Background: The Alcohol Use Disorders Identification Test (AUDIT) has been extensively researched to determine its capability to accurately and practically screen for alcohol problems.

Methods: During the 5 years since our previous review of the literature, a large number of additional studies have been published on the AUDIT, abbreviated versions of it, its psychometric properties, and the applicability of the AUDIT for a diverse array of populations. The current article summarizes new findings and integrates them with results of previous research. It also suggests some issues that we believe are particularly in need of further study.

Results: A growing body of research evidence supports the criterion validity of English version of the AUDIT as a screen for alcohol dependence as well as for less severe alcohol problems. Nevertheless, the cut-points for effective detection of hazardous drinking as well as identification of alcohol dependence or harmful use in women need to be lowered from the originally recommended value of 8 points. The AUDIT-C, the most popular short version of the AUDIT consisting solely of its 3 consumption items, is approximately equal in accuracy to the full AUDIT. Psychometric properties of the AUDIT, such as test–retest reliability and internal consistency, are quite favorable. Continued research is urged to establish the psychometric properties of non-English versions of the AUDIT, use of the AUDIT with adolescents and with older adults, and selective inclusion of alcohol biomarkers with the AUDIT in some instances.

Conclusions: Research continues to support use of the AUDIT as a means of screening for the spectrum of alcohol use disorders in various settings and with diverse populations.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1530-0277.2006.00295.x

The Alcohol Use Disorders Identification Test: An Update of Research Findings

The AUDIT Alcohol Consumption Questions (AUDIT-C) An Effective Brief Screening Test for Problem Drinking

Background: Efficient, inexpensive screening for early stage alcohol problems is important in health care settings. The Alcohol Use Disorders Identification Test (AUDIT) has been studied extensively to establish its value in this regard.

Methods: A literature search that used EtOH as a database was conducted to identify studies published on the AUDIT through September 2001. Keywords used for the search were “Alcohol Use Disorders Identification Test” and “AUDIT.” All studies reporting psychometric properties of the measure were reviewed with particular attention being given to the period 1996 and later. A small number of additional references were located by noting their citation in other studies reviewed.

Results: Although more research is needed on non-English versions to establish their psychometric properties, at least in its English edition, the AUDIT demonstrates sensitivities and specificities comparable, and typically superior, to those of other self-report screening measures. Test-retest reliability and internal consistency are also quite favorable. For males, the AUDIT-C, a shortened version of the AUDIT, appears approximately equal in validity to the full scale.

Conclusions: Recent research continues to support use of the AUDIT as a means of screening for alcohol use disorders in health care settings in the United States.

The Alcohol Use Disorders Identification Test (AUDIT): A Review of Recent Research

Serum gamma-glutamyl transferase (GGT) has been widely used as an index of liver dysfunction and marker of alcohol intake. The last few years have seen improvements in these areas and advances in understanding of its physiological role in counteracting oxidative stress by breaking down extracellular glutathione and making its component amino acids available to the cells. Conditions that increase serum GGT, such as obstructive liver disease, high alcohol consumption, and use of enzyme-inducing drugs, lead to increased free radical production and the threat of glutathione depletion. However, the products of the GGT reaction may themselves lead to increased free radical production, particularly in the presence of iron. There have also been important advances in the definition of the associations between serum GGT and risk of coronary heart disease, Type 2 diabetes, and stroke. People with high serum GGT have higher mortality, partly because of the association between GGT and other risk factors and partly because GGT is an independent predictor of risk. This review aims to summarize the knowledge about GGT's clinical applications, to present information on its physiological roles, consider the results of epidemiological studies, and assess how far these separate areas can be combined into an integrated view.

