DOCSLIB.ORG

Causes and Evaluation of Mildly Elevated Liver Transaminase Levels ROBERT C

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Causes and Evaluation of Mildly Elevated Liver Transaminase Levels ROBERT C Causes and Evaluation of Mildly Elevated Liver Transaminase Levels ROBERT C. OH, LTC, MC, USA, and THOMAS R. HUSTEAD, LTC, MC, USA Tripler Army Medical Center Family Medicine Residency Program, Honolulu, Hawaii Mild elevations in levels of the liver enzymes alanine transaminase and aspartate transaminase are commonly dis- covered in asymptomatic patients in primary care. Evidence to guide the diagnostic workup is limited. If the history and physical examination do not suggest a cause, a stepwise evaluation should be initiated based on the prevalence of diseases that cause mild elevations in transaminase levels. The most common cause is nonalcoholic fatty liver disease, which can affect up to 30 percent of the population. Other common causes include alcoholic liver disease, medication- associated liver injury, viral hepatitis (hepatitis B and C), and hemochromatosis. Less common causes include α1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease. Extrahepatic conditions (e.g., thyroid disorders, celiac disease, hemolysis, muscle disorders) can also cause elevated liver transaminase levels. Initial testing should include a fasting lipid profile; measurement of glucose, serum iron, and ferritin; total iron-binding capacity; and hepa- titis B surface antigen and hepatitis C virus antibody testing. If test results are normal, a trial of lifestyle modification with observation or further testing for less common causes is appropriate. Additional testing may include ultrasonog- raphy; measurement of α1-antitrypsin and ceruloplasmin; serum protein electrophoresis; and antinuclear antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1 testing. Referral for further evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for six months or more. (Am Fam Physi- cian. 2011;84(9):1003-1008. Copyright © 2011 American Academy of Family Physicians.) ▲ Patient information: easurement of liver enzymes skeletal muscles and erythrocytes. Therefore, A handout on elevated is common in primary care, elevations in ALT levels generally are more liver enzymes, written by the authors of this article, and has likely increased the specific for hepatic injury. At times, the is provided on page 1010. prevalence of asymptomatic AST/ALT ratio can suggest certain disease M patients with mild elevations in alanine patterns. For instance, a ratio greater than transaminase (ALT) and aspartate trans- 2 suggests alcoholic liver disease, whereas aminase (AST) levels. The National Health nonalcoholic fatty liver disease is usually and Nutrition Examination Survey found associated with a ratio of less than 1. A ratio elevated liver transaminase levels in up greater than 4 may suggest Wilson disease.6 to 8.9 percent of the survey population.1,2 When the AST/ALT ratio does not suggest Although there are several published guide- an etiology, asymptomatic elevation of liver lines for the workup of asymptomatic trans- transaminase levels can be categorized into aminase level elevations,3-5 evidence from common hepatic, less common hepatic, and large prospective studies is sparse. Under- extrahepatic causes (Table 1).3-5 standing the basic disease processes that cause mildly elevated liver transaminase Common Causes levels (i.e., less than five times the upper NONALCOHOLIC FATTY LIVER DISEASE limit of normal) and the epidemiology of Nonalcoholic fatty liver disease is typically each disease can help guide the patient his- divided into two subtypes: hepatic steatosis tory, physical examination, and further and nonalcoholic steatohepatitis. Hepatic diagnostic testing. steatosis is the more common and more benign type. It generally does not progress Etiologies to severe liver disease or cirrhosis. Nonal- Hepatocellular damage releases ALT and coholic steatohepatitis carries an increased AST into the bloodstream. ALT is found risk of progression to end-stage liver disease, primarily in the liver; AST is also found in cirrhosis, and hepatocellular carcinoma. Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2011 American Academy of Family Physicians. For the private, noncommercial Novemberuse 1, of2011 one individual◆ Volume user 84, of Number the Web site. 9 All other rights reserved.www.aafp.org/afp Contact [email protected] for copyright questionsAmerican and/or permission Family Physician requests. 