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Declining diagnostic accuracy of non-invasive fibrosis tests is associated with elevated alanine aminotransferase in chronic hepatitis B

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World Journal of Clinical Cases 2018年第12期6卷 521-530页

作者： Lin Wang Yao-Xin Fan Xiao-Guang Dou Department of Infectious Diseases Shengjing Hospital of China Medical Uni-versity

AIM To explore the effect of alanine aminotransferase(ALT) on the performance of non-invasive fibrosis tests in chronic hepatitis B(CHB) patients. METHODS A total of 599 treatment-naive and biopsy-proven CHB patients were included in the study. The cohort was divided into the following three groups: Normal ALT(ALT ≤ 40), slightly elevated ALT(40 80). The diagnostic performance of five common non-invasive fibrosis tests for liver fibrosis(stages S2-4), including the aspartate aminotransferase(AST)-to-platelet(PLT) ratio index(APRI), fibrosis index based on 4 factors(FIB-4), King's score, Forns index and gamma-glutamyl transpeptidase(GGT)-to-PLT ratio(GPR), were evaluated for each group. RESULTS Higher ALT levels were associated with higher non-invasive fibrosis test scores. Patients with the same fibrosis stage but higher ALT levels showed higher noninvasive test scores. The areas under the receiver operating characteristics curves(AUROCs) of the noninvasive tests for prediction of ≥ S2 were higher for patients with ALT ≤ 40 U/L(range 0.705-0.755) and 40 80 U/L(range 0.604-0.701). The AUROCs for predicting ≥ S3 and S4 were higher in patients with ALT ≤ 40 U/L(range 0.736-0.814 for ≥ S3, 0.79-0.833 for S4) than in patients with 40 80 U/L(range 0.7-0.784 for ≥ S3, range 0.662-0.719 for S4). The diagnostic accuracy of the non-invasive tests decreased in a stepwise manner with the increase in *** ALT has a significant effect on the diagnostic performance of non-invasive fibrosis tests. The ALT level should be considered before performing these noninvasive tests.

关键词： Chronic hepatitis B Non-invasive tests Liver fibrosis Alanine aminotransferase Inflammation

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Validation of aspartate aminotransferase to platelet ratiofor diagnosis of liver fibrosis and prediction of postoperativeprognosis in infants with biliary atresia

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World Journal of Gastroenterology 2015年第19期21卷 5893-5900页

作者： LiYuan Yang Jie Fu XiaoFang Peng ShuYin Pang KanKan Gao ZhengRong Chen LiJuan He Zhe Wen Hui Wang Le Li FengHua Wang JiaKang Yu Yi Xu SiTang Gong HuiMin Xia HaiYing Liu Li-Yuan Yang Xiao-Fang Peng Shu-Yin Pang Kan-Kan Gao Hai-Ying Liu Clinical Laboratory Guangzhou Medical University Affiliated Guangzhou Women and Children's Medical Center Guangzhou 510120 Guangdong Province China.

Validation of aspartate aminotransferase to platelet ratiofor diagnosis of liver fibrosis and prediction of postoperativeprognosis in infants with biliary atresia pathological Metavir fibrosis score of the liver wedgespecimens of 91 BA infants. The prognostic value ofpreoperative APRI for jaundice persistence, liver injury,and occurrence of cholangitis within 6 mo after KP wasstudied based on the follow-up data of 48 BA ***： APRI was significantly correlated withMetavir scores （rs = 0.433; P 〈 0.05）. The mean APRIvalue was 0.76 in no/mild fibrosis group （Metavir scoreF0-F1）, 1.29 in significant fibrosis group （F2-F3）, and2.51 in cirrhosis group （F4）（P 〈 0.001）. The areaunder the ROC curve （AUC） of APRI for diagnosingsignificant fibrosis and cirrhosis was 0.75 （P 〈 0.001）and 0.81 （P = 0.001）, respectively. The APRI cut-offof 0.95 was 60.6% sensitive and 76.0% specific forsignificant fibrosis diagnosis, and a threshold of 1.66was 70.6% sensitive and 82.7% specific for *** preoperative APRI in infants who maintainedjaundice around 6 mo after KP was higher than thatin those who did not （1.86 ± 2.13 vs 0.87 ± 0.48, P 〈0.05）. The AUC of APRI for prediction of postoperativejaundice occurrence was 0.67. A cut-off value of0.60 showed a sensitivity of 66.7% and a specificityof 83.3% for the prediction of jaundice *** APRI had no significant association withlater liver injury or occurrence of ***： Our study demonstrated that APRIcould diagnose significant liver fibrosis, especiallycirrhosis in BA infants, and the elevated preoperativeAPRI predicts jaundice persistence after KP.