/pdf/gamma-glutamyl-transferase-g960wl2pzr.pdf

Gamma Glutamyl Transferase

Geigy Scientific Tables

Background: Estimates of the performance of carbohydrate deficient transferrin (CDT) and gamma glutamyltransferase (GGT) as markers of alcohol consumption have varied widely. Studies have differed in design and subject characteristics. The WHO/ISBRA Collaborative Study allows assessment and comparison of CDT, GGT, and aspartate aminotransferase (AST) as markers of drinking in a large, well-characterized, multicenter sample. Methods: A total of 1863 subjects were recruited from five countries (Australia, Brazil, Canada, Finland, and Japan). Recruitment was stratified by alcohol use, age, and sex. Demographic characteristics, alcohol consumption, and presence of ICD-10 dependence were recorded using an interview schedule based on the AUDADIS, CDT was assayed using CDTect(TM) and GGT and AST by standard methods. Statistical techniques included receiver operating characteristic (ROC) analysis. Multiple regression was used to measure the impact of factors other than alcohol on test performance. Results: CDT and GGT had comparable performance on ROC analysis, with AST performing slightly less well. CDT was a slightly but significantly better marker of high-risk consumption in men. All were more effective for detection of high-risk rather than intermediate-risk drinking. CDT and GGT levels were influenced by body mass index, sex, age, and smoking status. Conclusions: CDT was little better than GGT in detecting high- or intermediate-risk alcohol consumption in this large, multicenter, predominantly community-based sample. As the two tests are relatively independent of each other, their combination is likely to provide better performance than either test alone, Test interpretation should take account sex, age. and body mass index.

/pdf/cdt-ggt-and-ast-as-markers-of-alcohol-use-the-who-isbra-2r9gbv3gkm.pdf

CDT, GGT, and AST as markers of alcohol use: the WHO/ISBRA collaborative project.

Aims: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are conjugated ethanol metabolites formed in low amounts after alcohol consumption. Compared with ethanol, EtG and EtS are excreted in urine for a prolonged time, making them useful as sensitive alcohol biomarkers. This study determined the detection times for EtG and EtS in alcoholic patients undergoing alcohol detoxification. Methods: Alcohol-dependent patients ( n = 32) with an initial alcohol concentration ≥1 g/L based on breath testing were followed during detoxification. Urine samples for determination of EtG, EtS, ethanol and creatinine were collected on admission to the hospital and thereafter once daily for several days. EtG and EtS measurements were performed by liquid chromatography-mass spectrometry (LC-MS) and EtG also using an immunochemical assay (DRI-EtG EIA, ThermoFisher/Microgenics). Results: The detection time for urinary EtG was weakly correlated ( r = 0.434, P = 0.013) with the initial alcohol concentration (range 1.0–3.4 g/L). For EtG, the individual time range until return to below the applied cut-off limit (<0.5 mg/L) was ∼40–130 h (median 78) with a similar time course observed for EtS. After correction for urine dilution, the time until an EtG/creatinine ratio <0.5 mg/g was ∼40– 90 h (median 65). The detection times after an estimated zero ethanol concentration were ∼30–110 h (median 66) for EtG and ∼30– 70 h (median 56) for EtG/creatinine. The EtG results by LC-MS and the immunoassay were in good agreement. Conclusions: During alcohol detoxification, EtG and EtS remained detectable in urine for several days. The detection times showed wide inter-individual variations, also after adjusting values for urine dilution and to the estimated times for a completed ethanol elimination.

/pdf/detection-times-for-urinary-ethyl-glucuronide-and-ethyl-4fbtr9ew9t.pdf

Detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during alcohol detoxification.

This study compared the urinary excretion characteristics of ethyl glucuronide (EtG) with that of ethanol, with focus on the effect of water-induced diuresis. Six healthy volunteers ingested an ethanol dose of 0.5 g/kg (range 25.0-41.5 g) as 5% (v/v) beer in 30 min and the same volume of water after 3 h. Urine collections were made before starting the experiment and at timed intervals over 31.5 h. The concentration of EtG was determined by an LC-MS method (LOQ = 0.1 mg/L). The urine samples collected immediately before starting drinking were all negative for ethanol and EtG, thus confirming that the participants had not recently ingested alcohol. Intake of beer resulted in a marked increase in excreted urine volume and a concomitant drop in creatinine concentration. The concentration of ethanol peaked at a mean value of 17 mmol/L in the 1.5-h urine collection. Except for one subject, EtG was first detectable (range 0.9-5.5 mg/L) at 1 h. Intake of water at 3 h produced another increase in urine volume and a drop in creatinine. The ethanol concentration curve was not influenced by the water diuresis, whereas this caused a distinct drop in the EtG concentration. When EtG was expressed relative to the creatinine value, this ratio was seemingly not affected by the intake of water. The ethanol concentration returned to zero at 6.5 h, whereas EtG was still detectable for up to 22.5-31.5 h, albeit at low levels in the end (< 1 mg/l). Only about 0.02% of the administered dose of ethanol (on a molar basis) was recovered in the urine as EtG. The results demonstrated that EtG remains detectable in the urine for many hours after the ethanol itself has been eliminated. Moreover, it was possible to lower the concentration of EtG by drinking large amounts of water prior to voiding, whereas this strategy did not influence the EtG/creatinine ratio or the concentration of ethanol.

