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Two years ago, many experts spoke out in favour of changing the nomenclature of the most common liver disease in the world, non-alcoholic fatty liver disease (NAFLD) (1). This was the subject of an editorial in the Acta Gastroenterologica Belgica Journal (1). Even though many researchers still mention that its pathophysiology remains poorly understood or that the exact mechanisms remain to be elucidated, it would be dishonest not to recognise a common factor, namely the metabolic context (metabolic syndrome, insulin resistance and possibly type 2 diabetes, overweight or obesity) in the pathogenesis of this liver disease (1). The term “MAFLD” for “metabolic dysfunction-associated fatty liver disease” therefore makes sense. It is indeed more logical to call something by what it is than by what it is not (1). The perceived stigma of patients using the term “alcoholic” in naming their disease also supports an adaptation of the nomenclature (2).

OBJECTIVES: Alcohol biomarkers are used to detect alcohol exposure in clinical and forensic settings. This includes professional health program (PHP) monitoring of healthcare workers in recovery from substance use disorders. Here we present the case of a physician whose positive alcohol biomarker test result was complicated by a traumatic stress response to frontline work during COVID-19. METHODS: An anesthesiologist under PHP monitoring for substance use disorder and depression was interviewed extensively, urine and blood biomarkers were obtained, and longitudinal structured and semi-structured interviews related to anxiety, depression, posttraumatic stress, and cravings were used to monitor responses to the unanticipated death of a patient who succumbed to COVID-19. RESULTS: After an initial positive ethylglucuronide (EtG) and ethylsulfate (EtS) toxicology test result, all subsequent testing was negative. Standardized assessments and clinical interviews provided documentation of a post-traumatic stress reaction. The physician described compulsive sanitizing of hands/arms and mask with highly concentrated ethanol-based products. CONCLUSIONS: Inhalation of ethanol vapors is a possible explanation for the initial positive EtG/EtS results. To our knowledge, this case represents the highest reported levels of EtG/EtS likely due to workplace exposure. The importance of rapid intervention to thoroughly assess positive toxicology testing and its source(s) cannot be overstated, particularly as it relates to frontline healthcare workers during the pandemic. The PHP monitoring process provides an opportunity to promptly detect healthcare workers in distress, allowing for efficient connection to supportive resources and/or treatment when indicated, and possibly preventing escalation of symptoms or disease recurrence.

BACKGROUND: Alcohol consumption is a frequently studied risk factor for chronic diseases, but many studies are hampered by self-report of alcohol consumption. The urinary metabolite ethyl glucuronide (EtG), reflecting alcohol consumption during the past 72 h, is a promising objective marker, but population data are lacking. OBJECTIVE: The objective of this study was to assess the reliability of EtG as a marker for habitual alcohol consumption compared with self-report and other biomarkers in the general population. METHODS: Among 6211 participants in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort, EtG concentrations were measured in 24-h urine samples. EtG was considered positive when concentrations were ≥100 ng/mL. Habitual alcohol consumption was self-reported by questionnaire (categories: no/almost never, 1-4 units per month, 2-7 units per week, 1-3 units per day or ≥4 units per day). Plasma HDL cholesterol concentration, erythrocyte mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltransferase (GGT) were determined as indirect biomarkers of alcohol consumption. Sensitivity, specificity, positive and negative predictive value, and proportions of agreement between reported consumption and EtG were calculated. To test the agreement of EtG concentration and alcohol consumption in categories, linear regression analysis was performed. In addition, the association between EtG concentrations and indirect biomarkers was analyzed. RESULTS: Mean age was 53.7 y, and 52.9% of participants men. Of the self-reported abstainers, 92.3% had an EtG concentration