1003 SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence Clinical recommendation rating References A stepwise diagnostic approach should be initiated in patients with elevated liver transaminase levels if C 3, 5 the history and physical examination do not suggest a cause. If the history and physical examination do not suggest a cause of elevated liver transaminase levels, C 3-5, 31 testing should be repeated in two to four weeks. A fasting lipid profile and glucose level should be ordered if the metabolic syndrome or nonalcoholic C 3-5 fatty liver disease is suspected. Observation with lifestyle modification is appropriate if the initial history, physical examination, and C 3 workup do not suggest a cause of elevated liver transaminase levels. Referral to a gastroenterologist for potential liver biopsy is reasonable in patients with persistent C 3 unexplained elevation of liver transaminase levels for six months or more. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease- oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp. org/afpsort.xml. Table 1. Causes of Elevated Liver Transaminase Levels, Clinical Clues, and Initial Diagnostic Testing Etiology Clinical clues Initial diagnostic testing Common Alcohol-related Excessive alcohol consumption Aspartate transaminase/alanine transaminase ratio, γ-glutamyl transpeptidase level Hemochromatosis Family history Serum iron and ferritin levels, total iron-binding capacity Hepatitis B Immigration from endemic countries, Hepatitis B surface antigen testing nonmonogamous sexual activity, injection drug use Hepatitis C Injection drug use, human immunodeficiency virus Hepatitis C virus antibody testing infection, blood transfusion before 1992 Medications Polypharmacy, certain herbal preparations History Nonalcoholic fatty Evidence of metabolic syndrome (high triglyceride Fasting lipid profile, glucose level; consider liver disease levels, low high-density lipoprotein levels, increased ultrasonography waist circumference, elevated glucose levels) Less common α1-antitrypsin Early-onset emphysema, family history Serum α1-antitrypsin level deficiency Autoimmune Women with autoimmune disorders Serum protein electrophoresis; antibodies to liver/kidney hepatitis microsomal antibody type 1, antinuclear antibody, and smooth muscle antibody testing Wilson disease Younger than 40 years, neuropsychiatric symptoms, Serum ceruloplasmin level Kayser-Fleischer rings Extrahepatic Celiac disease Diarrhea, abdominal pain, malabsorption Tissue transglutaminase antibody testing Hemolysis Glucose-6-phosphate dehydrogenase deficiency, Lactate dehydrogenase and haptoglobin levels, sickle cell anemia, infection reticulocyte count Muscular disorders Muscle weakness and pain, strenuous exercise Creatine kinase and aldolase levels Thyroid disorders Signs and symptoms of hypo- or hyperthyroidism Thyroid-stimulating hormone level Information from references 3 through 5. Nonalcoholic fatty liver disease is the leading cause of mild in patients who are obese or who have diabetes mellitus, transaminase elevations, and is becoming more prevalent hypertriglyceridemia, or the metabolic syndrome.8 as the obesity rate increases. It is estimated that 30 percent Ultrasonography, computed tomography, and mag- of U.S. adults have nonalcoholic fatty liver disease, and netic resonance imaging have fair to excellent sensitiv- that up to 3 to 6 percent have nonalcoholic steatohepati- ity and specificity for identifying hepatic steatosis7,9,10 tis.7 Nonalcoholic fatty liver disease should be considered (Table 210). Ultrasonography is the most common test 1004 American Family Physician www.aafp.org/afp Volume 84, Number 9 ◆ November 1, 2011 Elevated Liver Transaminase Levels for nonalcoholic fatty liver disease because of its wide availability and low cost.5,11 Imaging may assist in the Table 2. Accuracy of Imaging in Identifying diagnosis of nonalcoholic fatty liver disease, but not Hepatic Steatosis in the differentiation of hepatic steatosis from nonal- coholic steatohepatitis. A definitive diagnosis of non- Modality Sensitivity (%) Specificity (%) alcoholic steatohepatitis is made when liver biopsy Computed tomography 46.1 to 72.0 88.1 to 94.6 demonstrates