Carbohydrate-Deficient Transferrin is a Sensitive Marker of Alcohol Consumption in Fatty Liver Disease

BackgroundThe prevalence of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated/related liver disease (ALD) with metabolic syndrome is globally increasing. Metabolic syndrome and excessive alcohol consumption synergically exacerbate liver pathologies; therefore, drinking-specific serum markers unaffected by liver injury or metabolic syndrome are essential to assess alcohol consumption. We evaluated the ratio of carbohydrate-deficient transferrin to total transferrin (%CDT) in patients with fatty liver disease, particularly focusing on its correlation with metabolic factors (UMIN000033550). MethodsA total of 120 patients with fatty liver disease, including ALD and NAFLD, were screened for alcohol misuse using the Alcohol Use Disorders Identification Test. Associations of metabolic syndrome-related factors and hepatic steatosis/liver stiffness with drinking markers such as %CDT, gamma-glutamyl transferase (GGT), and mean corpuscular volume (MCV) were assessed using multiple linear regression analyses. Results%CDT significantly increased with 3–4 drinks/day. The optimal cut-off value for identifying non- to light drinkers was 1.78% (sensitivity, 71.8%; specificity, 83.7%; area under the receiver operating characteristic curve [AUROC], 0.851), which was significantly higher than that for GGT. The cut-off value for identifying heavy drinkers was 2.08% (sensitivity, 65.5%; specificity, 86.8%; AUROC, 0.815). Multiple regression analysis revealed that this proportion was negatively correlated with body mass index, whereas GGT and MCV were influenced by multiple factors involved in liver injury and dyslipidemia. Conclusions%CDT showed a strong correlation with alcohol consumption, independent of liver damage, steatosis/stiffness, or metabolic syndrome-related factors, indicating that it is a useful drinking marker for the accurate diagnosis of NAFLD and ALD.

Clinical Significance of Gamma-Glutamyltranspeptidase Combined with Carbohydrate-Deficient Transferrin for the Assessment of Excessive Alcohol Consumption in Patients with Alcoholic Cirrhosis

: Background: This study aimed to compare the diagnostic performance of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltranspeptidase (γ-GTP) to assess the single and combined benefits of these biological markers for the detection of chronic excessive alcohol consumption in patients with alcoholic cirrhosis. Methods: Biological markers were determined in blood samples from patients with alcoholic cirrhosis (drinking group, n = 35; nondrinking group, n = 81). The prediction accuracy of %CDT alone, γ-GTP alone, and their combination for the detection of excessive alcohol consumption was determined in patients with alcoholic cirrhosis. Results: Serum total bilirubin, alanine aminotransferase, aspartate aminotransferase, γ-GTP, and alkaline phosphatase levels and %CDT were significantly higher and serum albumin levels were significantly lower in the drinking group than in the nondrinking group. The combination of %CDT and γ-GTP compared with %CDT or γ-GTP alone showed a higher prediction accuracy. The combination of %CDT and γ-GTP exhibited a higher specificity than γ-GTP alone. However, in terms of sensitivity, no significant difference was found between single or combined markers. Conclusions: The combination of %CDT and γ-GTP is considered a useful biomarker of chronic excessive alcohol consumption in patients with alcoholic cirrhosis.

Methodological approaches to identifying markers of alcohol abuse in employees according to medical examination

Introduction. The diagnosis and appointment of adequate therapy for both alcohol dependence syndrome and somatic pathology of alcoholic origin often depends on the timely establishment of the fact of alcohol abuse, for example, during periodic medical examinations, since most patients either deny the use of alcohol, or significantly underestimate its amount. The aim of the study is to develop a methodology for the objective identification of individuals with risk factors for harmful alcohol consumption that contribute to the development of pathological conditions and diseases that increase the likelihood of developing chronic non-communicable diseases. Materials and methods. Within the framework of the study, 204 people (162 men, 42 women) working in various types of economic activities, aged from 18 to 65 years, were surveyed. All patients were sent to the clinic FSBSI "Izmerov Research Institute of Occupational Health" to pre-or periodic inspections in the order of the health Ministry of Russia from 12.04.2011 No. 302n (ed. by 18.05.2020). All the examined patients underwent a biochemical blood test: carbohydrate deficient transferrin (CDT), gamma-glutamyltranspeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT). Also, all the surveyed were conducted a questionnaire aimed at identifying alcoholism. Statistical processing of the obtained results was carried out using the program STATISTICA 13.2 (Stat Soft Inc., USA). Results. The study of the CDT content in the blood serum of the examined patients revealed an increase above the reference values in 10%, while 7% of the examined patients regularly consumed alcohol during the last 2 weeks (CDT≥2.5%), 3% - consumed moderately (CDT1,2-2,4%). The correlation analysis showed a moderate positive correlation between the results of the questionnaire and the CDT content in the blood serum (r=0.24, p=0.002 with the question about the use of 6 or more doses at a time and r=0.30, p=0.0001 with the total score). Conclusion. The most informative marker of chronic alcohol use is the definition of CDT in combination with a questionnaire aimed at identifying alcoholism. The use of these markers during periodic and preliminary medical examinations can allow a high degree of confidence to identify persons who are prone to chronic alcohol consumption in order to carry out preventive measures and prevent them from working with various sources of increased danger, including work related to the management of vehicles.

Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study

A recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study’s conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin. We have likewise observed improvements in transferrin glycosylation without mannose supplementation. This observation questions the reliability of transferrin as a therapeutic outcome measure in clinical trials for PMM2-CDG. We are concerned that renewed focus on mannose therapy in PMM2-CDG will detract from clinical trials of more promising therapies. Approaches to increase efficiency of clinical trials and ultimately improve patients’ lives requires prospective natural history studies and identification of reliable biomarkers linked to clinical outcomes in CDG. Collaborations with patients and families are essential to identifying meaningful study outcomes.