Background LC–MS/MS allows for many measurands monitoring different mass transitions simultaneously. So far, such alternative mass transitions are usually assessed as “quantifier and qualifier ions” in order to rule out interferences in individual samples. However, quantification can also be based on assessment of alternative mass transitions for both the measurand and its internal standard, with two distinct results for one injection of an individual sample. These paired results can be averaged. The aim of this study was to determine the potential impact of this averaging approach on measurement imprecision. Methods We studied the impact of averaging results from different transitions for four exemplary measurands (linezolid (LIN), piperacillin (PIP), voriconazole (VOR), ethylglucuronide (ETG)). Intra-batch studies were performed with 21 injections of single clinical samples in sequence for each analyte (LIN, PIP, VOR), and a between-batch study with evaluation of data from routine QC samples from 20 series over 20 weeks (ETG). CVs and their confidence intervals were assessed comparatively for quantification based on single transitions, and for averaged results from these two transitions, respectively. Results In all data sets, we observed lower CVs for the averaged results compared to the results obtained from single mass transitions. CVs from averaged results were up to 39.4% lower compared to the CVs observed for results obtained from single transitions for the respective measurands. Conclusion Averaging of quantification results obtained from separate mass transitions acquired simultaneously in ID-LC-MS/MS seems to have the potential to minimize the measurement imprecision for different measurands in short- and long-term settings.

International audience; Ethanol is the most frequently psychoactive substance used in the world, leading to major public health problems with several millions of deaths attributed to alcohol consumption each year. Metabolism of ethanol occurs mainly in the liver via the predominant oxidative metabolism pathway involving phase I enzymes including alcohol dehydrogenases (ADH), cytochrome P450 (CYP) 2E1 and catalase. In a lesser extent, an alternative non-oxidative pathway also contributes to the metabolism of ethanol, which involves the uridine diphospho-glucuronosyltransferase (UGT) and sulfotransferase (SULT) phase II enzymes. Using liquid chromatography-high resolution mass spectrometry, ethylglucuronide (EtG) and ethylsulfate (EtS) produced respectively by UGT and SULT conjugation and detected in various biological samples are direct markers of alcohol consumption. We report herein the efficient non-oxidative metabolic pathway of ethanol in human differentiated HepaRG cells compared to primary human hepatocytes (HH). We showed dose- and time-dependent production of EtS and EtG after ethanol (25 or 50 mM) treatment in culture media of differentiated HepaRG cells and HH and a significant induction of CYP2E1 mRNA expression upon acute ethanol exposure in HepaRG cells. These differentiated hepatoma cells thus represent a suitable in vitro human liver cell model to explore ethanol metabolism and more particularly EtG and EtS production. In addition, using recombinant HepG2 cells expressing different UGT1A genes, we found that UGT1A9 was the major UGT involved in ethanol glucuronidation.

Liver transplantation remains an essential procedure for many patients suffering from alcoholic liver disease. Alcohol use monitoring remains paramount all through the stages of this complex process. Direct alcohol biomarkers, with improved specificity and sensibility, should replace traditional indirect markers. Phosphatidylethanol (PEth) has been recently tested in alcoholic liver disease patients, but more evidence is needed, especially in comparison with other direct biomarkers. We conducted an observational study among patients awaiting liver transplantation. We analyzed Peth in blood, ethylglucuronide (EtG) in hair and urine and ethylsulphate (EtS) in urine, using mass spectrometry methods. In addition, transaminases, and self-reports were analyzed. A total of 50 patients were included (84% men, mean age 59 years (SD = 6)). 18 patients (36%) screened positive for any marker. Self-reports were positive in 3 patients. EtS was the biomarker with more positive screens. It also was the most frequently exclusive biomarker, screening positive in 7 patients who were negative for all other biomarkers. PEth was positive in 5 patients, being the only positive biomarker in 2 patients. It showed a false negative in a patient admitting alcohol use the previous week and screening positive for EtG and EtS. Hair EtG was positive in 3 patients who had negative Peth, EtG. EtG did not provide any exclusive positive result.A combination of biomarkers seems to be the best option to fully ascertain abstinence in this population. Our study suggest EtS might also play a significant role.

This article aims to place the phosphatidylethanol (PEth) blood test in the detection area of ethanol consumption causing alcohol-related disorders, to present the current methods of analysis, data on interpretation, some practical applications and the prospects of use of this biomarker. PEth is a minor metabolite of ethanol. Among nearly 50 PEth counterparts, PEth 16:0/18:1 is the most abundant. The interest that PEth brings compared to other biomarkers is the extended window of detection of ethanol consumptions. Indeed, it has a blood elimination half-life of approximately 5 days, which offers estimated alcohol consumption for a 21 to 28 days period. Thus, the detection of alcohol use disorders and withdrawal monitoring (systematically combined with urinary ethylglucuronide) in addictology and in liver pre- and post-transplantation are today its main routine applications. Nevertheless, additional data are still necessary to improve the interpretation of measured concentrations and to reach a consensus on interpretation cut-offs of blood PEth concentrations.

