Diagnostic Value of Serum IL-12, CDT, HGF and Endotoxin in Different Stages of Alcoholic Liver Disease / 胃肠病学

Background: The incidence of alcoholic liver disease (ALD) is increasing year by year, and is lack of specific diagnostic indicators. Exploring the trend of molecular markers in different stages of ALD is of great significance for its diagnosis and treatment. Aims: To investigate the levels and diagnostic value of serum interleukin-12 (IL-12), carbohydrate-deficient transferrin (CDT), hepatocyte growth factor (HGF) and endotoxin in different stages of ALD. Methods: Nineteen patients with alcoholic cirrhosis (AC), 14 alcoholic hepatitis (AH), 16 alcoholic fatty liver (AFL), 16 subclinical patients from July 2017 to January 2018 at the Second Affiliated Hospital of Baotou Medical College were enrolled, and 15 healthy volunteers were served as healthy controls. Serum IL-12, CDT, HGF levels were detected by ELISA method, and serum endotoxin was detected by limulus test. Diagnostic value of IL-12, CDT for ALD was analyzed by ROC curve. Results: Serum IL-12, endotoxin were significantly increased in AC, AH groups than in AFL, subclinical patients, healthy controls (P<0.05); serum CDT level was significantly increased in AC, AH, AFL, subclinical patients than in healthy controls (P<0.05); serum HGF was significantly increased in AC patients than in AH, AFL, subclinical patients and healthy controls (P<0.05). Serum IL-12, CDT, HGF were positively correlated with serum endotoxin in ALD patients (P<0.05). When the cut-off value of serum IL-12, CDT were 55.06 pg/mL, 354.41 pg/mL, respectively, sensitivity for diagnosing ALD were 0.86, 0.67, respectively, specificity were 0.95, 0.88, respectively. Conclusions: Serum IL-12, CDT, HGF and endotoxin have a trend of change in different stages of ALD, and IL-12 and CDT have high sensitivity and specificity for diagnosing ALD, and can be used as markers for early diagnosis of ALD. Serum HGF and endotoxin are valuable for assessing the severity of ALD.

Independence of carbohydrate-deficient isoforms of transferrin and cyclic citrullinated peptides in rheumatoid arthritis / Independência de isoformas de transferrina deficiente em carboidrato e peptídeos citrulinados cíclicos na artrite reumatoide

ABSTRACT Objective: The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides. Methods: The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method. Results: 80% of RA patients were positive for anti-CCP, 70% for RF and 62% for both, anti-CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti-CCP positive patients than that in anti-CCP negative. CDT (absolute and relative concentration) did not correlate with anti-CCP and RF. However, serum RF significantly correlated with anti-CCP. %CDT did not correlate with anti-CCP, but absolute level correlated with anti-CCP only in anti-CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti-CCP in anti-CCP negative patients. Anti-CCP correlated with DAS 28 only in anti-CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti-CCP positive RA. Conclusions: These results suggest that the changes in CDT and anti-CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA.

RESUMO Objetivo: Avaliar a relação entre os dois tipos de modificações pós-translacionais de proteínas na AR: glicosilação no caso da transferrina deficiente em carboidrato (TDC) e citrulinação por meio dos anticorpos no caso do antipeptídeo citrulinado cíclico (anti-CCP). Métodos: O estudo foi feito em 50 pacientes com AR. A TDC foi medida com o teste imunonefelométrico N Latex CDT e os resultados foram apresentados em unidades absolutas e relativas. O anti-CCP foi mensurado com o método quimioluminescente e o fator reumatoide (FR) pelo método imunoturbidimétrico. Resultados: Dos pacientes com AR, 80% foram positivos para anti-CCP, 70% para FR e 62% para ambos (anti-CCP e FR). A percentagem de transferrina total (%TDC) esteve significativamente elevada, mas o nível absoluto de TDC não esteve alterado. A concentração média de TDC absoluta foi maior nos pacientes anti-CCP positivos do que naqueles anti-CCP negativos. A TDC (concentração absoluta e relativa) não se correlacionou com o anti-CCP e o FR. No entanto, o FR sérico se correlacionou significativamente com o anti-CCP. O percentual de TDC não se correlacionou com o anti-CCP, mas seu nível absoluto se correlacionou com o anti-CCP apenas em pacientes FR negativos e anti-CCP negativos. A TDC não se correlacionou com o FR, somente com o anti-CCP em pacientes anti-CCP negativos. O anti-CCP se correlacionou com o DAS 28 apenas nos pacientes com AR anti-CCP negativos, mas a TDC (unidades absolutas e relativas) se correlacionou com o DAS 28 quando considerados todos os pacientes com AR e em pacientes com AR anti-CCP positivos. Conclusões: Esses resultados sugerem que as alterações na TDC e as concentrações de anti-CCP não estão associadas e indicam a independência dessas modificações pós-translacionais na artrite reumatoide. Apenas as alterações na glicosilação da transferrina refletem a atividade da AR.