关键词： Aspartate aminotransferase to platelet ratioindex Biliary atresia Cirrhosis Liver fibrosis Prognosis

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Determination of the upper cut-off values of serum alanine aminotransferase and aspartate aminotransferase in Chinese

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World Journal of Gastroenterology 2015年第8期21卷 2419-2424页

作者： Peng Zhang Chun-Yan Wang Yu-Xiang Li Yu Pan Jun-Qi Niu Shu-Mei He Department of Infectious Disease the First Hospital of Jilin University University of Oklahoma Health Science Center Department of Hepatopathy the First Hospital of Jilin University The First Hospital of Jilin University

AIM:To determine the upper cut-off values of serumalanine aminotransferase(ALT)and aspartate aminotransferase(AST)in a Northern Chinese ***:A total of 3769 subjects in Jilin Province Northeast China were stratified to determine the potential factors affecting serum ALT and AST *** upper cut-off values of serum ALT and AST in these subjects were determined using receiver operating characteristic analysis and their sensitivity and specificity were ***:Stratification analysis revealed that serum ALT and AST levels were associated with gender,alcohol consumption,serum cholesterol and triglyceride levels,and body mass *** upper cut-off values of serum ALT and AST were 22.15 U/L and 25.35 U/L for healthy men and 22.40 U/L and 24.25 U/L for healthy women,*** new cut-off values had a higher sensitivity,but a slightly lower specificity than the current ***:Our results indicate that the new upper cut-off values of serum ALT and AST are markedly lower than current standards and may be valuable for the evaluation of liver function.

关键词： Alanine aminotransferase Aspartate aminotransferas

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Alanine aminotransferase normalization at week 8 predicts viral response during hepatitis C treatment

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World Journal of Gastroenterology 2013年第46期19卷 8678-8686页

作者： Umit Bilge Dogan Mustafa Salih Akin Serkan Yalaki Departments of Gastroenterology Adana Numune Training and Research Hospital

AIM:To investigate alanine aminotransferase(ALT)and sustained virological response(SVR)in chronic hepatitis C(CHC)during peginterferon-ribavirin ***:One hundred and fifty-one genotype 1CHC patients underwent treatment for 48 wk with peginterferon and ribavirin,and were retrospectively divided into two groups as having a rapid virological response(RVR)(Group 1,n=52)and not having an RVR(Group 2,n=99).We also subdivided each group into two according to the initial ALT level being high(Group1h and Group 2h)or normal(Group 1n and Group 2n).HCV RNA and ALT levels were measured at baseline;at 4,12,24 and 48 wk during the treatment period;and at 24 wk *** levels were also obtained at 8 *** to the results of ALT,patients were enrolled in either the follow-up abnormal or follow-up normalized ALT groups at each *** with high and normal ALT levels were compared for each interval in terms of ***:The SVR rates were 83%vs 40%(P=0.000),82%vs 84%(P=0.830),and 37%vs 44%(P=0.466)when comparing Group 1 with 2,1h with1n,and 2h with 2n,*** Group 2h,the SVR rates were 34%vs 40%(P=0.701),11%vs 52%(P=0.004),12%vs 50%(P=0.007),7%vs 50%(P=0.003),6%vs 53%(P=0.001),and 0%vs 64%(P=0.000)when comparing patients with high and normalized ALT levels at week 4,8,12,24,48 and 72,*** multiple logistic regression analysis revealed that RVR(OR=7.05;95%CI:3.1-16.05,P=0.000),complete early virological response(cEVR)(OR=17.55;95%CI:6.32-48.76,P=0.000),normalization of ALT at8 wk(OR=3.04;95%CI:1.31-7.06,P=0.008),and at 12 wk(OR=4.21;95%CI:1.65-10.76,P=0.002)were identified as independent significant predictive factors for ***:Normalization of ALT at 8 wk may predict viral response during peginterferon-ribavirin treatment in genotype-1 CHC patients especially without RVR.