De alcoholkater wordt gedefinieerd als de combinatie van mentale en fysieke symptomen die ervaren worden de dag na een stevige drinksessie, die start wanneer de bloedalcoholconcentratie de nulwaarde nadert. Dit artikel betreft een naturalistisch opgezet onderzoek naar de samenhang tussen de ernst van de alcoholkater en mogelijke biomarkers voor een alcoholkater, namelijk de urineconcentraties van ethanol, methanol, ethylglucuronide (EtG) en ethylsulfaat (EtS). Aan dit onderzoek deden 36 gezonde sociale drinkers mee (18 katersensitieve en 18 katerresistente drinkers). Van alle deelnemers werden op een postalcoholdag en op de controledag de urineconcentraties van ethanol, methanol, EtG en EtS bepaald. Deelnemers konden zelf hun controledag en postalcoholdag bepalen, evenals de hoeveelheid alcohol die zij consumeerden. Vervolgens is de correlatie tussen de urineconcentratie en de ernst van de alcoholkater berekend en gescoord op een schaal van 0 (afwezig) tot 10 (extreem erg). De correlatie tussen de ernst van de alcoholkater en de urineconcentraties waren niet significant. Wel correleerden de ethanol-urineconcentraties significant met de ernst van de alcoholkater. Verder onderzoek is nodig naar de pathologie van de alcoholkater en mogelijke biomarkers die significant correleren met de ernst van de kater.

To evaluate adherence to treatment, we developed and validated a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for baclofen quantification in hair.Twenty mg was washed twice with dichloromethane, incubated in phosphate buffer (pH 5) for 10 minutes at 95°C, then extracted by liquid-liquid extraction in alkaline condition. Baclofen-d4 was used as the internal standard. This method was applied to assess compliance in4 treated alcohol-dependent patients (3 dead and one living). Blood quantification of baclofen and ethanol were performed in the 4 cases. Hair ethylglucuronide (ethanol metabolite, EtG) measurement (2x3 cm) was associated in 1 patient. Baclofen quantification in hair was validated over the range 10-5000 pg/mg. The accuracy was within 96.0%-110.9% and the precision was less than 9.3%. Baclofen segmental (3x2cm) hair concentrations found in the living patient were 4420, 4260, and 4380 pg/mg, reflecting a regular exposure over the last 6 months and suggesting patient compliance. However, the high EtG level found in this patient in the analyzed segments (225 pg/mg and 215 pg/mg) showed excessive alcohol consumption during the same period, suggesting therapeutic failure. In the 3 deceased patients, the non-segmental analysis of hair showed baclofen concentrations of 15, 545, and 2475 pg/mg. The low concentrations in the 2 first cases are compatible either with a poor compliance or to a beginning of a treatment. This is the first measurement of baclofen in hair of alcohol dependent patients. It could be used as a monitoring biomarker to assess patient's compliance.

Ethyl glucuronide (EtG) is an ethanol metabolite and EtG is used as a biomarker of alcohol drinking. EtG can be detected in the blood and in several biological matrices including urine, hair and nails. Alcohol consumption during pregnancy is a strong risk factor for fetus health so in the recent years different strategies to reveal alcohol use have been planning including the use of screening questionnaires as the AUDIT-C, T-ACE and TWEAK. The present study aims to investigate in pregnant women the specificity and predictive value of the AUDIT-C, T-ACE and TWEAK plus a food diary in use in Sapienza University Hospital compared with the results of urine EtG measurement. Seventy pregnant women were enrolled and examined. Urine samples were provided by pregnant women immediately after the interviews. EtG determinations were performed by Enzyme Immunoassay with a cut-off established at 100 ng/mL. Data show that 34.28% of the enrolled pregnant women overcame the EtG cut off. No direct correlation was found between EtG data and the alcohol screening interviews showing lower levels of alcohol consumption, although T-ACE revealed the same at risk percentage. However, a significant concordance was observed with food diary data and T-ACE only in patients with higher EtG urinary concentration. This study provides clinical evidence that the diagnosis of maternal alcohol consumption during pregnancy only based on indirect methods, such as questionnaires and food diary, may significantly underestimate alcohol use.

