Phosphatidylethanol (PEth) for Monitoring Sobriety in Liver Transplant Candidates: Preliminary Results of Differences Between Alcohol-Related and Non-Alcohol-Related Cirrhosis Candidates.

BACKGROUND Monitoring sobriety is mandatory for liver transplant (LT) candidates with alcohol-related cirrhosis in Germany. Prior to listing, abstinence of 6 months is required. However, little is known about biomarker performance in alcohol-related cirrhosis. Routine testing of ethyl glucuronide in urine (uEtG) or hair (hEtG) is prone to manipulation or is unfeasible in anuria. Phosphatidylethanol (PEth) in dried-blood spots is a promising alternative. We compared PEth with routine parameters and self-reports in alcohol-related and non-alcohol-related cirrhosis at our transplant center. MATERIAL AND METHODS All patients received self-report questionnaires (AUDIT & TLFB). Blood, urine and hair samples, as well as PEth dried-blood spots were drawn at baseline. In addition, survival analyses were conducted. RESULTS Out of 66 patients, 53 were listed for LT and 13 were candidates not listed so far. An alcohol-use disorder was found in 25 patients. Positive results for uEtG, hEtG, and PEth were found in 5/65, 9/65, and 34/66 cases, respectively. PEth positivity was found in 52% of patients with alcohol-related cirrhosis, while 53% of patients with other liver diseases were positive. While uEtG, hEtG, and TLFB correlated with higher PEth values, active waiting list status was significantly correlated with negative PEth values. During the mean follow-up of 41.15 months, 23 patients were transplanted (34.9%). None of the biomarkers significantly predicted survival. CONCLUSIONS PEth can importantly assist abstinence monitoring in LT candidates due to its high validity and objectivity. The high percentage of patients with alcohol consumption in the non-alcoholic liver disease cohort underscores the importance of testing all transplant candidates.

Ethyl glucuronide in hair detects a high rate of harmful alcohol consumption in presumed non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) cannot reliably be distinguished by routine diagnostics, and the role of alcohol consumption in metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. We investigated alcohol consumption in patients with presumed NAFLD and ALD using novel objective alcohol markers. METHODS: In total, 184 consecutive patients were included in this prospective observational study. Alcohol intake was assessed by ethylglucuronide in hair (hEtG) and urine (uEtG); the utility of these measures for alcohol detection was compared to Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), carbohydrate deficient transferrin (CDT), mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT), and ALD/NAFLD index (ANI). Clinical characteristics of patients with NAFLD and ALD were re-assessed after reclassification based on repeated moderate (≥10 g <60 g EtOH/day) and excessive (≥60 g EtOH/day) alcohol consumption, and patients were retrospectively reclassified based on MAFLD criteria. RESULTS: Repeated moderate to excessive alcohol consumption was detected in 28.6%, 28.5%, and 25.0% of patients with presumed NAFLD, ALD or MAFLD, respectively. ANI score, AUDIT-C, uEtG, and hEtG showed AUCs of 0.628, 0.733, 0.754, and 0.927 for the detection of repeated moderate to excessive alcohol consumption, respectively. The indirect markers CDT, MCV and GGT were not reliable. Patients with repeated moderate or excessive alcohol consumption were significantly more often male, had a significantly lower BMI, and suffered significantly less often from type 2 diabetes or impaired glucose tolerance. CONCLUSIONS: In total, 28.6% of patients with presumed NAFLD, and 25.0% with MAFLD are at risk of alcohol-related liver damage. AUDIT-C, uEtG and hEtG should be used to screen for alcohol consumption in patients with fatty liver disease. LAY SUMMARY: Fatty liver disease can be caused by metabolic factors and/or alcohol consumption. The diagnosis of non-alcoholic fatty liver disease (NAFLD) is based on the exclusion of harmful alcohol consumption, while metabolic dysfunction-associated fatty liver disease (MAFLD), which has been proposed as a new name for NAFLD, is based on the presence of metabolic comorbidities and allows for alcohol consumption. Herein, we show that up to 29% of patients diagnosed with NAFLD and 25% with MAFLD are at risk of alcohol-related liver damage. We show that ethyl glucuronide (a metabolite of alcohol) in the hair and urine can accurately detect potentially harmful alcohol consumption in these patients - as such, these tests should be integrated into routine diagnostic work-up for patients with fatty liver disease.