关键词： Chronic hepatitis C Genotype-1 Alanine aminotransferase Rapid virological response Sustained virological response,Interferon Ribavirin

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Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma

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World Journal of Gastroenterology 2019年第36期25卷 5515-5529页

作者： Qiang Wang Qi Chen Xia Zhang Xiao-Lan Lu Qin Du Tao Zhu Guo-Yuan Zhang Dong-Sheng Wang Qu-Ming Fan Department of Laboratory Medicine Affiliated Hospital of North Sichuan Medical College Nanchong 637000 Sichuan Province China Faculty of Laboratory Medicine Center for Translational Medicine North Sichuan Medical College Nanchong 637000 Sichuan Province China Department of Laboratory Medicine Affiliated Sichuan Ba-Yi Rehabilitation Center of Chengdu University of TCM Chengdu 610000 Sichuan Province China Department of Laboratory Medicine of the Ninth People’s Hospital of Chongqing Chongqing 400700 China Department of Preventive Medicine North Sichuan Medical College Nanchong 637000 Sichuan Province China

BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP 0.05). When PIVKA-II was combined with the γ-GT/AST rati

关键词： Gamma-glutamyltransferase Aspartate aminotransferase Protein induced by vitamin K absence or antagonist II Alpha-fetoprotein Hepatitis B virus Hepatocellular carcinoma

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Disease progression in chronic hepatitis C patients with normal alanine aminotransferase levels

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World Journal of Gastroenterology 2013年第14期19卷 2256-2261页

作者： Dong Hyun Sinn Geum-Youn Gwak Jae-uk Shin Moon Seok Choi Joon Hyeok Lee Kwang Cheol Koh Seung Woon Paik Byung Chul Yoo Department of Internal Medicine Sanggye Paik HospitalInje University School of Medicine Department of Medicine Samsung Medical CenterSungkyunkwan University School of Medicine

AIM:To investigate whether the disease progression of chronic hepatitis C patients with normal alanine aminotransferase(ALT) levels differs by ALT ***:A total of 232 chronic hepatitis C patients with normal ALT( 26 IU/L(highnormal),respectively(P = 0.043),and it was 1.4% and 4.8% for female patients with baseline ALT levels ≤ 22 IU/L(low-normal) and > 23 IU/L(high-normal),respectively(P = 0.023).ALT levels fluctuated during the follow-up *** the follow-up,more patients with "high-normal" ALT levels at baseline experienced ALT elevation(> 41 IU/L) than did patients with "lownormal" ALT levels at baseline(47.7% vs 27.9%,P = 0.002).The 5 year cumulative incidence of disease progression was significantly lower in patients with persistently "low-normal" ALT levels than "high-normal" ALT levels or those who exhibited an ALT elevation > 41 U/L during the follow-up period(0%,8.3% and 34.3%,P < 0.001).CONCLUSION:A "high normal" ALT level in chronic hepatitis C patients was associated with disease progression,suggesting that the currently accepted normal threshold of serum ALT should be lowered.