Fetal alcohol spectrum disorders (FASDs) are a group of negative conditions occurring in children exposed to alcohol during gestation. The early discovery of FASD is crucial for mother and infant follow-ups. In this study, we investigated in pregnant women the association between urine ethylglucuronide (EtG-a biomarker of alcohol drinking) and indicators of the physical characteristics of FASD by prenatal ultrasound in the second trimester of gestation. We also correlated these data with the AUDIT-C, T-ACE/TACER-3, TWEAK, and food habit diary, screening questionnaires used to disclose alcohol drinking during pregnancy. Forty-four pregnant women were randomly enrolled and examined for ultrasound investigation during the second trimester of gestation. Urine samples were provided by pregnant women immediately after the routine interviews. EtG determinations were performed with a cutoff established at 100 ng/mL, a value indicating occasional alcohol drinking. Fifteen of the enrolled pregnant women overcame the EtG cutoff (34.09%). Analysis of variance (ANOVA) revealed that the fetuses of the positive EtG pregnant women had significantly longer interorbital distance and also significantly increased frontothalamic distance (P's < 0.02). Quite interestingly, no direct correlation was found between EtG data and both food diary and AUDIT-C. However, a significant correlation was observed between urinary EtG and T-ACE (r = 0.375; P = 0.012) and between urinary EtG and TWEAK (r = 0.512; P < 0.001) and a concordance with all questionnaire for EtG values higher than 500 ng/mL. This study provides clinical evidence that the diagnosis of maternal alcohol consumption during pregnancy by urine EtG may disclose FASD-related damage in the fetus.

Background Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease (CVD) and all‐cause mortality compared with heavy drinkers and abstainers. To date, studies have relied on self‐reported consumption, which may be prone to misclassification. Urinary ethyl glucuronide (EtG) is an alcohol metabolite and validated biomarker for recent alcohol consumption. We aimed to examine and compare the associations of self‐reported alcohol consumption and EtG with CVD and all‐cause mortality. Methods and Results In 5676 participants of the PREVEND (Prevention of Renal and Vascular End‐Stage Disease) study cohort, EtG was measured in 24‐hour urine samples and alcohol consumption questionnaires were administered. Participants were followed up for occurrence of first CVD and all‐cause mortality. Cox proportional hazards regression models, adjusted for age, sex, and CVD risk factors, were fitted for self‐reported consumption, divided into 5 categories: abstention, 1 to 4 units/month (reference), 2 to 7 units/week, 1 to 3 units/day, and ≥4 units/day. Similar models were fitted for EtG, analyzed as both continuous and categorical variables. Follow‐up times differed for CVD (8 years; 385 CVD events) and all‐cause mortality (14 years; 724 deaths). For both self‐reported alcohol consumption and EtG, nonsignificant trends were found toward J‐shaped associations between alcohol consumption and CVD, with higher risk in the lowest (hazard ratio for abstention versus 1–4 units/month, 1.42; 95% CI, 1.02–1.98) and highest drinking categories (hazard ratio for ≥4 units/day versus 1–4 units/month, 1.11; 95% CI, 0.68–1.84). Neither self‐report nor EtG was associated with all‐cause mortality. Conclusions Comparable associations with CVD events and all‐cause mortality were found for self‐report and EtG. This argues for the validity of self‐reported alcohol consumption in epidemiologic research.

