Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice

In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

Helicobacter pylori gamma-glutamyl transpeptidase and its pathogenic role

Helicobacter pylori(H.pylori)gamma-glutamyl transpeptidase(GGT)is a bacterial virulence factor that converts glutamine into glutamate and ammonia,and converts glutathione into glutamate and cysteinylglycine.H.pylori GGT causes glutamine and glutathione consumption in the host cells,ammonia production and reactive oxygen species generation.These products induce cell-cycle arrest,apoptosis,and necrosis in gastric epithelial cells.H.pylori GGT may also inhibit apoptosis and induce gastric epithelial cell proliferation through the induction of cyclooxygenase-2,epidermal growth factor-related peptides,inducible nitric oxide synthase and interleukin-8.H.pylori GGT induces immune tolerance through the inhibition of T cell-mediated immunity and dendritic cell differentiation.The effect of GGT on H.pylori colonization and gastric persistence are also discussed.

Serum Gamma-glutamyl Transferase Levels Predict Functional Outcomes after Aneurysmal Subarachnoid Hemorrhage

Objective We aim to explore the potential association between serum gamma-glutamyl transferase levels and functional outcome after aneurysmal subarachnoid hemorrhage in a Chinese population. Methods A total of 386 aneurysmal subarachnoid hemorrhage patients were included in the study from September 2007 to February 2015. Baseline serum gamma-glutamyl transferase levels and 6-month follow-up functional outcomes were determined. A poor outcome was defined as a modified ranking scale score of ≥ 3. The multivariable logistic model was used to analyze the relationship between serum gamma-glutamyl transferase and clinical outcomes after aneurysmal subarachnoid hemorrhage. Results The adjusted poor outcome rates of patients with gamma-glutamyl transferase levels of 〈 30 U/L, 30-50 U/L and ≥ 50 U/L were 16.7%, 19.6%, and 34.4%, respectively （P 〈 0.01）. The age-sex and multivariable adjusted odds ratios （95% confidence intervals） of poor prognosis comparing the top group （≥ 50 U/L） with the lowest group （〈 30 U/L） were 5.76 （2.74-12.13）, 6.64 （2.05-21.52）, and 6.36 （1.92-21.02）. A significant linear trend existed between gamma-glutamyl transferase level and aneurysmal subarachnoid hemorrhage prognosis. This association was also observed among nondrinkers. Conclusion Patients with higher gamma-glutamyl transferase levels were more likely to have a poor prognosis. Serum gamma-glutamyl transferase can be considered to be an independent predictor of functional outcomes after aneurysmal subarachnoid hemorrhage.

Association of serum gamma-glutamyl transferase with treatment outcome in chronic hepatitis B patients

AIM:To investigate the association of serum gammaglutamyl transferase(GGT) levels with chronic hepatitis B infection and hepatitis B e antigen(HBe Ag) seroconversion.METHODS:A retrospective study was performed on clinical data collected from patients who had been positive for hepatitis B surface antigen for > 6 mo and who were antiviral-treatment na?ve(n = 215) attending the Hepatitis Clinic at Nanjing Drum Tower Hospital between August 2010 and December 2013. Healthy individuals without liver disease(n = 83) were included as controls. Patients were categorized into four groups based on disease status as recommended by the European Association for the Study of the Liver:immune tolerance(IT; n = 47),HBe Ag-positive hepatitis(EPH; n = 93),HBe Ag-negative hepatitis(ENH;n = 20),and inactive carrier(IC; n = 55). Prediction of complete response(CR) based on serum GGT was also examined in EPH patients(n = 33) treated for 48 wk with nucleos(t)ide analogue(NA) therapy,including lamivudine plus adefovir combination therapy(n = 20) or entecavir monotherapy(n = 13). CR was defined as a serum hepatitis B virus DNA level < 500 copies/m L and HBe Ag seroconversion by 48 wk of treatment. RESULTS:Serum GGT levels were significantly increased in EPH and ENH patients relative to the IT,IC,and healthy control groups(P < 0.01 for all). However,no significant difference in serum GGT levels was found between the EPH and ENH groups. Baseline serum GGT levels were significantly higher in patients who achieved CR(7/33; 21.2%) compared to patients in the non-CR group(26/33; 78.8%; P = 0.011). In addition,the decline in serum GGT was greater in CR patients compared to non-CR patients after 24 wk and 48 wk of treatment(P = 0.012 and P = 0.008,respectively). The receiver operating characteristic curve yielded a sensitivity of 85.71% and a specificity of 61.54% at a threshold value of 0.89 times the upper limit of normal for baseline serum GGT in the prediction of CR following NA therapy. CONCLUSION:Serum GGT is significantly elevated in EPH and ENH patients and is a potential biomarker for the prediction of HBe Ag seroconversion following NA therapy.