Evaluation of decontamination procedures for drug testing in undamaged versus damaged hair.

Although substances incorporated by ingestion are strongly bound to hair, their loss may occur if aggressive decontamination procedures are applied, especially in highly damaged/porous hair. Evaluation of cleaning procedures using hair samples with different porosity obtained from ethanol or drug users (cocaine, heroin, methamphetamine, methadone, fentanyl, tramadol, diazepam, buprenorphine, dihydrocodeine, citalopram and trazodone). The effect of washing time and multiple wash steps with water and methanol were evaluated. Hair samples (n = 16) were selected and evaluated according to (a) the drug pattern consumption, (b) available amount, and (c) hair porosity (c1 'cosmetic treatment', c2: storage time). Six of them were soaked with an aqueous deuterated analogue solution. The samples were cut in 1-cm segments and homogenized. All hair samples were then decontaminated one or six times with 1.5 ml of water or methanol during 1, 5, 15, 30, 60 and/or 90 min (n = 1 to 3/sample, depending on the available amount of hair). Hair extracts were then cleaned up via a solid-phase extraction (SPE) or liquid-liquid extraction (LLE), while the washes were evaporated to dryness. All were thereafter reconstituted and analysed with routine ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods. Although concentrations of parent drugs and/or metabolites presented a negative trend along the washing time with methanol (up to 80%), the compounds were relatively well retained in hair even after a 90 min wash (with methanol or water) in most samples, and their retention would depend mostly on the hair nature rather than their physicochemical properties (whether incorporated by ingestion and/or from external contamination). Moreover, parent drugs and/or metabolites were detected in the washes in most samples, and the ratio between hair and washes decreased along the washing time. More than 50% of the deuterated analogues soaked into hair were still present after the different washing steps. Losses were observed more frequently for long-term stored hair samples, after decontamination with methanol for more than 30 min. Therefore, prolonged or repeated cleaning with methanol should be avoided in general procedures.

Two Cases of Fatal Inhalation of Easily Available "Recreational" Substances.

ABSTRACT: We present 2 cases of fatal inhalation of easily available highly volatile substances that occurred in a recreational context. Case 1 concerns an 18-year-old man who was found dead with a 25-L plastic bag pulled over his head and a whipped cream steel siphon connected to the bag. The deceased was known to previously have inhaled nitrous oxide. Autopsy results were unremarkable, toxicological analysis using static headspace gas chromatography coupled to mass spectrometry analysis proved the presence of nitrous oxide in lung tissue and blood. Asphyxiation was ascertained as the cause of death. Case 2 describes the death of a 54-year-old man found dead on his bed wearing a rubber gas mask. A bottle with ethyl chloride-containing cold spray was found beside him. Autopsy did not reveal relevant pathological findings; a subsequent toxicological analysis proved the presence of ethyl chloride. Respiratory arrest because of ethyl chloride inhalation was established as the cause of death. The 2 cases presented here demonstrate the danger of easily available, volatile substances with a high potential for abuse. A careful investigation of the death scene, proper specimen collection during the autopsy, and extensive toxicological tests, including headspace gas chromatography coupled to mass spectrometry analysis, are necessary to prove inhalation of these substances.

Phosphatidylethanol for Monitoring Alcohol Use in Liver Transplant Candidates: An Observational Study.

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.

AEME production in cocaine positive hair after thermal hair treatment.