inflammation and evidence of fibrosis Magnetic resonance 82.0 to 97.4 76.1 to 95.3 7 not typically seen in hepatic steatosis. imaging Magnetic resonance 72.7 to 88.5 92.0 to 95.7 ALCOHOL spectroscopy In a study of 256 asymptomatic Swedish patients with Ultrasonography 73.3 to 90.5 69.6 to 85.2 mildly elevated liver transaminase levels, alcohol was found to be the cause in 10 percent.12 The most impor- Information from reference 10. tant way to make the diagnosis is through an accurate history. Biopsy alone cannot differentiate alcoholic liver disease from nonalcoholic fatty liver disease. An AST/ALT ratio greater than 2 supports a diagnosis of Table 3. Selected Medications Associated with Elevated Liver Transaminase Levels alcoholic liver disease,
Load more

Recommended publications
  • Tbamitchodral L Alizaion of the 4Aminobutyrate-2-&Oxoglutarate
    5d.em. J. (lWg77) 161,9O.-307 3O1 Printed in Great Britain Tbamitchodral L alizaion of the 4Aminobutyrate-2-&Oxoglutarate Transminase from Ox Brait By INGER SCHOUSDOE,* BIRGIT 1MO* and ARNE SCHOUSBOEt Department ofBDahemistry At andC*, University ofCopenhagen, 2200 Copenhagen M, Denark (Receved 4 June 1976) In order to determine the intramitochondrial location of 4-aminobutyrate transaminase, mitochondria were prepared from ox brain and freed from myelin and syiaptosomes by using conventional demitygradient-centrifugation techniques, and the purity was checked electron-microscopically. Iner and outer mimbrenes and matrix were prepared from the mitochondria by large-amplitude sweling and subsequent density-gradient centrfugationt The fractions were characterized by using both electron microscopy and differnt marker enzymes. From the specific activity of the 4-aminobutyrate transaminase in the submitochondrial fractions it was concluded that this enzyme is associated with the inner mitochondrial membrane. It is generally agreed that the 4-aminobutyrate-2- pyridoxal phosphate were from Sigma Chemical oxoglutarate transaminase (EC2.6.1.19) from brain is Co., St. Louis, MO, U.S.A. Ficoll was from mainly associated with free mitochondria (Salganicoff Pharmacia, Uppsala, Sweden, and crystallized & De Robertis, 1963, 1965; van den Berget al., 1965; bovine serum albumin was from BDH Biochemicals, van Kempen et at., 1965; Balazs et al., 1966; Poole, Dorset, U.K. 4-Amino[1-'4C]butyrate (sp. Waksman et al., 1968; Reijnierse et al., 1975), radioactivity 50mCi/mmol) and [1-14qtyramine (sp. and a preparation of a crude mitochondrial fraction radioactivity 9mCi/mmol) were obtained from was used by Schousboe et al. (1973) and Maitre et al.
    [Show full text]
  • Neuroleptic Malignant Syndrome: Another Medical Cause of Acute Abdomen T.C.N
    Postgraduate Medical Journal (1989) 65, 653 - 655 Postgrad Med J: first published as 10.1136/pgmj.65.767.653 on 1 September 1989. Downloaded from Missed Diagnosis Neuroleptic malignant syndrome: another medical cause of acute abdomen T.C.N. Lo, M.R. Unwin and I.W. Dymock Department ofMedicine, Stepping Hill Hospital, Stockport, UK. Summary: We present a patient with neuroleptic malignant syndrome and intestinal pseudo- obstruction misdiagnosed as being secondary to septicaemia. The management of the patient is discussed with emphasis on the role of creatine kinase and liver function tests. Introduction Neuroleptic malignant syndrome (NMS) is an occas- (92% neutrophils), serum sodium 130 mmol/l, potas- ional but potentially lethal idiosyncratic complication sium 5.1 mmol/l, urea 8.8 mmol/l, creatinine 79 1tmol/ ofneuroleptic drugs.'"2 By February 1989 the Commit- 1, bilirubin 15 Amol/l, alanine transaminase 837 IU/i tee on Safety of Medicines had received reports of 99 (normal 7-45), aspartate transaminase 392 IU/l (nor- cases. (Committee on Safety of Medicines, personal mal 9-41), gamma glutamyl transferase 15 IU/I (nor- Protected by copyright. Communication). It is thought that the condition is mal <65), alkaline phosphatase 62 IU/I (normal underdiagnosed.34 We report on a case of NMS of 35-125). Serial electrocardiograms showed sinus which the presenting features and therapeutic comp- tachycardia with no acute change. Abdominal X-ray lications occurring during the course of the illness revealed marked gaseous distension ofsmall and large served to further our knowledge in this condition. bowels with multiple fluid levels seen on decubitus films.