Genetic Mutation of Vitamin K-dependent Gamma-glutamyl Carboxylase Domain in Patients with Calcium Oxalate Urolithiasis

To investigate the exon mutation of vitamin K-dependent gamma-glutamyl carboxylase （GGCX or VKDC） in patients with calcium oxalate urolithasis, renal cortex and peripheral blood samples were obtained from severe hydronephrosis patients （with or without calculi）, and renal tumor patients undergoing nephrectomy. GGCX mutations in all 15 exons were examined in 44 patients with calcium oxalate urolithiasis （COU） by polymerase chain reaction （PCR） and denatured high pressure liquid chromatography （DHPLC）, and confirmed by sequencing. Mutation was not found in all COU samples compared to the controls. These data demonstrated that functional GGCX mutations in all 15 exons do not occur in most COU patients. It was suggested that there may be no significant association between the low activity and mutation of GGCX in COU.

Effect of <i>Lactobacillus brevis</i>SBC8803 on Gamma-Glutamyl Transferase in Japanese Habitual Drinkers: A Double-Blind, Placebo-Controlled Study

A randomized, double-blind, placebo-controlled clinical trial in Japanese habitual drinkers was conducted to evaluate the efficacy of Lactobacillus brevis SBC8803 to alleviate adverse effect of alcohol. Subjects who drank habitually and had moderately higher levels of gamma-glutamyl transferase (GGT) (50 - 100 IU/L) were enrolled. The levels of transaminases in these subjects were almost within normal levels (aspartate transaminase (AST) <30 IU/L and alanine transaminase (ALT) <40 IU/L). Either the capsules containing placebo (n = 23) or 130 mg (4.0 × 1010 colony-forming units) of live L. brevis SBC8803 (n = 22) per day were administered for the continuous eight weeks (56 days). During the period, the subjects both in test group and placebo groups have kept each drinking behavior as usual. Regarding lipid metabolism, triacylglycerol (TG) levels in the male test group significantly decreased at week 4 as compared with week 0. Biomarkers of hepatocytes-damage;AST and ALT levels showed no significant differences between the pla- cebo and test groups at both weeks 4 and 8. Oxidative stress marker;GGT at weeks 4 was significantly lower in the test group than that in the placebo group (p = 0.017), but not at weeks 8. However, taking a reduced rate of GGT at weeks 8 comparing with that at week 0, that in the test group showed larger value comparing with that in the placebo group. These data about TG and GGT suggest that, although efficacy of L. brevis SBC8803 is limited in this study, intake of the probiotic may alleviate alcoholic influence in lipid metabolism and oxidative stress.

The Micro-determination of Serum Gamma-Glutamyl Transferase

The method of serum gamma-glutamyl transferase colorimeter assay was modified by changing the wave length from 420 nm to 400 nm, the incubated temperature from 37℃ to 50℃, the sample amount from 30 μl to 6μl. The modified method was proved to be more sensitive, with CV of intra-group being 2. 06% and accuracy 97. 4%. The method is suitable for clinical application with small-amount blood samples collected frorri earlobe or finger tip.