关键词： Alanine aminotransferase Upper limits of normal Disease progression Hepatitis C virus Hepatocellular carcinoma

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IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase

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World Journal of Hepatology 2013年第11期5卷 635-641页

作者： Tatsuo Miyamura Tatsuo Kanda Masato Nakamura Xia Jiang Shuang Wu Shingo Nakamoto Shigeru Mikami Nobuo Takada Fumio Imazeki Osamu Yokosuka Department of Gastroenterology and Nephrology Chiba University Graduate School of Medicine Department of Internal Medicine Kikkoman General Hospital Department of Internal Medicine Toho University Sakura Medical Centre Safety and Health Organization Chiba University

AIM:To examine the association between the interleukin 28B(IL-28B)genotype and treatment response in hepatitis C virus(HCV)-infected patients with persistently normal alanine aminotransferase(PNALT).METHODS:We compared the treatment response of HCV-infected patients with PNALT to that of patients with *** February 2010 and April2013,278 patients infected with HCV were enrolled in this *** of the patients were treated with peginterferon-alpha 2a or 2b plus *** addition,180μg of peginterferon alpha-2a or 1.5μg/kg peginterferon alpha-2b per week plus weight-based ribavirin(600-1000 mg/d)were typically administered for 24 wk to HCV genotype 2-infected patients or for 48-72 wk to HCV genotype 1-infected *** all of the patients,the IL-28B rs8099917 genotype was determined using a TaqMan single-nucleotide polymorphism *** RNA was measured using the COBAS TaqMan HCV ***:Female patients were dominant in the PNALT group(P<0.0001).Among 72 HCV genotype 1-infected patients with PNALT,the early virologic response(EVR)rates(P<0.01)and the sustained virologic response(SVR)rates(P<0.01)were higher in patients with the IL-28B TT genotype than in those with the IL-28B TG/GG *** HCV genotype 1-infected patients with PNALT,multivariate logistic-regression analysis showed that SVR was independently predicted by the IL-28B rs8099917 TT type(P<0.05)and having an EVR(P<0.01).The IL-28B rs8099917 TT genotype strongly correlated with treatment response in HCV genotype 1-infected Asian patients with ***:The IL-28B genotype may be useful for selecting HCV genotype 1-infected patients with PNALT who should receive interferon-based treatment.

关键词： Hepatitis C virus Interleukin 28B Persistent normal alanine aminotransferase levels Standard of care Treatment response

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Elevated alanine aminotransferase activity is not associated with dyslipidemias,but related to insulin resistance and higher disease grades in non-diabetic non-alcoholic fatty liver disease

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Asian Pacific Journal of Tropical Biomedicine 2012年第9期2卷 702-706页

作者： Mohammad Ebrahim Ghamar-Chehreh Mohsen Amini Hossein Khedmat Seyed Moayed Alavian Fatemeh Daraei Reza Mohtashami Reza Hadi Bent-Al-Hoda Beyram Saeed Taheri The Internist Research Center Baqiyatallah Research Center for Gastroenterology and Liver Diseases Baqiyatallah University of Medical Sciences Dr.Taheri Medical Research Group

Objective:To explore demographic and metabolic factors associated with increased alanine aminotransferase(ALT)activity in non-diabetic non-alcoholic fatty liver disease(NAFLD)***:Overall 372 patients who consecutively attended to Gastroenterology Clinic of Baqiyatallah University of Medical Sciences,Tehran,Iran awere diagnosed as NAFLD entered into *** criteria were having diabetes mellitus and fasting blood glucose over126 mg/dL,active hepatitis B virus infection,having hepatitis C virus positive serology,and to be under corticosteroid *** levels were considered pathologically high when it was over30 IU/L for men and over 19 IU/L for ***:Bivariate analyses using t test and chisquare test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations(P=0.003).Moreover,these patients represented significantly higher homeostatic model assessment levels(P=0.003),levels of serum insulin(P=0.002),fasting blood glucose(P<0.001),and uric acid(P=0.02).The prevalence of insulin resistance was also higher in patients with increased serum ALT *** logistic regression models showed that ultrasonographic grading of NAFLD(P=0.027)and insulin resistance(P=0.013)were the only variables significantly associated with abnormal ALT ***:This study shows that the associations of increased ALT serum levels in NAFLD patients are different from what are supposed *** excluding diabetic patients from our population,we find that increased ALT levels are not associated with dyslipidemias but are independently associated with insulin resistance and NAFLD grading on ultrasonographic *** studies are needed to confirm our results.