/pdf/comparison-of-urinary-excretion-characteristics-of-ethanol-2qll73ufis.pdf

Comparison of urinary excretion characteristics of ethanol and ethyl glucuronide.

Background: Isoforms of transferrin interfere with measurement of carbohydrate-deficient transferrin (CDT) as a marker of heavy alcohol consumption. We evaluated the rate of inaccurate CDT results by immunoassays.

Methods: We studied 2360 consecutive sera (1614 individuals) submitted for CDT assay without clinical information as well as samples from 1 patient with a congenital disorder of glycosylation (CDG Ia) and from 6 healthy carriers of CDG Ia. The CDTect, %CDT-TIA, and new %CDT immunoassays were compared with HPLC (%CDT-HPLC). Transferrin isoform pattern were evaluated by isoelectric focusing (IEF).

Results: Transferrin BC and CD heterozygotes were found at frequencies of ∼0.7% and ∼0.2%, respectively. Another transferrin C subtype, where di- and trisialotransferrin partly coeluted (tentatively identified as C2C3), was observed in ∼0.6%. Compared with the %CDT-HPLC method, the immunoassays often produced low results for transferrin BC and high results for transferrin CD and “C2C3”. A very high trisialotransferrin value (frequency ∼1%) often produced high CDT immunoassay results. In four of six healthy carriers of CDG Ia, a- and disialotransferrin were highly increased and the HPLC and IEF isoform patterns were indistinguishable from those in alcohol abuse.

Conclusions: Rare transferrin isoform types and abnormal amounts of trisialotransferrin (total frequency ∼2–3%) may cause incorrect determination of CDT with immunoassays. The observed variants were readily identified by HPLC and IEF, which can be recommended for verification of CDT immunoassay results in doubtful cases. In healthy carriers of CDG Ia, CDT is high by all assays.

/pdf/interference-of-transferrin-isoform-types-with-carbohydrate-2ucgpbohqb.pdf

Interference of Transferrin Isoform Types with Carbohydrate-deficient Transferrin Quantification in the Identification of Alcohol Abuse

Background: There is need for a reference method for transferrin glycoforms in serum to which routine immunologic methods for the alcohol marker carbohydrate-deficient transferrin (CDT) can be traceable. We describe an improved HPLC method for transferrin glycoforms.

Methods: Transferrin was iron-saturated by mixing the serum with ferric nitrilotriacetic acid, and lipoproteins were precipitated with dextran sulfate and calcium chloride. Separation of glycoforms was performed on a SOURCE 15Q anion-exchange column using salt gradient elution. Quantification relied on selective absorbance of the iron–transferrin complex at 470 nm. The relative amount of each glycoform was calculated as a percentage of the area under the curve, using baseline integration.

Results: The HPLC system provided reproducible separation and quantification of the asialo-, monosialo-, disialo-, trisialo-, tetrasialo-, pentasialo-, and hexasialotransferrin glycoforms. Most importantly, disialo- and trisialotransferrin were almost baseline separated. The intra- and interassay CV for disialotransferrin were 6%) trisialotransferrin, monosialotransferrin was detected at <0.25%. Asialotransferrin was not detected in control sera, but was detected in 57% of chronic heavy drinkers and in 62% of sera with ≥2% disialotransferrin.

Conclusions: The HPLC method fulfills the requirements of a preliminary reference method for CDT and should work for any combination of serum transferrin glycoforms. This method could also be useful for confirming positive CDT results by immunoassays in medico-legal cases.

/pdf/improved-hplc-method-for-carbohydrate-deficient-transferrin-vdcye4lm6e.pdf

Anders Helander

Papers

CDT, GGT, and AST as markers of alcohol use: the WHO/ISBRA collaborative project.

Detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during alcohol detoxification.

Comparison of urinary excretion characteristics of ethanol and ethyl glucuronide.

Interference of Transferrin Isoform Types with Carbohydrate-deficient Transferrin Quantification in the Identification of Alcohol Abuse

Improved HPLC Method for Carbohydrate-deficient Transferrin in Serum