    [Show full text]
  • Liver Intracellular L-Cysteine Concentration Is Maintained After Inhibition of the Trans-Sulfuration Pathway by Propargylglycine in Rats
    Downloaded from British Journal of Nutrition (1997), 78, 823-831 823 https://www.cambridge.org/core Liver intracellular L-cysteine concentration is maintained after inhibition of the trans-sulfuration pathway by propargylglycine in rats BY ANA TRIGUERO', TERESA BARBER', CONCHA GARC~A', . IP address: INMACULADA R. PUERTES', JUAN SASTRE~AND JUAN R. VIRA' 'Departamento de Bioquhica y Biologia Molecular and 2Departamento de Fisiologfa, Facultades de Farmucia y Medicina, Universidad de Valencia, 46010-Valencia, Spain 170.106.33.14 (Received 31 January 1997 - Revised 24 April I997 - Accepted 7 May 1997) , on 26 Sep 2021 at 14:28:26 To study the fate of L-cysteine and amino acid homeostasis in liver after the inhibition of the trans- sulfuration pathway, rats were treated with propargylglycine (PPG). At 4 h after the administration of PPG, liver cystathionase (EC 4.4.1.1) activity was undetectable, L-cystathionine levels were significantly higher, L-cysteine was unchanged and GSH concentration was significantly lower than values found in livers from control rats injected intraperitoneally with 0.15 M-NaCl. The hepatic levels of amino acids that are intermediates of the urea cycle, L-ornithine, L-citrulline and L-arginine and blood urea were significantly greater. Urea excretion was also higher in PPG-treated rats when , subject to the Cambridge Core terms of use, available at compared with control rats. These data suggest a stimulation of ureagenesis in PPG-treated rats. The inhibition of y-cystathionase was reflected in the blood levels of amino acids, because the L- methionine :L-cyst(e)ine ratio was significantly higher in PPG-treated rats than in control rats; blood concentration of cystathionine was also greater.
    [Show full text]
  • Independent Effect of Alanine Transaminase on the Incidence Of
    Clinica Chimica Acta 495 (2019) 54–59 Contents lists available at ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/cca Independent effect of alanine transaminase on the incidence of type 2 diabetes mellitus, stratified by age and gender: A secondary analysis based T on a large cohort study in China Feng Gaoa, Xie-lin Huangb, Xue-Pei Jianga, Min Xuea, Ya-Ling Lia, Xin-Ran Lina, Yi-Han Chena, ⁎ Zhi-Ming Huanga, a Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China b Department of Gastroenterology Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China ARTICLE INFO ABSTRACT Keywords: Background: Previous studies have revealed that alanine aminotransferase (ALT) may be one of the risk factors Alanine transaminase of developing diabetes. We aimed to demonstrate the independent effect of ALT on incident diabetes and to Diabetes investigate whether the association between ALT and incident diabetes is modified by age and gender in the Age general Chinese population. Sex Methods: The present study was a retrospective cohort study, including 210,051 Chinese adult participants. The primary outcome was developing diabetes. The serum ALT activities were stratified by quintiles. We obtained data from ‘DATADRYAD’ website and used the data for secondary analysis. Results: At a median follow-up of 3.0 y, 4144 of 210,051 (1.97%) participants developed diabetes. After ad- justment for potential confounders, a significantly higher risk of the incident diabetes (HR: 1.43, 95% CI: 1.25–1.63) was found in participants in the fifth quintile (Q5, ≥31 U/L) compared to those in the first to fourth quintiles (Q1–4) for ALT activities.
    [Show full text]
  • Gamma Glutamyl Transferase (GGT) NCD 190.32
    Medicare National Coverage Determination (NCD) Policy TRANSFERASE GAMMA GLUTAMYL Summary: Gamma Glutamyl Transferase (GGT) NCD 190.32 The terms of Medicare National Coverage Determinations (NCDs) are binding on all fee-for-service (Part A/B) Medicare Administrative Contractors (MACs) and Medicare Advantage (MA) plans. NCDs are not binding, however, on Medicaid and other governmental payers, nor are they binding on commercial payers in their non-MA lines of business. Item/Service Description* Gamma Glutamyl Transferase (GGT) is an intracellular enzyme that appears in blood following leakage from cells. Renal tubules, liver, and pancreas contain high amounts, although the measurement of GGT in serum is almost always used for assessment of hepatobiliary function. Unlike other enzymes which are found in heart, skeletal muscle, and intestinal mucosa as well as liver, the appearance of an elevated level of GGT in serum is almost always the result of liver disease or injury. It is specifically useful to differentiate elevated alkaline phosphatase levels when the source of the alkaline phosphatase increase (bone, liver, or placenta) is unclear. The combination of high alkaline phosphatase and a normal GGT does not, however, rule out liver disease completely. As well as being a very specific marker of hepatobiliary function, GGT is also a very sensitive marker for hepatocellular damage. Abnormal concentrations typically appear before elevations of other liver enzymes or bilirubin are evident. Obstruction of the biliary tract, viral infection (e.g., hepatitis, mononucleosis), metastatic cancer, exposure to hepatotoxins (e.g., organic solvents, drugs, alcohol), and use of drugs that induce microsomal enzymes in the liver (e.g., cimetidine, barbiturates, phenytoin, and carbamazepine) all can cause a moderate to marked increase in GGT serum concentration.