关键词： Alanine aminotransferase Non-alcoholic fatty liver disease Insulin resistance Fasting blood glucose Ultrasonographic evaluation Diabetes mellitus Metabolic factor Serum insulin Dyslipidemia

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26S proteasome inhibitors inhibit dexamethasone-dependent increase of tyrosine aminotransferase and tryptophan 2,3-dioxygenase mRNA levels in primary cultured rat hepatocytes

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Journal of Biophysical Chemistry 2012年第4期3卷 348-356页

作者： Mizuho Harashima Masashi Hyuga Youko Nagaoka Chieko Saito Minako Furukawa Taiichiro Seki Toyohiko Ariga Nana Kawasaki Shingo Niimi Department of Nutrition and Physiology Nihon University College of Bioresource Sciences Fujisawa Japan Division of Biological Chemistry and Biologicals National Institute of Health Sciences Tokyo Japan

Dexamethasone (Dex), a ligand for transcriptional enhancement of tyrosine aminotransferase (TAT) and tryptophan 2,3-dioxygenase (TO) genes, (100 nM) maximally increased these mRNA levels at 12 h and 7 h in primary cultured rat hepatocytes and the nuclear fraction, respectively. Lactacystin (5 μM) and epoxomicin (0.5 μM), 26S proteasome inhibitors, significantly suppressed the Dex-dependent maximum increase of TAT and TO mRNA levels in the cells and the nuclear fraction. Electrophoretic mobility shift assay demonstrated that lactacystin did not affect binding of glucocorticoid receptor to glucocorticoid responsive element. Furthermore, lactacystin did not affect the activation of GRE luciferase reporter by Dex transfected to the cells. The results demonstrate that 26S proteasome is positively involved in the Dex-dependent increase of TAT and TO mRNA levels in the cells and suggest that the mechanism of action of 26S proteasome may be degradation of some RNase(s), which breaks down TAT and TO mRNAs.

关键词： Glucocorticoid 26S proteasome Inhibitor Tyrosine aminotransferase Tryptophan 2 3-Dioxygenase Genes

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Mining of aminotransferase gene ota3 from Bacillus pumilus W3 via genome analysis,gene cloning and expressing for compound bioamination

Mining of aminotransferase gene ota3 from Bacillus pumilus W...

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华东六省一市生物化学与分子生物学会联盟2019年学术与教学交流会

作者： Lixin Zhai Shaolan Yang Di Meng Qiaopeng Tian Xiangru Liao Key Laboratory of Industrial Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan University

aminotransferases are widely employed as biocatalysts to produce chiral amines and biologically active pharmaceuticals via asymmetric *** complete Bacillus pumilus W3 genome is available from NCBI(National Center for Biotechnology Information).One hypothetical protein co-BPTA as pyridoxal 5’-phosphate dependent enzymes class Ⅳ(PLPDE;aminotransferase class Ⅳ) was chosen from Bacillus pumilus W3,The sequence of ota3 shares highest sequence identity(24.7%) with the first(R)-selective aminotransferase from Arthrobacter *** *** native and codon-optimised ω-BPAT genes were recombinantly expressed,and the purified proteins had a molecular mass of ～33.4 ***,the relationships between comprehensive performance of ω-BPTA(activity and stability) and reaction conditions(pH and temperature) were investigated by carrying out a single-variable test with phenethylamine and pyruvate as donor and acceptor *** tests with(S)-and(R)-a-phenethylamine revealed its(R)-*** optimal conditions for catalytic reaction were 45℃ and pH 7.0,and ω-BPAT retained stability at 20℃ and pH ***,co-BPAT is a novel(R)-selective aminotransferase with great potential as a universal *** method provided an approach for the rapid screening of transaminases,and a reference for future rational engineering of co-BPTA to improve substrate specificity and conversion efficiency.

关键词： aminotransferase Genome analysis Bioinformatics Chiral amine Bacillus pumilus W3

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