INTRODUCTION: Currently, hair straightening has become a regular hair treatment for women but likewise for men. Several studies have shown that thermal straightening has an influence on the concentration of ethyl glucuronide and of drugs of abuse content in hair. Heat treatment of hair may decrease concentrations of cocaine (COC) and of cocaethylene (CE) in hair and increase concentrations of benzoylecgonine (BZE). The goal of this study was to evaluate the influence of thermal straightening on anhydroecgonine methyl ester (AEME), a known cocaine smoking marker, in hair. METHOD: 42 positive COC hair samples were treated in vitro with iron plates heated to 200°C. During this treatment one lock of hair was put sequentially 30 times in contact with a hair straightener during 2s, the other lock was not treated. The hair samples were analyzed by a validated GC/MS method for AEME, COC and its metabolites BZE, norcocaine (NC), ecgonine methyl ester (EME) and CE. RESULTS: After treatment, a median increase of concentrations was observed for AEME (110.3%) and BZE (27.6%) whereas a median decrease was found for COC (56.9%), NC (46.7%), EME (33.3%) and CE (41.7%). The median BZE/COC ratio of 0.6 in not treated hair increased to 1.5 in treated hair. CONCLUSION: Regarding our in vitro results, AEME may be produced by thermal hair straightening. Therefore, the presence of AEME in hair should not be used as an irrefutable prove of cocaine smoking. Our study shows that for the interpretation of AEME results in hair, potential heat treatment of hair should be considered. A ratio BZE/COC higher 1 appears to be a good marker to identify thermal treatment of hair before collection. Finally, thermal straightening should be documented during hair collection and should also be considered for the interpretation of COC results in hair.

Influence of cosmetic hair treatments on cannabinoids in hair: Bleaching, perming and permanent coloring.

Various cosmetic hair manipulations are known to interfere with drug of abuse concentrations in hair. It is important to evaluate the effects of cosmetic hair treatments as they can influence quantitative hair results. Only one study showed a significant decrease of THC after bleaching and coloring. The aim of the study was to investigate the effect of bleaching, perming and dyeing treatment on d-9-tetrahydrocannabinol (THC), but also Cannabidiol (CBD), Cannabinol (CBN) and 11-nor-D9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in hair. Thirty THC-positive hair samples were selected in this study. A single hair lock was divided in 2 separate locks and the proximal 3 cm segment was analyzed. One lock served as control while the other lock was bleached, permed or dyed respectively. Hair was analyzed using a routine method including cleaning, treatment of hair with NaOH and 2 different SPE extractions for THC, CBN, CBD and THC-COOH respectively. Analysis was performed with routine methods using GC/MS-MS in electron impact (EI) mode for THC, CBN and CBD or negative chemical ionization (NCI) mode for THC-COOH after PTV-injection. Bleaching and perming reduced all cannabinoids concentration in hair; THC was more affected than THC-COOH, CBN and CBD. Bleaching caused strong chemical degradation on cannabinoids, while perming exerted more a leaching out effect. Permanent colorings in single applications had only little effects on cannabinoids. Finally this study highlights the importance of considering bleaching and perming for the correct interpretation of hair results.

How to Interpret Hair EtG Concentrations in Individuals with High Body Mass Index? Brief Commentary on: Influence of Body Mass Index on Hair Ethyl Glucuronide Concentrations.

Body mass index (BMI) is a variable that complicates the interpretation of the alcohol metabolite ethyl glucuronide (EtG) in hair. However, direction on how EtG should currently be interpreted within individuals consuming moderate and excessive daily amounts of alcohol related to their BMI is lacking. In light of interpretation of EtG in individuals with high BMI, we present post hoc analysis of earlier data regarding the effect of BMI on hair EtG concentrations.

Determination of cannabinoids in hair of CBD rich extracts consumers using gas chromatography with tandem mass spectrometry (GC/MS-MS).