Prognostic utility of gamma-glutamyl transpeptidase to platelet ratio in patients with solitary hepatitis B virus-related hepatocellular carcinoma after hepatectomy

BACKGROUND The prognostic impact of preoperative gamma-glutamyl transpeptidase to platelet ratio(GPR)levels in patients with solitary hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)following radical resection has not been established.AIM To examine the clinical utility of GPR for prognosis prediction in solitary HBVrelated HCC patients.METHODS A total of 1167 solitary HBV-related HCC patients were retrospectively analyzed.GPR levels were compared with 908 non-HCC individuals.Overall survival(OS)and recurrence-free survival(RFS)were evaluated,and cox proportional hazard model analyses were performed to identify independent risk factors.Differences in characteristics were adjusted by propensity score matching(PSM).Subgroup and stratified survival analyses for HCC risks were performed,and a linear trend of the hazard ratio(HR)according to GPR levels was constructed.RESULTS GPR levels of patients with solitary HBV-related HCC were higher than those with hepatic hemangiomas,chronic hepatitis B and healthy control(adjusted P<0.05).Variable bias was diminished after the PSM balance test.The low GPR group had improved OS(P<0.001)and RFS(P<0.001)in the PSM analysis and when combined with other variables.Multivariate cox analyses suggested that low GPR levels were associated with a better OS(HR=0.5,95%CI:0.36-0.7,P<0.001)and RFS(HR=0.57,95%CI:0.44-0.73,P<0.001).This same trend was confirmed in subgroup analyses.Prognostic nomograms were constructed and the calibration curves showed that GPR had good survival prediction.Moreover,stratified survival analyses found that GPR>0.6 was associated with a worse OS and higher recurrence rate(P for trend<0.001).CONCLUSION Preoperative GPR can serve as a noninvasive indicator to predict the prognosis of patients with solitary HBVrelated HCC.

Gamma-glutamyl Transpeptidase to Platelet Ratio Predicts Liver Injury in Hepatitis B e Antigen-negative Chronic Hepatitis B Patients With Normal Alanine Aminotransferase

Background and Aims:Chronic hepatitis B virus(HBV)infection is a serious health problem worldwide.Evaluating liver injury in patients with hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)with detectable HBV DNA and normal alanine aminotransferase(ALT)is crucial to guide their clinical management.We aimed to investigate the stages of liver inflammation and fibrosis as well as the predictive accuracy of gamma-glutamyl transpepti-dase-to-platelet ratio(GPR)in these patients.Methods:A total of 184 treatment-naïve HBeAg-negative CHB pa-tients with detectable HBV DNA and normal ALT were enrolled.The Scheuer scoring system was used to classify liver inflammation and fibrosis.Results:The distribution of patients with different liver inflammation grades were as follows:G0,0(0%);G1,97(52.7%);G2,68(37.0%);G3,12(6.5%);and G4,7(3.8%).The distribution of patients with different liver fibrosis stages were as follows:S0,22(12.0%);S1,72(39.1%);S2,42(22.8%);S3,19(10.3%);and S4,29(15.8%).The areas under the re-ceiver operating characteristic(AUROC)curves of GPR in predicting significant inflammation,severe inflammation,and advanced inflammation were 0.723,0.895,and 0.952,respectively.The accuracy of GPR was significantly superior to that of ALT in predicting liver inflammation.The AUROCs of GPR in predicting significant fibrosis,severe fibrosis,and cirrhosis were 0.691,0.780,and 0.803,respectively.The predictive accuracy of GPR was significantly higher than that of aminotransferase-to-platelet ratio index(APRI)and fibrosis index based on four factors(FIB-4)in identifying advanced fibrosis and cirrhosis,and it was superior to FIB-4 but comparable to APRI in identifying significant fibrosis.Conclusions:Nearly half of the HBeAg-negative CHB patients with detectable HBV DNA and normal ALT levels had significant liver inflammation or fibrosis.GPR can serve as an accurate predictor of liver inflammation and fibrosis in these patients.

