased levels of TNF-α, and TGF-β1 compared to sham-operated controls. Histological studies in the BDL group also showed that the BDL increased the degree of necro-inflammation and collagen deposition area in the liver compared to the sham-operated group. Administration of EA has been shown to significantly improve liver morpho-function of the liver. I attenuated these changes in the BDL-EA group, where all observed study variables appeared to have improved. EA has been shown to reduce cholestasis that causes liver injury and improves liver enzyme profiles, and is suspected to have occurred because of its activities as an antioxidant, anti-inflammatory, and anti-fibrotic.

Circulating gamma-glutamyl transpeptidase and risk of pancreatic cancer: A prospective cohort study in the UK Biobank.

To determine whether serum gamma-glutamyl transpeptidase (GGT) level is associated with pancreatic cancer risk in a large prospective cohort. The study analyzed serum GGT concentration at baseline of 421,032 participants recruited in the UK Biobank since 2006 through 2010. Information on incidence of pancreatic cancer was obtained from cancer and death registers, updated until 2015 in Scotland or 2016 in England and Wales. Adjusted Cox proportional hazards models were used to measure the association between serum GGTand pancreatic cancer risk. The study identified 586 cases of pancreatic cancer over a median follow-up period of 7.16 years. In the multivariable-adjusted Cox model, serum GGT level was associated with 14% higher pancreatic cancer risk (hazard ratio (HR) per one standard deviation increment of log2 GGT level=1.14, 95% confidence interval (CI) 1.02-1.28, p= 0.025). In the total population, the HR for the highest GGT group was 1.68 (95%CI: 1.22-2.30) versus the lowest GGT group. The HR for the highest GGT group in men (≥50.2U/L) was 1.72 (95%CI: 1.14-2.61) and that in women (≥31.6U/L) was 1.75 (95%CI: 1.06-2.88) versus the lowest GGT group. Our findings suggested a positive association of serum GGT in pancreatic cancer etiology, implying the potential of monitoring GGT level for identifying at-risk individuals for pancreatic cancer.

Clinical and genetic characterization of pediatric patients with progressive familial intrahepatic cholestasis type 3 (PFIC3): identification of 14 novel ABCB4 variants and review of the literatures

BackgroundProgressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disease caused by pathogenic variants of the gene ABCB4. This study aimed to investigate the ABCB4 genotypic and the clinical phenotypic features of PFIC3 patients.MethodsThe clinical and molecular genetic data of 13 new pediatric patients with PFIC3 as well as 82 reported ones in the PubMed and CNKI databases were collected and analyzed.ResultsThe 13 new PFIC3 patients included six females and seven males, and the main presentations were hepatomegaly, splenomegaly, jaundice, and pruritus, as well as increased levels of gamma-glutamyl transpeptidase (GGT). Fourteen new ABCB4 variants were detected, including eight diagnosed to be likely-pathogenic and six, pathogenic. Among all the 95 PFIC3 cases, hepatomegaly was observed in 85.3% (81/95), pruritus in 67.4% (64/95), splenomegaly in 52.6% (50/95), jaundice in 48.4% (46/95), portal hypertension in 34.7% (33/95) and GGT elevation in 100% (88/88) of the patients. Positive responses at varied degrees to oral ursodeoxycholic acid (UDCA) treatment were observed in 66.1% (39/59) of the patients, among whom 38.5% (15/39) fully recovered in terms of the laboratory changes. Although the condition remained stable in 53 patients (58.9%, 53/90), the clinical outcomes were not promising in the rest 37 cases (41.1%, 37/90), including 7 died, 27 having undergone while another 3 waiting for liver transplantation. A total of 96 ABCB4 variants were detected in the 95 patients. PFIC3 patients with biallelic null variants exhibited earlier onset ages [10.5 (2, 18) vs. 19 (8, 60) months, p = 0.007], lower UDCA response rate [18.2% (2/11) vs. 77.1% (37/48), p = 0.001], and more unpromising clinical outcomes [80% (12/15) vs. 33.3% (25/75), p = 0.001], compared with those with non-biallelic null variants.ConclusionsPFIC3 presented with hepatomegaly, pruritus, splenomegaly and jaundice with increased serum GGT level as a biochemistry hallmark. Although varying degrees of improvement in response to UDCA therapy were observed, 41.1% of PFIC3 patients exhibited unfavorable prognosis. ABCB4 genotypes of biallelic null variants were associated with severer PFIC3 phenotypes. Moreover, the 14 novel variants in this study expanded the ABCB4 mutation spectrum, and provided novel molecular biomarkers for diagnosis of PFIC3 patients.