    [Show full text]
  • Como As Enzimas Agem?
    O que são enzimas? Catalizadores biológicos - Aceleram reações químicas específicas sem a formação de produtos colaterais PRODUTO SUBSTRATO COMPLEXO SITIO ATIVO ENZIMA SUBSTRATO Características das enzimas 1 - Grande maioria das enzimas são proteínas (algumas moléculas de RNA tem atividade catalítica) 2 - Funcionam em soluções aquosas diluídas, em condições muito suaves de temperatura e pH (mM, pH neutro, 25 a 37oC) Pepsina estômago – pH 2 Enzimas de organismos hipertermófilos (crescem em ambientes quentes) atuam a 95oC 3 - Apresentam alto grau de especificidade por seus reagentes (substratos) Molécula que se liga ao sítio ativo Região da enzima e que vai sofrer onde ocorre a a ação da reação = sítio ativo enzima = substrato 4 - Peso molecular: varia de 12.000 à 1 milhão daltons (Da), são portanto muito grandes quando comparadas ao substrato. 5 - A atividade catalítica das Enzimas depende da integridade de sua conformação protéica nativa – local de atividade catalítica (sitio ativo) Sítio ativo e toda a molécula proporciona um ambiente adequado para ocorrer a reação química desejada sobre o substrato A atividade de algumas enzimas podem depender de outros componentes não proteicos Enzima ativa = Holoenzimas Parte protéica das enzimas + cofator Apoenzima ou apoproteína •Íon inorgânico •Molécula complexa (coenzima) Covalentemente ligados à apoenzima GRUPO PROSTÉTICO COFATORES Elemento com ação complementar ao sitio ativo as enzimas que auxiliam na formação de um ambiente ideal para ocorrer a reação química ou participam diretamente dela
    [Show full text]
  • The Proteins
    The Proteins The name protein is derived from Greek word Proteioes which means first because proteins essential for growth and maintenance of life. Proteins: are complex nitrogenous polymers present in all living matter, contain C,H,O and nitrogen, also contain sulfur, phosphorous, zinc, copper and iron. -- are made up of hundreds or thousands of smaller units called amino acids which are attached to one another in long chains. -- there are 20 different types of amino acids that can be combined to make a protein. -- the sequence of amino acids determines each protein’s unique 3-dimensional structure and its specific function. We need protein in diet 1. repair cells and make new ones. 2. important for growth and development in children, teens, and pregnant women. Amino acids Amino acids : are organic acids containing an amino group (NH2) and a carboxylic acid (COOH) group. The side chain can be, aliphatic, aromatic, heterocyclic, containing sulphar group . All amino acids are L-amino acids configuration. Proteins are made up of 20 amino acids in different sequences and numbers. Classification: Amino acids are classified into three groups: 1. neutral amino acids: are the largest group which are divided into: a.aliphatic amino acids ( glycine,valine,alanine,leucine,isoleucine). b. aromatic amino acids ( tyrosine, phenylalanine). c. heterocyclic amino acids ( tryptophan, histidine). d. sulpher containing amino acid ( cystine , cysteine , methionine ) 2. Acidic amino acids ( aspartic acid , glutamic acid ) 3. Basic amino acids (Lysine , arginine). Essential amino acids : Amino acids are not synthesized in the body and are essential as constituents of tissue proteins , therefore it must be supplied in food.