Serum Gamma-glutamyl Transferase Concentration Within the Reference Range is Related to the Coronary Heart Disease Risk Prediction in Korean Men： Analysis of the Korea National Health and Nutrition Examination Survey （V-1, 2010 and V-2, 2011）

Background：Limited data exist on the association of serum gamma-glutamyl transferase （GGT） level within the reference range with the increased risk of coronary heart disease （CHD） prediction in men.The study examined the association between serum GGT concentration within the reference range and the CHD risk prediction in Korean men.Methods：The study employed data from Korean National Health and Nutrition Examination Survey （V-1,2010 and V-2,2011） where a total of 1301 individuals were analyzed.A 10-year CHD risk prediction was computed using the Framingham Risk Score （FRS） modified by the National Cholesterol Education Program （NCEP） Adult Treatment Panel Ⅲ （ATP Ⅲ）.Results：Positive correlations were established between log-transformed GGT concentration and FRS （r =0.237,P 〈 0.001）.After adjustment of body mass index,the amount of alcohol intake and low-density lipoprotein-cholesterol,the odds ratio （95% confidence interval） for intermediate risk and beyond of 10-year CHD prediction （10-year risk ≥10%） with lowest quartile of participants was 1.21 （0.78-1.87） for second quartiles,1.39 （0.88-2.21） for third quartiles and 2.03 （1.23-3.34） for highest quartiles.Conclusions：Higher serum GGT within its reference range was significantly correlated with a 10-year CHD risk prediction estimation using NCEP ATP Ⅲ in Korean men.

The clinical implication of gamma-glutamyl transpeptidase in COVID-19

Background and aim:Coronavirus disease 2019(COVID-19)is a life-threatening disease that predomi-nantly causes respiratory failure.The impact of COVID-19 on other organs remains elusive.Herein,we aimed to investigate the effects of COVID-19 on the hepatobiliary system.Methods:In the current study,we obtained the clinical records and laboratory results from 66 laboratory-confirmed patients with COVID-19 at the Wuhan Tongji Hospital between 10 February 2020 and 28 February 2020.The detailed clinical features and laboratory findings were collected for analysis.Bioinformatics analysis was conducted to evaluate the correlation between gamma-glutamyl transferase(GGT)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry receptor angiotensin-converting enzyme 2(ACE2).Results:In this cohort,30(51.7%)patients had abnormal liver function on admission,which was asso-ciated with disease severity and enriched in the male and diabetic patients.The elevated levels of direct bilirubin(P¼0.029)and GGT(P¼0.004)were common in patients with severe pneumonia when compared with those with mild pneumonia.In addition,elevated levels of GGT(P¼0.003)and aspartate aminotransferase(AST)(P¼0.007)were positively associated with longer hospital stay.The expression of ACE2 was closely associated with GGT in various human tissues because they shared the common transcriptional regulator hepatic nuclear factor-1 b(HNF1B).Conclusions:Increased GGT levels were common in severe cases and elevated GGT levels were positively associated with prolonged hospital stay and disease severity.Due to the consistent expression with ACE2,GGT is a potent biomarker indicating the susceptibility of SARS-CoV-2 infection.

Gamma-glutamyl transferases： A structural, mechanistic and physiological perspective

Gamma glutamyl transferases （GGT） are highly conserved enzymes that occur from bacteria to humans. They remove terminal y-glutamyl residue from peptides and amides. GGTs play an important role in the homeostasis of glutathione （a major cellular antioxidant） and in the detoxification of xenobiotics in mammals. They are implicated in diseases like diabetes, inflammation, neurodegenerative diseases and cardiovascular diseases. The physiological role of GGTs in bacteria is still unclear. Nothing is known about the basis for the strong conservation of the enzyme across the living system. The review focuses on the enzyme＇s physiology, chemistry and structural properties of the enzyme with emphasis on the evolutionary relationships. The available data indicate that the members of the GGT family share common structural features but are functionally heterogenous.