ODP323 Increased Serum High-Sensitivity C-Reactive Protein Levels in Adult Growth Hormone Deficient Patients with Non-Functioning Pituitary Tumors

Abstract Background Growth hormone (GH) deficiency, a common endocrine deficit in non-functioning pituitary tumors, causes visceral obesity and fatty liver and increases cardiovascular event risks. High-sensitivity C-reactive protein (hs-CRP) has been used as a useful marker to estimate cardiovascular event risks. Because GH supplementation therapy was reported to decrease serum hs-CRP levels in GH deficient patients, inflammatory processes might be activated in GH deficient state, however, the underlying mechanism has been still unknown. Patients and Methods We retrospectively reviewed charts of 134 patients with non-functioning pituitary adenoma and Rathke's cysts who underwent preoperative GH-releasing peptide-2 (GHRP-2) tests and investigated the association between serum hs-CRP levels and background characteristics. Patients who had a history of pituitary surgery, severe renal insufficiency or active inflammatory diseases or received GH supplementation therapy were excluded. GH secretion was determined by GHRP-2 tests. Results Among 134 patients (94 NFPA and 40 Rathke's cysts), 46 (34%) presented severe GH deficiency, as diagnosed using GHRP-2 tests. Serum hs-CRP levels were significantly higher in the patients with severe GH deficiency than in those without severe GH deficiency (723 [299-1285] vs 278 [124-561] ng/mL, P &amp;lt; 0. 001). Serum hs-CRP levels were significantly higher in men (P = 0. 003) and in patients with diabetes mellitus (P = 0. 040) and were significantly correlated with age (r s = 0.19, P = 0. 039), body mass index (r s = 0.37, P &amp;lt; 0. 001), serum levels ofgamma-glutamyl transpeptidase(r s = 0.28, P = 0. 001), creatinine (r s = 0.30, P &amp;lt; 0. 001), low-density lipoprotein cholesterol (r s = 0.21, P = 0. 013), triglyceride (r s = 0.38, P &amp;lt; 0. 001) and free thyroxine (r s = -0.30, P= 0. 001), blood hemoglobin A1c levels (r s = 0.20, P = 0. 018), peak GH response to GHRP-2 (r s = -0.47, P &amp;lt; 0. 001) and IGF-1 SD score (r s = -0.18, P = 0. 040). In the multiple regression analysis, peak GH response to GHRP-2 was a significant variable for determining serum hs-CRP levels (β = -0.340, P = 0. 003) after adjustment with age, sex, BMI, smoking, alcohol consumption, hypertension, diabetes mellitus, serum levels ofgamma-glutamyl transpeptidase, creatinine,triglyceride and free thyroxine and adrenal function. Conclusion We observed a significant association between GH deficiency and increased serum hs-CRP levels independent to BMI and liver dysfunction. GH deficient state might cause inflammation independent to development of visceral obesity and fatty liver. Presentation: No date and time listed

The health effects of low blood lead level in oxidative stress as a marker, serum gamma-glutamyl transpeptidase level, in male steelworkers.

This study aimed to investigate the association between lead exposure and serum gamma-glutamyl transpeptidase (γGT) levels as an oxidative stress marker in male steelworkers. Data were collected during the annual health examination of workers in 2020. A total of 1,654 steelworkers were selected, and the variables for adjustment included the workers' general characteristics, lifestyle, and occupational characteristics. The association between the blood lead level (BLL) and serum γGT level was investigated by multiple linear and logistic regression analyses. The BLL and serum γGT values that were transformed into natural logarithms were used in multiple linear regression analysis, and the tertile of BLL was used in logistic regression analysis. The geometric mean of the participants' BLLs and serum γGT level was 1.36 μg/dL and 27.72 IU/L, respectively. Their BLLs differed depending on age, body mass index (BMI), smoking status, drinking status, shift work, and working period, while their serum γGT levels differed depending on age, BMI, smoking status, drinking status, physical activity, and working period. In multiple linear regression analysis, the difference in models 1, 2, and 3 was significant, obtaining 0.326, 0.176, and 0.172 (all: p < 0.001), respectively. In the multiple linear regression analysis stratified according to drinking status, BMI, and age, BLLs were positively associated with serum γGT levels. Regarding the logistic regression analysis, the odds ratio of the third BLL tertile in models 1, 2, and 3 (for having an elevated serum γGT level within the first tertile reference) was 2.74, 1.83, and 1.81, respectively. BLL was positively associated with serum γGT levels in male steelworkers even at low lead concentrations (< 5 μg/dL).