Medical cannabis is becoming increasingly popular for many different ailments and improvement of general well-being. Particularly CBD-rich extracts are easily available via online pharmacies, health stores or directly from producers. However, almost all of the extracts contain small amounts of THC. Thus, in case of continuous or heavy use of CBD rich cannabis, THC concentrations in hair may rise above accepted legal limits. In our study, we investigated THC, CBN and CBD in hair samples from regular CBD rich cannabis users. The goals were to determine levels of the cannabinoids in hair and to evaluate a possible correlation between regular CBD intake and CBD levels in hair. All participants consumed cannabis extracts from the same producer. It contained CBD at different concentrations and small amounts of THC with a CBD/THC concentration ratio of 30. The self-declared CBD dosage ranged from 4 to 128mg CBD/day, corresponding to a daily THC intake of 0.1 to 4.3mg. After extraction and derivatization, hair samples were analysed using a validated GC/MS-MS method. CBD concentrations ranged from 10 to 325pg/mg of hair, but no significant correlation was observed between CBD concentrations and the daily dose. THC was detected in one sample only at a concentration below our cut-off, whereas CBN was not detected. In this study, we showed that even after repeated consumption of CBD-rich cannabis extracts in medium to high doses, consumers are generally tested negative for THC in hair.

Gammahydroxybutyrate in hair of non-GHB and repeated GHB users: A new and optimized method.

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid used recreationally as a drug of abuse due its strong suppressive effect on the central nervous system. The detection window of GHB in blood and urine is very narrow (t1/2=30min) but can be substantially prolonged using alternative matrices such as hair. We here present a newly developed and limited validated method with a solid phase extraction (SPE) using GC-MS/MS to determine concentrations of GHB in hair samples. The soft extraction technique (water and 90min ultrasonic bath) preserves GHB with a high yield and clean extracts. In addition, endogenous GHB can be detected in hair of non-GHB users. However, little is known about GHB concentrations in hair of abstinent, frequent and chronic GHB users. Therefore, we present data from hair samples of healthy volunteers to evaluate the proposed endogenous GHB ranges, and from GHB-dependent patients to address GHB concentrations in hair with GHB intake. In 20 non-GHB users, a mean endogenous concentration of 1.1±0.6ng/mg hair (range of 0.3-2ng/mg) was found. In GHB-dependent patients, concentrations between 6.3-239.6ng/mg hair were found, with no correlation between concentrations in hair and dose of GHB intake. In summary, we present a new and limited validated method, adequately sensitive for the detection of GHB in hair, as well as first-time measurements of GHB concentrations in dependent patients in order to better understand the relationship between the frequency of use/dose and concentrations observed in hair samples.

Screening for Hazardous Drinking in Nursing Home Residents: Evaluating the Validity of the Current Cutoffs of the Alcohol Use Disorder Identification Test-Consumption Questions by Using Ethyl Glucuronide in Hair.

BACKGROUND: Because of physiological changes, elderly people are much more exposed to the adverse effects of alcohol. Therefore, hazardous drinking is defined at lower levels as compared to younger adults. This work aimed to evaluate the validity of the current cutoff levels of the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) questions to detect hazardous drinking in the elderly by using ethyl glucuronide in hair (HEtG). METHODS: In a border region between Austria and Germany, 344 nursing home residents were included from 33 of the 107 nursing homes. Residents were asked to answer the AUDIT-C questions, hair samples were obtained, and nursing staff members were asked for their assessments of the residents' alcohol consumption. Hair samples were analyzed for HEtG using gas chromatography-mass spectrometry. Receiver-operating characteristic (ROC) curve analysis was performed to determine the validity of cutoff values for the AUDIT-C to detect an alcohol consumption of ≥10 g of alcohol/d. RESULTS: A total of 11.3% of the nursing home residents (n = 344) drank ≥10 g of alcohol/d (4.9% >60 g of alcohol/d, 6.4% 10 to 60 g of alcohol/d, 88.7% <10 g of alcohol/d)). For the drinking limit of ≥10 g of alcohol/d, ROC curve analysis showed a balanced sensitivity and specificity, with an AUDIT-C cutoff of ≥4 for men (sensitivity: 70%, specificity: 83.6%; AUC = 0.823, CI = 0.718 to 0.928, p < 0.001) and ≥2 for women (sensitivity: 73.7%, specificity: 81.9%; AUC = 0.783, CI = 0.653 to 0.914, p < 0.001). Nursing staff (n = 274) underestimated alcohol consumption and evaluated 40% of the chronic-excessive alcohol consumers (>60 g of alcohol/d) as being abstinent. CONCLUSIONS: Our data suggest that an AUDIT-C cutoff of ≥4 for men and ≥2 for women can be recommended to detect the consumption of ≥10 g of alcohol/d in the elderly. Because the nursing staff to a large extent underestimates the alcohol consumption among nursing home residents, further teaching of the staff, improvement of screening instruments for the elderly, and the use of objective biomarkers might be helpful for recognizing hazardous drinking and can thus help improve the quality of life of the elderly.

