Standardisation and use of the alcohol biomarker carbohydrate-deficient transferrin (CDT)

Helander, Anders; Wielders, Jos P.M.; Anton, Raymond F.; Arndt, T.; Bianchi, Vincenza; Deenmamode, Jean; Jeppsson, Jan‐Olof; Whitfield, John B.; Weykamp, Cas; Schellenberg, François

doi:10.1016/j.cca.2016.05.016

Cited by 47 publications

(26 citation statements)

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“…The measurement of disialotransferrin (%dCDT or DST) by HPLC is a well-validated test for chronic heavy alcohol consumption, and is the recommended reference assay (Helander et al, 2016). However, a proportion of subjects with severe liver disease will have uninterpretable HPLC results due to the presence of di-tri bridging.…”

Section: Discussionmentioning

confidence: 99%

“…Quantification of individual glycoforms is performed by monitoring the absorbance of the transferrin-iron complex at 470 nm (Shimadzu UV detector), with disialotransferrin quantified as the relative amount (% of total transferrin) based on peak areas. The International Federation of Clinical Chemistry (IFCC) recommends this HPLC assay as the current reference assay (Helander et al, 2016). The CNL is certified by the College of American Pathology and Clinical Laboratory Improvement Act, proficient with the HPLC assay and a member of the working group for standardization of CDT within the IFCC (Helander et al, 2010(Helander et al, , 2016.…”

Section: Methodsmentioning

confidence: 99%

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Relationship of Abnormal Chromatographic Pattern for Carbohydrate-Deficient Transferrin with Severe Liver Disease

Stewart

Reuben

Anton

2016

Alcohol and Alcoholism

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Aims: Serum carbohydrate-deficient transferrin (CDT) is a validated test for chronic heavy alcohol drinking, but CDT abnormalities have been associated with liver disease, limiting its use in these patients. We report here on the association between poor chromatographic resolution of disialotransferrin from trisialotransferrin (the so-called 'di-tri bridging') and liver disease severity and etiology. Methods: Subjects were patients in whom detailed clinical data, including histology results, were available on their existing liver diseases (n=139). Percent disialo-CDT (%dCDT) was measured by high-performance liquid chromatography, and the risks for di-tri bridging associated with cirrhosis, with and without adjustment for alcohol use and alcohol-related liver disease, were estimated. Results: Di-tri bridging was present in 22/73 (30%) cirrhotic subjects and 7/66 (11%) non-cirrhotic subjects. The unadjusted risk for di-tri bridging in cirrhotics relative to non-cirrhotics was 3.6 (95% confidence interval 1.4-9.2). Adjustment for alcohol-related liver disease and current drinking had little effect on this estimate (adjusted odds ratio 3.4), and neither alcohol-related liver disease nor current drinking were independently associated with di-tri bridging after accounting for the effect of cirrhosis. Conclusions: The presence of di-tri bridging was associated with cirrhosis in individuals with both alcohol-related and non-alcoholic liver disease, although most cirrhotic subjects did not exhibit di-tri bridging. When di-tri bridging is seen in individuals being tested for chronic heavy drinking, investigation for cirrhosis should be considered. Short summary: There are known liver-disease-associated abnormalities in CDT. In this study, we found that such abnormalities were strongly associated with cirrhosis rather than less-advanced disease, but were only clinically evident in 30% of cirrhotics. Abnormalities also occurred in severe hepatitis without cirrhosis and were not specific for liver disease etiology.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Relationship of Abnormal Chromatographic Pattern for Carbohydrate-Deficient Transferrin with Severe Liver Disease

Stewart

Reuben

Anton

2016

Alcohol and Alcoholism

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“…AUD individuals were also required to meet criteria for DSM-IV diagnostic criteria for alcohol dependence (including the "loss of control over drinking" and/or "inability to cut-down or stop drinking" criteria), to report consuming at least 20 total drinks per week, with at least one heavy drinking day (i.e., ≥ 5/4 drinks in a day for men/ women) per week, in each of the two weeks preceding the study, and to not be actively seeking AUD treatment. Light-drinking individuals were required to not meet DSM-IV diagnostic criteria for alcohol dependence, to report drinking fewer than 14 drinks (7 for women) in each of the two weeks preceding the study, and to have a negative result (i.e., ≤ 1.6 IU) for disialo carbohydrate-deficient transferrin (%dCDT), a biomarker for recent (past 2-week) heavy drinking (Helander et al, 2016). For both groups, exclusion criteria included current DSM-IV Axis I disorder other than alcohol dependence or nicotine dependence, positive urine drug or alcohol breath screens on the day of the scan, and/or history of severe alcohol withdrawal (seizure, delirium tremens, need for inpatient or outpatient detoxification), or current alcohol withdrawal symptoms (i.e., Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised [CIWA-Ar;(Sullivan et al, 1989)] > 3).…”