Hematological, Biochemical, and Skeletal Muscle Metabolic Responses to Exercise Related Myopathy in Endurance Horses

Equine exertional rhabdomyolysis (ER) is a well-recognized disease affecting racehorses therefore this study was performed to evaluate haemato-biochemical alterations in 20 adult Arabian horses after 120 km race with trial of treatment. Horses were classified into 2 main groups: the first group (n:5) included healthy control horses while the second group(n:15) included horses showed signs of distress, moderately depressed, muscle stiffness, shifting hind limb lameness, elevated respiratory rate, sweating, firm painful hindquarter muscles, myoglobinuria and reluctance to move that lasts for several hours after ending of race. Based on the history and the through clinical examination of diseased horses, they were tentatively diagnosed as suffering from ER syndrome. Whole blood and serum samples were collected from both healthy control horses and diseased ones before and after treatment. Hemogram of examined horses showed only significant increased PCV (%) values of diseased horses with more prominent thrombocytopenia but with treatment their values showed marked improvement, where other haematological parameters showed non-significant changes in both groups either before or after treatment. Serum analysis of ER affected horses showed a higher serum enzymatic activities of creatine phosphokinase (CK) and aspartate aminotransferase (AST) with significantly increased values of total proteins, albumin, globulins, total bilirubin, glucose, creatinine and potassium. But with effective treatment protocol, these higher values began to be improved towards normal values again. While non-significant changes were observed in serum levels of Gamma-glutamyl transpeptidase (GGT), calcium, sodium and blood urea nitrogen (BUN) in ER affected horses. Based on obtained results, ER has negative impact on haemato-biochemical biomarkers with remarkable serum elevation of skeletal muscular specific enzymes, as well as by paralytic myoglobinuria.

Increased Uric Acid, Gamma-Glutamyl Transpeptidase and Alkaline Phosphatase in Early-Pregnancy Associated With the Development of Gestational Hypertension and Preeclampsia.

Background: Previous studies have reported that biomarkers of liver injury and renal dysfunction were associated with hypertensive disorders of pregnancy (HDP). However, the associations of these biomarkers in early pregnancy with the risk of HDP and longitudinal blood pressure pattern during pregnancy were rarely investigated in prospective cohort studies.Methods: A total of 1,041 pregnant women were enrolled in this prospective cohort study. BP was assessed in four stages throughout pregnancy. The following biomarkers were measured at early pregnancy before 18 weeks gestation: lactate dehydrogenase (LDH), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), uric acid (UA), and estimated glomerular filtration rate (eGFR). Linear mixed-effects and logistic regression models were used to examine the associations of these biomarkers with longitudinal BP pattern during pregnancy and HDP incidence, respectively.Results: In unadjusted models, higher serum UA, GGT, ALP, and LDH levels, as well as lower eGFR and AST/ALT, were associated with higher BP levels during pregnancy and an increased risk of HDP. After adjustment for maternal age, pre-pregnancy BMI and other potential confounders, UA, GGT, ALP, and LDH remained positively associated with both BP and HDP. However, eGFR and AST/ALT were not associated with HDP after adjusting for potential confounders. When including all 6 biomarkers simultaneously in multivariable analyses, increased UA, GGT, and ALP significantly associated with gestational hypertension and preeclampsia.Conclusion: This study suggests that increased UA, GGT, and ALP in early-pregnancy are independent risk factors of gestational hypertension and preeclampsia.