Influence of Body Mass Index on Hair Ethyl Glucuronide Concentrations.

AIM: Analysis of ethyl glucuronide (EtG) concentrations in hair is increasingly used to estimate the consumption of alcohol of the prior months. Linear correlations between the amount of alcohol consumed and the concentration of EtG in hair have been reported, and several variables that may influence this correlation have been investigated: e.g. cosmetic hair treatments, gender influences or hair color. Here, we investigate the influence of body mass index (BMI) on this correlation. METHODS: A post hoc analysis on the influence of BMI on the relation between amounts of alcohol consumed and the measured EtG concentrations in hair in 199 participants. RESULTS: Our data show higher EtG concentrations in participants with high BMI (≥25) compared to participants with low BMI (<25) (P = 0.001) across a wide range of amounts of alcohol consumed. CONCLUSIONS: We conclude that BMI should be taken into account when interpreting hair EtG concentrations. SHORT SUMMARY: Ethyl glucuronide concentrations in hair (hEtG) can be used to estimate the consumption of alcohol of the prior months. Body mass index (BMI) influences this relation and BMI should be taken into account when interpreting hEtG concentrations in participants with high BMI (≥25) compared to participants with low BMI (<25).

Hair ethyl glucuronide concentrations in teetotalers: Should we re-evaluate the lower cut-off?

AIMS: Ethyl glucuronide in hair (hEtG) can be used to assess the retrospective consumption of alcohol. A lower cut-off of 7pg/mg hair in the 0-3cm proximal scalp hair segment has been used for repeated alcohol consumption in the previous three months. While a concentration below this cut-off is stated not to contradict self reported abstinence, it is often used to assess whether an individual has remained abstinent in the period prior to hair sampling. Here, we address hEtG concentrations in alcohol consuming individuals and critically evaluate this cut-off value. METHODS: Ten individuals remained abstinent from alcohol for 12 weeks. A lock of hair was cut before the start of the study, and the regrown hairs were cut after twelve weeks of abstinence. Hair EtG concentrations were measured both at baseline and after 12 weeks of abstinence. Study compliance was assessed by urine analysis every 2-3 days by liquid chromatography-tandem mass spectrometry with a lower limit of quantification (LLOQ) of 0.1µg/mL. HEtG concentrations were assessed in the first 3cm hair using gas chromatography-tandem mass spectrometry with an LLOQ of 0.2pg/mg. RESULTS: At the beginning of the study, participants had hEtG concentrations ranging between

Biomarkers for detection of alcohol consumption in liver transplantation.

Alcoholic liver disease is an established, yet controversial, indication for liver transplantation. Although an abstinence period of up to 6 mo prior to transplantation is mandatory, alcohol relapse after transplantation is a common event. In case of recurrence of heavy drinking, graft survival is significantly impaired. Guidelines on detection and surveillance of alcohol consumption in this patient cohort are lacking. This review summarizes the challenge of patient selection as well as the current knowledge on established and novel alcohol biomarkers with special focus on liver transplant candidates and recipients.

Hair ethyl glucuronide and serum carbohydrate deficient transferrin for the assessment of relapse in alcohol-dependent patients.