De alcoholkater wordt gedefinieerd als de combinatie van mentale en fysieke symptomen die ervaren worden de dag na een stevige drinksessie, die start wanneer de bloedalcoholconcentratie de nulwaarde nadert. Dit artikel betreft een naturalistisch opgezet onderzoek naar de samenhang tussen de ernst van de alcoholkater en mogelijke biomarkers voor een alcoholkater, namelijk de urineconcentraties van ethanol, methanol, ethylglucuronide (EtG) en ethylsulfaat (EtS). Aan dit onderzoek deden 36 gezonde sociale drinkers mee (18 katersensitieve en 18 katerresistente drinkers). Van alle deelnemers werden op een postalcoholdag en op de controledag de urineconcentraties van ethanol, methanol, EtG en EtS bepaald. Deelnemers konden zelf hun controledag en postalcoholdag bepalen, evenals de hoeveelheid alcohol die zij consumeerden. Vervolgens is de correlatie tussen de urineconcentratie en de ernst van de alcoholkater berekend en gescoord op een schaal van 0 (afwezig) tot 10 (extreem erg). De correlatie tussen de ernst van de alcoholkater en de urineconcentraties waren niet significant. Wel correleerden de ethanol-urineconcentraties significant met de ernst van de alcoholkater. Verder onderzoek is nodig naar de pathologie van de alcoholkater en mogelijke biomarkers die significant correleren met de ernst van de kater.

De alcoholkater wordt gedefinieerd als de combinatie van mentale en fysieke symptomen die ervaren worden de dag na een stevige drinksessie, die start wanneer de bloedalcoholconcentratie de nulwaarde nadert. Dit artikel betreft een naturalistisch opgezet onderzoek naar de samenhang tussen de ernst van de alcoholkater en mogelijke biomarkers voor een alcoholkater, namelijk de urineconcentraties van ethanol, methanol, ethylglucuronide (EtG) en ethylsulfaat (EtS). Aan dit onderzoek deden 36 gezonde sociale drinkers mee (18 katersensitieve en 18 katerresistente drinkers). Van alle deelnemers werden op een postalcoholdag en op de controledag de urineconcentraties van ethanol, methanol, EtG en EtS bepaald. Deelnemers konden zelf hun controledag en postalcoholdag bepalen, evenals de hoeveelheid alcohol die zij consumeerden. Vervolgens is de correlatie tussen de urineconcentratie en de ernst van de alcoholkater berekend en gescoord op een schaal van 0 (afwezig) tot 10 (extreem erg). De correlatie tussen de ernst van de alcoholkater en de urineconcentraties waren niet significant. Wel correleerden de ethanol-urineconcentraties significant met de ernst van de alcoholkater. Verder onderzoek is nodig naar de pathologie van de alcoholkater en mogelijke biomarkers die significant correleren met de ernst van de kater.

ObjectiveTo investigate the feasibility of determining the pattern and prevalence of alcohol consumption in pregnancy by measuring ethanol biomarkers in meconium.DesignPopulation-based observational study.SettingInner-city maternity unit in Scotland, UK.PopulationRandom sample of singleton infants delivered after 36 completed weeks’ gestation.MethodsFatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG) in meconium were measured by liquid chromatography-mass spectroscopy. Samples were frozen at −20°C before analysis. Results were compared anonymously with demographic data including maternal age, parity, smoking, ethnicity and postcode and with infant gestation, birth weight and head circumference. Written informed consent was obtained from all subjects.Results235 samples of meconium were analysed (70% of eligible babies). Only four (1%) of mothers declined to participate. FAAEs were detected in all, including four samples below the limit of quantification (10 ng/g). 98 (42%) samples had FAEE concentrations >600 ng/g. EtG was detectable in 93 (40%) samples; in 35 (15%) EtG concentration was >30 ng/g. No mother reported heavy alcohol consumption in pregnancy. FAAE concentration correlated with EtG (Pearson’s coefficient; pConclusionMeasurement of ethanol biomarkers in meconium is a feasible tool for determining the pattern and prevalence of alcohol consumption in pregnancy. Data suggest that at least 15% of pregnant women in the west of Scotland are consuming significant quantities of alcohol during latter pregnancy.