Cirrhotic Liver of Liver Transplant Recipients Accumulate Silver and Co-Accumulate Copper

Silver-based materials are widely used in clinical medicine. Furthermore, the usage of silver containing materials and devices is widely recommended and clinically approved. The impact on human health of the increasing use of silver nanoparticles in medical devices remains understudied, even though Ag-containing dressings are known to release silver into the bloodstream. In this study, we detected a widespread and sometimes significant silver accumulation both in healthy and sick liver biopsies, levels being statistically higher in patients with various hepatic pathologies. 28 healthy and 44 cirrhotic liver samples were investigated. The median amount of 0.049 ppm Ag in livers was measured in cirrhotic livers while the median was 0.0016 ppm for healthy livers (a more than 30-fold difference). The mean tissue concentrations of essential metals, Fe and Zn in cirrhotic livers did not differ substantially from healthy livers, while Cu was positively correlated with Ag. The serum levels of gamma-glutamyl transpeptidase (GGTP) was also positively correlated with Ag in cirrhotic livers. The increased Ag accumulation in cirrhotic livers could be a side effect of wide application of silver in clinical settings. As recent studies indicated a significant toxicity of silver nanoparticles for human cells, the above observation could be of high importance for the public health.

Upgraded nomograms for the prediction of complications and survival in patients with colorectal liver metastases treated with neoadjuvant chemotherapy followed by hepatic resection.

BackgroundTo establish upgraded nomograms incorporating neoadjuvant chemotherapy (NAC)-related factors and preoperative testing markers to predict postoperative complications, progression-free survival (PFS) and overall survival (OS) in patients with colorectal liver metastases (CRLM).MethodsMultivariate regression analyses were used to reveal independent predictors for postoperative complications, PFS and OS. Nomograms incorporating independent predictors were constructed, and discrimination and calibration were evaluated. Survival was estimated by the Kaplan-Meier method and compared using the log-rank test.ResultsA nomogram predicting postoperative complications was constructed based on preoperative serum gamma-glutamyl transpeptidase (GGT) ≥36 U/L, major liver resection, intraoperative blood loss ≥300 mL, primary site located in the right hemicolon and primary lymph node metastasis, with an area under the receiver operating characteristic curve (AUROC) of 0.750. The calibration curves and Hosmer-Lemeshow test revealed desirable model calibration (chi-square: 4.47, P=0.88). Moreover, a nomogram for the prediction of PFS was constructed based on tumour regression grade (TRG), primary lymph node metastasis, R0 resection and NAC cycles ≥5, with good discrimination (C-index: 0.663±0.024) and calibration, and one for predicting OS was constructed based on preoperative GGT ≥36 U/L, NAC toxicity, NAC cycles ≥5, primary lymph node metastasis and R0 resection, with favourable discrimination (C-index: 0.684±0.030) and calibration. Significant differences in PFS and OS were observed among patients stratified into three different risk groups (P<0.001) according to total scores based on the nomograms.ConclusionsThis study is the first to establish novel predictive nomograms specifically incorporating TRG, NAC toxicity and serum GGT level for the prediction of postoperative complications, PFS and OS in CRLM patients. The nomograms exhibit favourable discrimination and calibration to guide personalized CRLM management and therapy.

Serum levels of gamma-glutamyl transpeptidase in relation to HCC human biology and prognosis.

Background and aim:Hepatocellular carcinoma (HCC) biomarkers are limited, as even the best studied, alpha-fetoprotein (AFP), is elevated in no more than 50% of HCC patients. The aim was to evaluate several serum liver function tests in relation to survival and tumor characteristics in a large cohort of Turkish HCC patients.Methods:We retrospectively examined the serum levels of gamma glutamyl transpeptidase (GGT) in relation to patient survival.Results:Kaplan-Meier analysis showed that only GGT and albumin amongst liver function tests, were significantly associated with survival. Survival worsened with increase in GGT levels semi-quantitatively. Increase in GGT levels was also found to significantly correlate with an increase in maximum tumor diameter from 4.5 to 7 cm, a 20-fold increase in serum alpha-fetoprotein level, an increase in tumor multifocality from 20 to 54% of patients, and a doubling in percent of patients with portal vein thrombosis (PVT) from 20 to 40%. Serum GGT levels also showed significant survival differences for patients with low AFP levels. A doublet combination of serum GGT with albumin levels was associated with higher hazard ratios in a Cox regression analysis, as compared with single parameter GGT. The combination parameter pair was also prognostically useful in the low-AFP patient subcohort and was associated with significant differences in patient tumor characteristics.Conclusions:Serum GGT levels and especially combination serum GGT plus albumin levels, were significantly associated both with HCC patient survival and tumor aggressiveness characteristics, regardless of AFP levels in a large Turkish cohort. This might be especially useful since the majority of HCC patients do not have elevated levels of AFP.