γ-谷氨酰基化改善花生粕水解物的呈味效果及黄嘌呤氧化酶抑制作用研究

为提高花生粕的的加工利用价值,以黄嘌呤氧化酶抑制率和感官评价为指标,对花生粕酶解条件及γ-谷氨酰基化条件进行优化,同时分析酶解前后花生粕溶液的蛋白质及氨基酸含量变化,以确定花生粕蛋白的降解情况及γ-谷氨酰肽的合成情况。结果表明,pH 9.0,加酶量0.75%,温度55℃,酶解9 h为最佳酶解条件,黄嘌呤氧化酶抑制率可达(60.42±0.80)%。在谷氨酰胺酶添加量为4%,反应4 h下,对酶解产物进行γ-谷氨酰化修饰,其黄嘌呤氧化酶抑制率提高至(74.12±2.23)%(P<0.05),并能改善滋味特性。酶解前花生粕蛋白质分子质量主要集中在10~66 kDa,肽分子质量>10 kDa占比高达72.42%,经酶解后>10 kDa的蛋白质大幅度下降,5~10、3~5、1~3、<1 kDa都有明显增加(P<0.05)。酶解前总游离氨基酸为(11.38±0.78)mg/g,酶解后和γ-谷氨酰化后游离氨基酸含量分别为(88.82±2.80)、(74.86±7.49)mg/g,推测减少的氨基酸转化成了γ-谷氨酰肽。液相色谱-串联质谱联用分析发现γ-谷氨酰化后酶解液中生成了γ-Glu-Arg、γ-Glu-Leu、γ-Glu-Phe、γ-Glu-Met、γ-Glu-Tyr、γ-Glu-Val等肽段,产量约为25.98 mg/g,证明γ-谷氨酰化修饰可提高花生粕的黄嘌呤氧化酶抑制率,同时改善花生粕酶解物的滋味特性。研究结果为花生粕的再加工和产品开发提供理论依据。