The Alteration of % Carbohydrate-Deficient Transferrin and Gamma-Glutamyl Transferase Levels of Alcohol-Dependent Inpatients according to Age and Sex

OBJECTIVES: This study sought to investigate the relationship between age, sex and alterations in levels of % carbohydrate-deficient transferrin (%CDT) and gamma-glutamyl transferase (GGT) in patients admitted with alcohol dependence. METHODS: The study retrospectively enrolled 187 patients who were diagnosed with alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth edition (DSM-IV) and were admitted into a closed ward in Hallym University Hangang Sacred Heart Hospital from 2009 to 2012 and Hallym University Kangnam Sacred Heart Hospital from 2012 to 2017. Demographic factors (age, sex) and biochemical markers [%CDT, GGT, mean corpuscular volume (MCV), aspartate transferase (AST), alanine transferase (ALT)] were collected by reviewing medical records. Alterations in the levels of %CDT and GGT in different groups for each demographic factor were compared after correcting for confounding variables (age, initial %CDT, GGT, MCV, AST, ALT). RESULTS: Decreased %CDT and GGT were observed during the period of abstinence after admission. The normalization period for %CDT increased with age, while the normalization period for GGT was longer in female patients. CONCLUSIONS: These results suggest that alcohol-dependent patients that vary in age have different alterations in %CDT, while different sexes have different alterations in GGT. Age and sex can be potential indicators of treatment response after abstinence in patients with alcohol dependence. Further studies are needed to evaluate the relationship between these factors with regards to physiological and hematological changes in alcohol dependence.

The Alteration of Carbohydrate-Deficient Transferrin and Nerve Growth Factor in the Patients with Alcohol Dependence

OBJECTIVES: Recent studies have raised the possibility that nerve growth factor(NGF) is abnormally regulated in the central nervous system(CNS) of animal models with alcohol dependence. The possible alteration of NGF by prolonged alcohol intake may play an important role in alcohol-induced neurotoxicity. Carbohydrate-deficient transferrin(CDT) is regarded as a reliable biological marker of alcohol dependence. The goal of this study was to estimate the changes of %CDT and serum NGF level according to the duration of alcohol abstinence, and to identify whether %CDT level is associated with the serum NGF level in the patients with alcohol dependence. METHODS: The subjects were 24 patients with alcohol dependence. We used the Axis-Shield ASA to measure the %CDT level and the enzyme-linked immunosorbent assay(ELISA) to measure the serum NGF level. %CDT and NGF levels were measured immediately after the admission and at 2 weeks after the admission. RESULTS: Decreased %CDT were observed during the period of 2 weeks after the admission. NGF level was not significantly different after 2 weeks. The NGF levels were not correlated with %CDT. The possibility of %CDT as a predictor of alcohol-induced neurotoxicity was not confirmed. CONCLUSION: Serum NGF levels is not a reliable indicator of abstinence state in the patients with alcohol dependence. Further studies are needed to evaluate the relation between two indicators in regard to hematological and neurological changes in alcohol dependence.

Carbohydrate-deficient Transferrin as a Marker of Heavy Drinking in Korean Males

This study was performed to evaluate the usefulness of carbohydrate-deficient transferrin (CDT) as a marker of heavy drinking in Korean males. The subjects (143 Korean males) were classified into 2 groups according to the amount of drinking, moderate drinkers (72 individuals) who drank 14 drinks or less per week and heavy drinkers (71 individuals) who drank more than 14 drinks per week. Using %CDT, gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) as clinical markers for heavy drinking, sensitivity, specificity, positive and negative predictive values were investigated. Sensitivities of %CDT, GGT, AST, and ALT were 83.1%, 67.6%, 52.1% and 46.5%, respectively. Specificities were 63.9%, 45.8%, 72.2%, and 54.2%, respectively. Positive predictive values were 69.4%, 55.2%, 64.9%, and 50.0% respectively. Negative predictive values were 79.3%, 58.9%, 60.5%, and 50.6% respectively. The areas under the receiver operating characteristic curve (95% confidence interval) for %CDT, GGT, AST, and ALT were 0.823 (0.755-0.891), 0.578 (0.484-0.673), 0.622 (0.528-0.717), and 0.516 (0.420-0.613), respectively. CDT is considered as the most reliable marker for detecting heavy drinking in Korean males.