    [Show full text]
  • Supplementary Information
    Supplementary information (a) (b) Figure S1. Resistant (a) and sensitive (b) gene scores plotted against subsystems involved in cell regulation. The small circles represent the individual hits and the large circles represent the mean of each subsystem. Each individual score signifies the mean of 12 trials – three biological and four technical. The p-value was calculated as a two-tailed t-test and significance was determined using the Benjamini-Hochberg procedure; false discovery rate was selected to be 0.1. Plots constructed using Pathway Tools, Omics Dashboard. Figure S2. Connectivity map displaying the predicted functional associations between the silver-resistant gene hits; disconnected gene hits not shown. The thicknesses of the lines indicate the degree of confidence prediction for the given interaction, based on fusion, co-occurrence, experimental and co-expression data. Figure produced using STRING (version 10.5) and a medium confidence score (approximate probability) of 0.4. Figure S3. Connectivity map displaying the predicted functional associations between the silver-sensitive gene hits; disconnected gene hits not shown. The thicknesses of the lines indicate the degree of confidence prediction for the given interaction, based on fusion, co-occurrence, experimental and co-expression data. Figure produced using STRING (version 10.5) and a medium confidence score (approximate probability) of 0.4. Figure S4. Metabolic overview of the pathways in Escherichia coli. The pathways involved in silver-resistance are coloured according to respective normalized score. Each individual score represents the mean of 12 trials – three biological and four technical. Amino acid – upward pointing triangle, carbohydrate – square, proteins – diamond, purines – vertical ellipse, cofactor – downward pointing triangle, tRNA – tee, and other – circle.
    [Show full text]
  • Relationship of Liver Enzymes to Insulin Sensitivity and Intra-Abdominal Fat
    Diabetes Care Publish Ahead of Print, published online July 31, 2007 Relationship of Liver Enzymes to Insulin Sensitivity and Intra-abdominal Fat Tara M Wallace MD*, Kristina M Utzschneider MD*, Jenny Tong MD*, 1Darcy B Carr MD, Sakeneh Zraika PhD, 2Daniel D Bankson MD, 3Robert H Knopp MD, Steven E Kahn MB, ChB. *Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System 1Obstetrics and Gynecology, University of Washington, Seattle, WA 2Pathology and Laboratory Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, WA 3Harborview Medical Center, University of Washington, Seattle, WA Running title: Liver enzymes and insulin sensitivity Correspondence to: Steven E. Kahn, M.B., Ch.B. VA Puget Sound Health Care System (151) 1660 S. Columbian Way Seattle, WA 98108 Email: [email protected] Received for publication 18 August 2006 and accepted in revised form 29 June 2007. 1 Copyright American Diabetes Association, Inc., 2007 Liver enzymes and insulin sensitivity ABSTRACT Objective: To determine the relationship between plasma liver enzyme concentrations, insulin sensitivity and intra-abdominal fat (IAF) distribution. Research Design and Methods: Plasma gamma-glutamyl transferase (GGT), aspartate transaminase (AST), alanine transaminase (ALT) levels, insulin sensitivity (SI), IAF and subcutaneous fat (SCF) areas were measured on 177 non-diabetic subjects (75M/102, 31-75 2 -5 years) with no history of liver disease. Based on BMI (< or ≥27.5 kg/m ) and SI (< or ≥7.0x10 min-1 pM-1) subjects were divided into lean insulin sensitive (LIS, n=53), lean insulin resistant (LIR, n=60) and obese insulin resistant (OIR, n=56) groups.
    [Show full text]
  • GFAT and PFK Genes Show Contrasting Regulation of Chitin
    www.nature.com/scientificreports OPEN GFAT and PFK genes show contrasting regulation of chitin metabolism in Nilaparvata lugens Cai‑Di Xu1,3, Yong‑Kang Liu2,3, Ling‑Yu Qiu2, Sha‑Sha Wang2, Bi‑Ying Pan2, Yan Li2, Shi‑Gui Wang2 & Bin Tang2* Glutamine:fructose‑6‑phosphate aminotransferase (GFAT) and phosphofructokinase (PFK) are enzymes related to chitin metabolism. RNA interference (RNAi) technology was used to explore the role of these two enzyme genes in chitin metabolism. In this study, we found that GFAT and PFK were highly expressed in the wing bud of Nilaparvata lugens and were increased signifcantly during molting. RNAi of GFAT and PFK both caused severe malformation rates and mortality rates in N. lugens. GFAT inhibition also downregulated GFAT, GNPNA, PGM1, PGM2, UAP, CHS1, CHS1a, CHS1b, Cht1-10, and ENGase. PFK inhibition signifcantly downregulated GFAT; upregulated GNPNA, PGM2, UAP, Cht2‑4, Cht6‑7 at 48 h and then downregulated them at 72 h; upregulated Cht5, Cht8, Cht10, and ENGase; downregulated Cht9 at 48 h and then upregulated it at 72 h; and upregulated CHS1, CHS1a, and CHS1b. In conclusion, GFAT and PFK regulated chitin degradation and remodeling by regulating the expression of genes related to the chitin metabolism and exert opposite efects on these genes. These results may be benefcial to develop new chitin synthesis inhibitors for pest control. Chitin is a linear polymer composed of N-acetylglucosamine units connected by β-1, 4-glycoside bonds and is the second most abundant biopolymer in nature. It is widely distributed in fungi, nematodes, and arthropods1. In insects, chitin is a major component of the exoskeleton, trachea, and the peritrophic matrix that lines the midgut epithelium1–4.