肝功能相关指标联合胆囊收缩率在诊断胆道闭锁中的应用价值

目的探讨γ-谷氨酰转移酶(gamma-glutamyl transferase,GGT)、直接胆红素(direct bilirubin,DBil)与胆囊收缩率在诊断胆道闭锁(biliary atresia,BA)中的应用价值。方法收集2017年9月至2021年9月在西安交通大学附属儿童医院及西安市中心医院儿科住院治疗的185例胆汁淤积性肝病患儿为研究对象,根据剖腹探查或术中胆道造影和随访情况,将患儿分为BA组(70例)和肝内胆汁淤积(intrahepatic cholestasis,IHC)组(115例)。比较两组患儿的一般临床资料、实验室检查指标[包括总胆红素(total bilirubin,TBil)、DBil、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、GGT、碱性磷酸酶(alkaline phosphatase,ALP)、总胆汁酸(total bile acid,TBA)]及腹部超声检查资料。将有统计学意义的指标纳入受试者工作特征(receiver operator characteristic,ROC)曲线分析,计算ROC曲线下面积、最佳诊断界值和OR值;应用MedCalc软件进行ROC曲线下面积对比,分析各指标对诊断BA的价值。结果BA组和IHC组患儿的性别(男/女:31例/39例比78例/37例)、就诊年龄(中位数:52.0 d比58.0 d)、肝脏肋下大小(中位数:4.0 cm比2.0 cm)、脾大比例[40%(28/70)比18.3%(21/115)]、大便颜色、TBil(中位数:204.35μmol/L比138.30μmol/L)、DBil(中位数:125.70μmol/L比80.00μmol/L)、ALT(中位数:112.00 U/L比71.00 U/L)、AST(中位数:175.00 U/L比120.00 U/L)、GGT(中位数:440.75 U/L比94.50 U/L)、餐后1 h胆囊收缩率(无收缩/有收缩且<50%/有收缩且>50%:52.9%/41.4%/5.7%比7.0%/27.8%/65.2%)差异有统计学意义(P均<0.05)。两组患儿ALP(中位数526.00 U/L比548.00 U/L)、TBA(中位数:143.45μmol/L比161.90μmol/L)和25羟维生素D(中位数:8.00 ng/ml比8.13 ng/ml)水平差异无统计学意义(P均>0.05)。多因素Logistic回归分析表明,DBil(OR=1.031,95%CI:1.015~1.047,P<0.001)、GGT(OR=1.007,95%CI:1.004~1.011,P<0.001)、餐后1 h胆囊无收缩(OR=57.493,95%CI:9.577~345.133,P<0.001)和胆囊收缩率<50%(OR=9.907,95%CI:1.828~53.710,P=0.008)均为BA的危险因素。TBil、DBil、ALT、AST、GGT、GGT+DBil、GGT+DBil+胆囊收缩率诊断BA的ROC曲线下面积分别为0.797、0.820、0.614、0.658、0.890、0.932和0.963。单项指标中GGT的ROC曲线下面积最大,当GGT超过界值173.20 U/L时诊断BA的敏感度、特异度、阳性似然比、阴性似然比和诊断比值比分别为84.3%、78.3%、3.885、0.201和19.328。GGT+DBil+胆囊收缩率联合对BA的诊断价值最高,ROC曲线下面积显著高于GGT+DBil(z=2.303,P=0.021),其诊断BA的敏感度、特异度、阳性似然比、阴性似然比和诊断比值比分别为90.0%、90.4%、9.375、0.111和84.459。结论GGT、DBil与胆囊收缩率联合对BA有较高的诊断价值,当GGT超过界值173.20 U/L、DBil超过界值97.05μmol/L且超声提示胆囊收缩不良时需高度警惕BA。

血清镁离子浓度与直肠癌患者谷氨酰转肽酶的关系

直肠癌患者血清镁离子(Mg^(2+))浓度对γ-谷氨酰转肽酶(γ-GT)的影响尚不明确,收集分析临床数据,Mg^(2+)浓度不呈正态分布(D=0.737,P<0.05),按照中位数分组,比较不同组间临床病理特征的差异,用局部加权散点平滑(LOWESS)、分段线性回归方法,拟合血清Mg^(2+)浓度与γ-GT的关系。结果发现,与Mg^(2+)浓度小于0.92 mmol/L组的直肠癌患者比较,Mg^(2+)浓度≥0.92 mmol/L组的γ-GT和血清总胆固醇较高(P均<0.05)。LOWESS的结果表明,原始数据中血清Mg^(2+)浓度的两个变化点分别为0.92 mmol/L和0.99 mmol/L,自然对数转换的数据中血清Mg^(2+)浓度的另外两个变化点分别为-0.167和-0.01。利用原始数据建立的两段线性回归模型表明,血清Mg^(2+)浓度的变化点为0.98 mmol/L,Mg^(2+)浓度<0.98 mmol/L对γ-GT有正向影响,Mg^(2+)≥0.98 mmol/L时有负向影响。另一个使用自然对数转换数据的两段线性回归模型显示,血清Mg^(2+)浓度的变化点为0.01,其中Mg^(2+)浓度的自然对数<0.01对γ-GT有正向影响,当Mg^(2+)浓度的自然对数≥0.01时则有负向影响。用原始数据LOWESS回归的2个拐点,即0.92 mmol/L和0.99 mmol/L的Mg^(2+)浓度,进行三段线性回归分析,结果显示,<0.980 mmol/L的Mg^(2+)浓度,对γ-GT的影响是正向的,且与<0.929 mmol/L的Mg^(2+)浓度区间的系数不同,影响程度不同,而在≥0.980 mmol/L的Mg^(2+)浓度区间,对γ-GT的影响是负向的,此外,用对数转换数据LOWESS的2个拐点进行的三段线性回归,也显示Mg^(2+)浓度的自然对数以-0.020为分界点时,对γ-GT的影响方向是相反的,但三段线性回归模型均没有统计学意义,总之,具有较高Mg^(2+)浓度的直肠癌患者,其γ-GT的水平也较高,Mg^(2+)浓度对γ-GT的影响存在拐点效应,为γ-GT的关联因素研究提供了基础。