Alcohol use disorder is a leading cause of preventable death with serious consequences in many domains. There is an increasing need to fine tune detection and diagnostic methods to enable health care workers prevent, diagnose and manage this disorder. The diagnosis of an alcohol problem could be quite a challenge as the disorder can present as other psychiatric syndromes. The diagnostic armamentarium includes good history and clinical examination, screening tools and biomarkers. Biomarkers are divided into direct and indirect physiologic biomarkers and two of these, namely EtG and EtS, are proving to be a great asset in guiding clinicians to determine alcohol consumption, retrospectively, over many days

Resume Dans le cadre d’une etude en milieu ambulatoire ayant pour objectif de montrer l’efficacite du baclofene sur la consommation d’alcool, il est propose lors de la visite de sortie de realiser le dosage de l’ethyl glucuronide (EtG) dans les urines. Les inclusions de cette etude etant multicentriques, le probleme de conservation des prelevements urinaires avant acheminement apparait comme une limite au dosage de ce marqueur. Nous avons donc envisage une etude de stabilite complete sur trois semaines chez differents types de consommateurs pour apprecier la faisabilite de ce dosage dans les conditions de cette etude. Les dosages urinaires lors d’une consommation controlee d’alcool chez deux temoins permettent egalement de decrire l’elimination urinaire de ce marqueur. Des urines de temoins consideres comme buveurs sociaux ou alcooliques chroniques sont recueillies le matin. Les dosages d’EtG (DRI, Thermo Fisher Scientific, seuil de positivite 0,5 mg/L), d’ethanol et de creatinine urinaires, ainsi qu’une analyse cytobacteriologique sont realises au moment du recueil. Le dosage d’EtG est teste sur des tubes contenant de l’acide borique et sur des flacons type ECBU sans conservateur. Dans un premier temps, on realise l’etude de stabilite pour chaque urine pendant 3 semaines dans des conditions differentes de temperature (4 °C, temperature ambiante), d’oxydation et de lumiere et pendant 3 mois a −20 °C. Puis, on etudie le suivi de l’elimination urinaire de l’EtG chez deux temoins apres consommation controlee de 10 et 30 g d’alcool. Les prelevements urinaires realises sur des tubes contenant de l’acide borique (pour eviter la proliferation bacterienne pouvant fausser le dosage de l’EtG) ont tous donne des resultats faussement negatifs. Les concentrations mesurees dans les flacons type ECBU varient de 0,50 a 17,83 mg/g de creatinine (entre H12 et H18) pour la categorie des « buveurs sociaux » ( n = 7) et beaucoup plus elevees de 88,32 et de 125,24 mg/g de creatinine pour deux « alcooliques chroniques ». L’etude menee sur une periode de trois semaines et l’etude de congelation sur trois mois montrent une excellente stabilite pour l’ensemble des conditions etudiees (CV entre 3,1 % et 13,9 %). Des concentrations mesurees a differents temps pour deux temoins pour des consommations controlees de 10 et 30 g d’alcool montrent des resultats tres variables. Les estimations de la surface sous la courbe des cinetiques d’elimination urinaire en fonction du temps, des demi-vies d’elimination (entre 2,75 et 3,50 h) permettent de realiser une approche de la fenetre de detection de l’EtG dans les urines (entre 12,1 h pour une dose de 10 g et 30,1 h pour une dose de 30 g). Les resultats sur les tubes contenant de l’acide borique ne sont pas utilisables. Pour l’etude en ambulatoire, nos resultats de stabilite montrent qu’il n’y a aucune precaution particuliere a prendre et que des pots sans conservateur peuvent etre utilises. Les variabilites observees pour les temoins dont l’EtG dans les urines a ete mesure pour differentes quantites d’alcool consomme, peuvent etre expliquees par une saturation des voies oxydatives principales de l’alcool (ADH) a l’origine d’une surexpression de la voie minoritaire de l’UDP-glucuronosyltransferase (UGT) pour laquelle on decrit un polymorphisme genetique.