Section: Participantsmentioning

confidence: 99%

Brain Glutamate, GABA, and Glutamine Levels and Associations with Recent Drinking in Treatment‐Naïve Individuals with Alcohol Use Disorder Versus Light Drinkers

Prisciandaro

Schacht

Prescot

et al. 2019

Alcoholism Clin & Exp Res

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Background-Proton Magnetic Resonance Spectroscopy (1 H-MRS) studies have demonstrated abnormal levels of a variety of neurometabolites in inpatients/outpatients with Alcohol Use Disorder (AUD) following acute alcohol withdrawal relative to healthy controls. In contrast, few studies have compared neurometabolite levels between less severe, treatment-naïve AUD individuals and light drinkers or related them to recent alcohol consumption. The present study compared neurometabolite levels between treatment-naïve AUD and LD individuals. Methods-Twenty treatment-naïve individuals with AUD and 20 demographically-matched LD completed an 1 H-MRS scan, approximately 2.5 days following their last reported drink. 1 H-MRS data were acquired in dorsal anterior cingulate (dACC) using a Two-dimensional J-resolved Point Resolved Spectroscopy sequence. dACC neurometabolite levels, with a focus on glutamate, glutamine, and GABA, were compared between AUD and LD participants. Associations between metabolite levels and recent drinking were explored. Results-AUD participants had significantly lower concentrations of GABA (Cohen's D=0.79, p=0.017) and glutamine (Cohen's D=1.12, p=0.005), but not glutamate (Cohen's D=0.05, p=0.893), relative to LD. As reported in Prisciandaro et al. (2016), AUD participants' glutamate and NAA concentrations were inversely associated with their number of heavy drinking days. In contrast, neither number of drinking (mean p=0.56) nor heavy drinking (mean p=0.47) days were associated with metabolite concentrations in LD. Conclusions-The present study demonstrated significantly lower levels of prefrontal GABA and glutamine in treatment-naïve individuals with AUD relative to LD. Whether these findings reflect the neurotoxic consequence and/or neuroadaptive response of alcohol consumption versus a pre-drinking trait, and therefore a more durable neurochemical disturbance, awaits elucidation from longitudinal studies.

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“…Following excessive alcohol ingestion for extended time periods, the amounts of less glycosylated forms with pI values of 5.7 (disialo-Tf) and 5.9 (asialo-Tf) are increasing which results in elevated CDT values [1, [3][4][5][6][7][8][9][10][11][12]. The international working group of CDT standardization of the International Federation of Clinical Chemistry and Laboratory Medicine recommended that disialo-Tf should be the primary target molecule for CDT determination and the single analyte on which CDT standardization should be based [99][100][101][102][103]. Thus, selected control samples with elevated disialo-Tf levels do not contain asialo-Tf [104].…”

Section: Monitoring Of Cdtmentioning

confidence: 99%

Monitoring of transferrin isoforms in biological samples by capillary electrophoresis

Caslavska

Thormann

2017

J of Separation Science

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Work dealing with the monitoring of transferrin isoforms in human serum and other body fluids by capillary electrophoresis is reviewed. It comprises capillary zone electrophoresis and capillary isoelectric focusing efforts that led to the exploration and use of assays for the determination of carbohydrate‐deficient transferrin as a marker for excessive alcohol intake, genetic variants of transferrin, congenital disorders of glycosylation and β‐2‐transferrin, which is a marker for cerebrospinal fluid leakage. This paper provides insight into the development, specifications, strengths, weaknesses, and routine use of the currently known capillary electrophoresis based assays suitable to detect transferrin isoforms in body fluids. The achievements reached so far indicate that capillary zone electrophoresis is an attractive technology to monitor the molecular forms of transferrin in biological specimens as the assays do not require an elaborate sample pretreatment and thus can be fully automated for high‐throughput analyses on multicapillary instruments. Assays based on capillary isoelectric focusing are less attractive. They require immunoextraction of transferrin from the biological matrix and mobilization after focusing if instrumentation with a whole‐column imaging detector is not available. Interactions of the carrier ampholytes with the iron of transferrin may prevent iron saturation and thus provide more complicated isoform patterns.

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Standardisation and use of the alcohol biomarker carbohydrate-deficient transferrin (CDT)

Cited by 47 publications

References 62 publications

Relationship of Abnormal Chromatographic Pattern for Carbohydrate-Deficient Transferrin with Severe Liver Disease

Relationship of Abnormal Chromatographic Pattern for Carbohydrate-Deficient Transferrin with Severe Liver Disease

Brain Glutamate, GABA, and Glutamine Levels and Associations with Recent Drinking in Treatment‐Naïve Individuals with Alcohol Use Disorder Versus Light Drinkers

Monitoring of transferrin isoforms in biological samples by capillary electrophoresis

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