    [Show full text]
  • Diagnostic Value of the Γ-Glutamyltransferase and Alanine
    www.nature.com/scientificreports OPEN Diagnostic value of the γ‑glutamyltransferase and alanine transaminase ratio, alpha‑fetoprotein, and protein induced by vitamin K absence or antagonist II in hepatitis B virus‑related hepatocellular carcinoma Guangrong Wang1,2,3,4, Xiaolan Lu1,2,4, Qin Du1,2, Guoyuan Zhang1,2, Dongsheng Wang1,3, Qiang Wang1,2,3* & Xiaolan Guo1,2,3* Hepatocellular carcinoma is a common type of malignancy with a poor prognosis. Identifcation and utilisation of markers for monitoring and diagnosis are urgently needed. Alpha‑fetoprotein (AFP) and Protein Induced by Vitamin K Absence or Antagonist‑II (PIVKA‑II) have been proved to be efcient biomarkers for hepatitis B virus (HBV)‑related hepatocellular carcinoma (HCC). The combination of the two markers could improve the detection rate. However, these indicators cannot meet the need of clinical diagnosis.It is necessary to discover novel serological markers and more cost‑efective, appropriate combination of these markers for the diagnosis and surveillance of HBV‑related HCC. Accordingly, in this study, we aimed to evaluate the diagnostic value of γ‑glutamyltransferase (γ‑GT) to alanine amino transferase (ALT) ratio alone or in combination with AFP and PIVKA‑II for HBV‑ related HCC. 234 patients with HBV‑related HCC and 396 patients with chronic hepatitis B (CHB) were enrolled in this study and approved by the institutional review board. Our results showed levels of AFP and PIVKA‑II, and γ‑GT/ALT ratio in cases with early‑stage HCC, HCC, HCC plus HBV DNA positivity, and HCC plus HBV DNA negativity were higher than those in the corresponding CHB control group.
    [Show full text]
  • Alanine Transaminase Assay (ALT) Catalog #8478 100 Tests in 96-Well Plate
    Alanine Transaminase Assay (ALT) Catalog #8478 100 Tests in 96-well plate Product Description Alanine Aminotransferase (ALT), also known as serum glutamic-pyruvic transaminase (SGPT), catalyzes the reversible transfer of an amino group from alanine to α-ketoglutarate. The products of this transamination reaction are pyruvate and glutamate. ALT is found primarily in liver and serum, but occurs in other tissues as well. Significantly elevated serum ALT levels often suggest the existence of medical problems, such as hepatocellular injury, hepatitis, diabetes, bile duct problem and myopathy. This colorimetric assay is based on the oxidization of NADH to NAD in the presence of pyruvate and lactate dehydrogenase. The ALT activity is determined by assaying the rate of NADH oxidation, which is proportional to the reduction in absorbance at 340nm over time (ΔOD340nm/min). Kit Components Cat. No. # of vials Reagent Quantity Storage 8478a 1 Assay buffer 10 mL -20°C 8478b 1 ALT standard 10 µL -20°C 8478c 1 Substrate mix 1.0 mL -20°C 8478d 1 Cofactor 0.8 mL -20°C 8478e 1 Enzyme 0.2 mL -80°C Product Use The ALT kit measures the alanine transaminase activity of different types of samples, such as serum, plasma and tissues. ALT is for research use only. It is not approved for human or animal use, or for application in in vitro diagnostic procedures. Quality Control Serially diluted alanine transaminase solutions with concentrations ranging from 0.03125 to 1.0 U/mL are measured with the ScienCell™ Alanine Transaminase Assay kit. The decrease in OD340nm is monitored as a function of time (Figure 1) and the resulting standard of ∆OD340nm/min vs alanine transaminase activity are plotted (Figure 2).
    [Show full text]