The deleterious effects exerted by prenatal ethanol exposure include physical, mental, behavioral, and/or learning disabilities that are included in the term fetal alcohol spectrum disorder. The measurement of ethylglucuronide (EtG) in alternative biological matrices, including neonatal and maternal hair, neonatal meconium, and maternal nails, is receiving increasing interest for the accurate evaluation of the in utero exposure to alcohol.To evaluate the correlation between EtG in maternal hair and nails with EtG in neonatal meconium to further explore the suitability of these biomarkers in disclosing prenatal exposure to ethanol.A total of 151 maternal hair strands (0-6 cm), nail clips (2-6 mm), and corresponding neonatal meconium and nails samples were obtained from neonatal wards of 4 Mediterranean public hospitals: Rome, Florence, and Belluno in Italy and Barcelona in Spain. Hair, nails, and meconium were analyzed for the presence of EtG by validated liquid chromatography mass spectrometry assay. Meconium was also analyzed for the presence of fatty acid ethyl esters (FAEEs) as a complementary biomarker of potential in utero exposure to alcohol.Eighteen newborns resulted in utero exposed to maternal alcohol consumption by FAEE testing in meconium with EtG values between 0.5 and 1.5 nmol/g. Unfortunately, none of these cases were confirmed by the presence of EtG in maternal hair and nails samples, which resulted all negative to this biomarker.The results confirm that FAEEs and EtG in meconium are the best biomarkers to assess in utero exposure to maternal alcohol. EtG in hair and nails are not good biomarkers to disclose alcohol consumption lower than on daily basis and lower than 1-2 alcoholic units per day.

Ethylglucuronide (EtG) is a biomarker of ethanol consumption, and the authors propose an overview of its potential use in clinical or forensic cases. This metabolite presents a higher half-life and is therefore detectable longer than ethanol itself, and allows, in the case of late sampling, the research of acute alcohol abuse in the days prior to urine sampling. Routine testing for urinary EtG can be easily introduced in laboratories since an immunochemical kit is available. However, it is necessary to take into account the cut-off values in order to interpret the results. EtG can also be tested in hair and is a very useful biomarker of chronic alcohol abuse. A recent international consensus has established cut-off values for the interpretation of EtG concentrations in hair. However, hair testing is still limited to specific laboratories as it is not easily implemented in routine, due to a specific sample treatment and to the lack of immunochemical kits.

The quantification of ethylglucuronide (EtG) in hair is nowadays recognized as the approach with the highest diagnostic performance to evaluate harmful drinking. A widely accepted cut-off of 30pg/mg has been selected after several accurate compared studies. While most of the studies that were used to establish the appropriate cut-off value prescribed to cut hair into small segments before their extraction, hair milling has subsequently been identified as the most efficient pretreatment procedure and was therefore recommended in the last Consensus document issued by the Society of Hair Testing. In this study, we initially compared the results obtained with the two sample preparations, namely cutting and milling, both being applied to the same specimens ( n =781). Among these, 205 samples produced measurable EtG values with both methods, with differences ranging from ⿿41.7% up to +415% (the mean increase in EtG concentration, switching from cutting to milling, was +62.1% and the median was +42.3%). Among the aforementioned 205 samples, 29 specimens (3.7% of the total 781 samples) produced significantly different outcome, being classified as negative (i.e., below 30pg/mg) if the cutting procedure is used, but largely positive (above 40pg/mg) when milling is used. Subsequently, the positivity rates obtained on a large population dataset (>27,000 samples) with the two procedures, were retrospectively compared using variable cut-offs values. The percentage of head hair samples with EtG concentration exceeding 30pg/mg upon application of the milling procedure shows a 45% increase (from 10.9% to 15.8%) with respect to cutting procedure, whereas the fraction of hair samples with EtG exceeding 40pg/mg (10.5%) overlaps the percentage of positive samples obtained after cutting pretreatment and applying a cut-off of 30pg/mg. On the basis of these results, it would be worth considering the application of cut-off values linked with the pretreatment procedure, taking into account the results of forthcoming inter-laboratory calibrations.