TBil、APRI联合GGT/Alb比值对胆道闭锁患儿肝纤维化严重程度的诊断价值

目的:探讨总胆红素(TBil)、天冬氨酸氨基转移酶/血小板比值指数(APRI)联合γ-谷氨酰转肽酶(GGT)/白蛋白(Alb)比值在诊断胆道闭锁(BA)患儿肝纤维化严重程度中的价值。方法:选取2021年9月至2023年9月于郑州大学附属儿童医院确诊且住院手术的BA患儿120例为研究对象,依据肝纤维化严重程度分为<F2期组和≥F2期组,记录患儿一般资料及临床指标。结果:≥F2期组患儿TBil、APRI、GGT/Alb比值、天冬氨酸氨基转移酶(AST)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-Col)、透明质酸(HA)、层黏蛋白(LN)显著高于<F2期组患儿(P<0.05)。BA患儿TBil、APRI、GGT/Alb比值与AST、PCⅢ、Ⅳ-Col、HA、LN均呈正相关(P<0.05)。TBil、APRI、GGT/Alb比值是BA患儿发生明显肝纤维化的独立危险因素(OR=2.939、2.873、2.895,P<0.05)。TBil、APRI、GGT/Alb比值单独及联合诊断的曲线下面积分别为0.837、0.841、0.851、0.956。结论:TBil、APRI、GGT/Alb比值联合在诊断BA患儿肝纤维化程度方面具有重要价值。

血清铁、CA19-9/GGT比值与肝细胞癌微血管侵犯、术后复发和预后的关系

目的:分析血清铁、癌胚抗原19-9(CA19-9)/γ-谷氨酰转肽酶(GGT)比值与肝细胞癌微血管侵犯(MVI)、术后复发和预后的关系。方法:选择2020年3月至2023年3月我院收治的80例肝细胞癌患者(肝癌组)和53例健康志愿者(对照组),根据是否发生MVI将患者分为MVI组(46例)和非MVI组(34例)。术前检测血清铁、CA19-9/GGT比值,术后定期随访,统计术后复发和总生存(OS)情况,根据复发情况分为复发组(26例)和非复发组(54例)。受试者工作特征(ROC)曲线分析血清铁和CA19-9/GGT诊断术前MVI的价值。分析血清铁、CA19-9/GGT比值与肝细胞癌MVI、术后复发和预后的关系。结果:肝癌组血清铁、CA19-9/GGT比值均高于对照组(P<0.05),肝内转移、TNM分期Ⅲ期、低度分化肝细胞癌患者血清铁、CA19-9/GGT比值高于无肝内转移、TNM分期Ⅰ~Ⅱ期、高中分化患者(P<0.05)。MVI组血清铁、CA19-9/GGT比值均高于非MVI组(P<0.05),复发组血清铁、CA19-9/GGT比值均高于非复发组(P<0.05)。血清铁和CA19-9/GGT诊断术前MVI的截断值分别为56.98μmol/L、2.53,曲线下面积为0.767、0.882,联合诊断为0.934,高于单独诊断(P<0.05)。血清铁高水平、CA19-9/GGT高比值肝细胞癌患者OS生存率低于血清铁低水平、CA19-9/GGT低比值患者(P<0.05)。TNM分期Ⅲ期、高血清铁水平、高CA19-9/GGT比值是肝细胞癌患者不良预后的危险因素(P<0.05)。结论:肝细胞癌患者血清铁水平和CA19-9/GGT比值增高,与术前MVI、术后复发和预后不良有关。