Comparing Biological Markers of Alcohol Dependence in the Patients of an Alcohol Counseling Center

OBJECTIVES: Biochemical markers can provide an objective evidence of heavy alcohol drinking. The purpose of this study was to compare and evaluate the usefulness of biological markers detecting alcohol dependence, such as mean corpuscular volume(MCV), gamma-glutamyl transferase(GGT), and carbohydrate-deficient transferrin(CDT) in the patients of an alcohol counseling center. METHODS: This study was done with 64 patients with alcohol dependence and 36 healthy subjects. Relative values(%) of CDT were determined in their sera with turbidimetric immunoassay(Bio-Rad %CDT assay, Axis-Shield ASA, Oslo, Norway), and were compared with conventional markers of alcohol consumption, GGT and MCV. RESULTS: Among the patients with alcohol dependence, 78.1% showed abnormal %CDT levels compared with GGT(61.9%) and MCV(20.7%). The areas under the receiver operating characteristic(ROC) curves(95% confidence interval) for %CDT, GGT, and MCV were 0.934(0.866-0.973), 0.871(0.789-0.930), and 0.575 (0.472-0.673), respectively. CONCLUSION: %CDT seems to be the most reliable biological marker for the detection and monitoring of alcohol consumption in the patients with alcohol dependence of the alcohol counseling center.

Diagnostic Utility of Carbohydrate-deficient Transferrin as a Marker of Alcohol Dependence / 대한진단검사의학회지

BACKGROUND: Biochemical markers can provide objective evidence of heavy alcohol drinking. In this study, we investigated the diagnostic usefulness of carbohydrate-deficient transferrin (CDT), a relatively new marker of alcohol consumption. METHODS: We consecutively enrolled 81 participants aged between 28 and 69 years, consisting of 44 alcohol-dependent patients and 37 age-matched controls. Relative values (%) of CDT were determined in their sera with turbidimetric immunoassay (Bio-Rad %CDT assay, Axis-Shield ASA, Oslo, Norway), and were compared with two conventional markers of alcohol consumption, gammaglutamyl transferase (GGT) and mean corpuscular volume (MCV). RESULTS: The distribution patterns of %CDT among alcohol-dependent patients and controls were significantly different from each other (P=0.0000). Of the 44 alcohol-dependent patients, positive results of %CDT (> or =2.6%), GGT (>50 IU/L), and MCV (>98 fL) were observed in 43 (97.7%), 35 (79.5%), and 24 (54.5%) patients, respectively. The areas under the receiver operating characteristic (ROC) curves (95% confidence interval) for %CDT, GGT, and MCV were 0.995 (0.946-1.000), 0.894 (0.805-0.951), and 0.768 (0.661-0.855), respectively. Discrimination between alcohol-dependent patients and controls, as measured by the areas under the ROC curves, was significantly better for %CDT than for GGT and MCV (P=0.000 and P=0.006, respectively). CONCLUSIONS: CDT seems to be the most reliable of the three markers tested for chronic alcohol consumption, and it may provide a useful information to for the objective detection of alcohol-dependent patients.

Serum Level of Carbohydrate Deficient Transferrin and Genetic Polymorphisms of Cytochrome P4502E1 in Patients with Alcoholism / 대한진단검사의학회지

BACKGROUND: The purpose of this study was to investigate genetic polymorphisms of cytochrome P4502E1 (CYP2E1) among healthy control and alcoholic Koreans in order to determine its relation-ship to the development of alcoholism. We also evaluate the diagnostic usefulness of carbohydrate deficient transferrin (CDT) in alcoholism. METHODS: The healthy control group included 72 males and 32 females. Patients with alcoholism included 53 males and 12 females who met DSM-IV diagnostic criteria (American Psychiatric Asso-ciation, 1994) and were admitted to alcoholism treatment units. Rsa I and Pst I restriction fragment length polymorphisms of CYP2E1 gene PCR product determined the genotype of CYP2E1. The serum level of CDT was analyzed by Behring Nephelometer II using %CDT turbidimetric immunoassay kit. RESULTS: The prevalence of CYP2E1 genotypes was 74.0% for type A, 23.1% for type B, and 2.9% for type C in the 104 healthy subjects, and 93.8% for type A and 6.2% for tyupe B in the 65 patients with alcoholism. The allele frequency of c1 and c2 of CYP2E1 was 85.6% and 14.4%, respectively, in the control group and 96.9% and 3.1%, respectively, in the alcoholics. The %CDT range in healthy controls and alcoholics was 0-7.8% and 3.1-21.1%, respectively. The serum CDT level in the patients with alcoholism (14.4 +/-4.5, mean +/-SD) was higher than that of healthy controls (3.2 +/-1.2, ) (P<0.05). The sensitivity, specificity, positive predictive value, negative predictive value, false positive rate, false negative rate, and test efficiency of %CDT were 85.1%, 93.3%, 88.7%, 90.6%, 6.7%, 15.4%, and 89.9%, respectively. CONCLUSIONS: There was a significant difference in frequencies of CYP2E1 genotype (P=0.001) and allele (P=0.003) between patient with alcoholism and control group, and the absence of CYP2E1 c2 allele was associated with alcoholism. Assessment of CDT yielded useful and objective informa-tion in the diagnosis and identification of alcoholism.