Ethanol is the most frequently psychoactive substance used in France, leading to major public health pro-blems. Alcohol intake detection might be important in a variety of clinical and forensic settings. Interestin-gly, ethylglucuronide (EtG) and ethylsulfate (EtS) are potentially direct markers of alcohol consumption, being detected in various biological samples such as blood, urine or hair. Moreover, since their detection timeframe corresponds to few hours until several days, these two biomarkers can prove ethanol intake even after the complete elimination of alcohol from the body. We describe herein the metabolic pathway of ethanol leading to EtG and EtS production, the currently used methods for their determination, the precautions in data interpretation and clinical applications of the measurement of these two biomarkers of alcohol misuse., L’éthanol est la substance psychoactive la plus consommée en France et pose de réel problème de santé publique. La mise en évidence de sa consommation par des méthodes biologiques peut s’avérer importante aussi bien dans des contextes cliniques que dans des affaires médico-judiciaires. L’éthylglucuronide (EtG) et l’éthylsulfate (EtS) sont des marqueurs directs d’une consommation d’éthanol pouvant être identifiables dans différentes matrices biologiques comme le sang, l’urine ou les cheveux, ce qui représente un intérêt majeur à leur utilisation. De plus, leur détection peut se faire plusieurs heures voire même plusieurs jours après ingestion, ce qui permet de mettre en évidence une consommation d’éthanol après que celui-ci ait disparu de l’organisme. Cet article présente de manière synthétique les voies de production de l’EtG et l’EtS lors du métabolisme de l’éthanol, les méthodes actuellement employées pour leur mise en évidence, ainsi que les précautions d’interprétation des résultats et les applications du dosage de ces marqueurs dans différents contextes.

In this issue, Jatlow and colleagues have provided the field with the report of a well done and timely scientific evaluation of one of the newer alcohol consumption biomarkers, urinary ethylglucuronide (EtG), and a related metabolite, ethylsulfate (EtS). These naturally occurring chemical conjugates between ethanol and glucuronide (EtG) or sulfate (EtS), while elegant in their simplicity, have caused a certain amount of discussion and controversy not only in the literature, but also in clinical practice (Center for Substance Abuse Treatment, 2012; Litten et al., 2010). EtG and EtS have been around for some time (Wurst et al., 2003), but highly structured investigations into their interpretation and utility have been few (Wurst et al., 2004, Hoiseth et. al., 2012). The concerns which have haunted both investigators and clinicians alike, and which have spilled over into forensic circles, involve cut-off levels, windows of detection of alcohol consumption, sensitivity and specificity of measurement, and the potential for use for monitoring abstinence in clinical practice and in clinical trials. In this paper, the authors have provided crucial information that increases the knowledge in most of these areas.

Many different biomarkers can be used to evaluate ethanol intake. Ethylglucuronide, a minor metabolite of ethanol, is a biomarker that is useful in determining ethanol intake up to 80 hours after ethanol consumption. To better understand the utility of this biomarker, a MEDLINE search of ethylglucuronide in the English-language literature from January 1987-August 2007 was performed; clinical trials and case reports were reviewed. In addition, relevant nonmedical media and government documents were reviewed. Ethylglucuronide has an extended window of detection compared with other biomarkers and can be detected in urine 1 hour after ethanol ingestion. However, incidental exposure to ethanol-containing products may cause false-positive results, and false-negative results have been reported when urine has been infected with certain bacteria that cause urinary tract infections. Before a urine sample is submitted for ethylglucuronide evaluation, a thorough drug history should be obtained. Misinterpretation of ethylglucuronide results can produce serious adverse medical and social consequences. When positive ethylglucuronide screen results are reported, further evaluation of the clinical picture and confirmation with ethylglucuronide quantification and self-report should be instituted. Clinicians should have a thorough understanding of the strengths and weaknesses of the ethylglucuronide test when used in various settings.

Two studies were performed to evaluate the effect of alcohol containing mouthwash on the appearance of ethyl glucuronide (EtG) in urine. In the first study, 9 volunteers were given a 4-oz bottle of mouthwash, which contained 12% ethanol. They gargled with all 4 oz. of the mouthwash at intervals over a 15-min period. All urine samples were collected over the next 24 h. Of 39 provided urine samples, there were 20 > 50 ng/mL, 12 > 100 ng/mL, 5 > 200 ng/mL, 3 > 250 ng/mL, and 1 > 300 ng/mL. The peak concentrations were all within 12 h after the exposure. In the second study, 11 participants gargled 3 times daily for 5 days. The first morning void was collected. Sixteen of the 55 submitted samples contained EtG concentrations of greater than 50 ng/mL. All of them were less than 120 ng/mL. These studies show that incidental exposure to mouthwash containing 12% ethanol, when gargling according to the manufacturer's instructions, can result in urinary EtG values greater than 50 ng/mL. All specimens were negative for ethanol. The limits of detection and quantitation for the EtG testing were 50 ng/mL.