血清γ-谷氨酰转肽酶联合直接胆红素诊断婴儿胆道闭锁的价值

目的探讨血清γ-谷氨酰转肽酶(GGT)联合直接胆红素(DB)对胆道闭锁的诊断价值。方法选取2010年7月至2018年12月住院治疗的胆汁淤积症患儿667例为研究对象,根据术中胆管造影结果和随访情况,将患儿分为胆道闭锁组(n=234)和胆汁淤积组(n=433)。比较两组的发病年龄、性别,以及血清总胆红素(TB)、DB、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆汁酸(TBA)、GGT水平。将有统计学意义的指标纳入受试者工作特征曲线(ROC)分析,计算ROC曲线下面积(AUC)和最佳诊断界值。结果胆道闭锁组患儿发病年龄早于胆汁淤积组(P<0.001)。两组患儿性别、ALT及AST水平比较差异无统计学意义(P>0.05)。胆道闭锁组TB、DB、TBA、GGT水平显著高于胆汁淤积组(P<0.05)。GGT联合DB诊断胆道闭锁的AUC最大,为0.892(95%CI:0.868~0.916)。当GGT取值为324.0?U/L,DB取值为115.1?μmol/L时,GGT与DB联合诊断胆道闭锁的敏感度和特异度分别为79.8%、83.2%。结论 GGT联合DB诊断胆道闭锁的敏感度和特异度较高,可作为诊断胆道闭锁的有效指标之一。

GGT/PLT比值对广东地区慢性乙型肝炎患者肝纤维化分期的预测价值

目的探讨GGT/PLT比值(GPR)预测广东地区慢性乙型肝炎患者肝纤维化分期的价值。方法收集2010年1月-2016年12月于广州市第八人民医院行肝活组织检查诊断为慢性乙型肝炎的患者501例,其中HBe Ag阳性335例,HBe Ag阴性166例。分析比较GPR、GGT、AST/PLT指数(APRI)及FIB-4对肝纤维化分期(F1~F4)的预测价值。Spearman相关系数分析诊断模型指标与肝纤维化分期的相关性,采用受试者工作特征(ROC)曲线下面积评估各模型对肝纤维化分期的预测价值。结果肝活组织病理检查作为金标准,F1~F4期患者分别为141、183、139、38例。Spearman相关分析显示,HBe Ag阳性和HBe Ag阴性患者GGT、GPR、APRI和FIB-4均与肝纤维化分期呈正相关(r值分别为0.459、0.526、0.320、0.470、0.272、0.366、0.288、0.388,P值均<0.001),PLT与肝纤维化分期呈负相关(r值分别为-0.333、-0.349,P值均<0.001)。ROC曲线分析结果显示,GPR对于HBe Ag阳性慢性乙型肝炎患者明显肝纤维化(≥F2)、进展期肝纤维化(≥F3)及早期肝硬化(F4)的预测价值优于GGT和APRI(P值均<0.05),而与FIB-4的预测价值相近(P值均>0.05);GPR对于HBe Ag阴性慢性乙型肝炎患者明显肝纤维化(≥F2)的预测价值优于GGT和APRI(P值均<0.05),对进展期肝纤维化(≥F3)的预测价值优于GGT(P<0.05),而对早期肝硬化(F4)的预测价值与GGT、APRI、FIB-4相近(P值均>0.05)。结论 GPR可以作为广东地区慢性乙型肝炎患者肝纤维化分期的无创生化预测指标,尤其是对于HBe Ag阳性患者,其预测价值与FIB-4相近,亦不亚于APRI。