OBJECTIVES: Ethyl glucuronide in hair (hEtG) and serum carbohydrate deficient transferrin (%CDT) are valuable markers for alcohol abuse, but their diagnostic accuracy to monitor abstinence and relapse is unclear. Here, we investigate to what extent repeated measurements of hEtG and %CDT can be used to monitor relapse in alcohol-dependent patients during abstinence treatment. DESIGN AND METHODS: HEtG and %CDT were measured in individuals starting treatment for alcohol dependence both at treatment entry and 3months later. Alcohol consumption and relapse episodes were recorded using the Time Line Follow Back and by alcohol breath and urine tests, and correlated with hEtG and %CDT measurements. RESULTS: Fifteen patients completed the study, of which nine had one or more relapses. Hair EtG and serum %CDT identified whether a relapse occurred in 78% and 57% of cases, respectively. Only hEtG correlated with the amount of alcohol consumed before treatment entry (Pearson r=0.92; p<0.001). The specificity of %CDT to assess abstinence during treatment was 100%. HEtG had a specificity of only 17%; however, in all patients who remained abstinent, hEtG decreased with >85% from initial values. Mean hEtG, but not %CDT, differed significantly between patients who relapsed and patients who remained abstinent (p=0.034). CONCLUSIONS: HEtG was more sensitive than serum %CDT to assess relapse in alcohol-dependent patients and was positively correlated with the amounts of alcohol consumed. In contrast, serum %CDT was more specific for assessing abstinence. We highlight the benefit of repeated measurements of hEtG and serum %CDT for monitoring abstinence during treatment.

Influence of thermal hair straightening on cannabis and cocaine content in hair.

It has been shown that cosmetic treatment like bleaching and perming may lead to an important decrease of drugs of abuse content in hair. Currently, hair straightening has become a regular hair treatment especially for women. The aim of this preliminary study was to investigate the effect of in vitro treatment of hair with heat straightener on cannabis and cocaine concentrations in hair. 17 positive cannabis and 7 positive cocaine hair samples were treated in vitro with a hair straightener. During this treatment hair was put sequentially 30 times in contact with heated iron plates at 200°C during 2s corresponding to a total time of contact of 1min. THC and Cannabinol (CBN) were analysed in cannabis positive hair and cocaine, benzoylecgonin (BZE) and cocaethylene were analysed in cocaine positive hair. Analyses were performed with routine methods using GC/MS in electron impact mode. Regarding cannabis results a decrease of THC concentrations was found in 11 of 17 hair samples after thermal treatment, whereas in 6 cases an increase was shown. In all the hair samples CBN concentrations was explicitly higher after the in vitro treatment. Regarding cocaine results cocaine and cocaethylene concentrations decreased after treatment in all seven hair samples; in contrast, higher concentrations of BZE were determined. The strong increase of CBN and BZE content in hair after thermal treatments may be due to the fact that THC is converted by heat into CBN and cocaine into BZE, thus changing the respective ratios of the analysed substances. In conclusion, thermal straightening should be considered as other cosmetic hair treatments for a correct interpretation of hair results.

Ethyl glucuronide concentrations in hair: a controlled alcohol-dosing study in healthy volunteers.

Ethyl glucuronide (EtG) is a minor phase II metabolite of alcohol that accumulates in hair. It has been established as a sensitive marker to assess the retrospective consumption of alcohol over recent months using a cut-off of ≥7 pg/mg hair to assess repeated alcohol consumption. The primary aim was to assess whether amounts of alcohol consumed correlated with EtG concentrations in hair. Additionally, we investigated whether the current applied cut-off value of 7 pg/mg hair was adequate to assess the regular consumption of low-to-moderate amounts of alcohol. A prospective controlled alcohol-dosing study in 30 healthy individuals matched on age and gender. Individuals were instructed to drink no alcohol (N = 10), 100 g alcohol per week (N = 10) or 150 g alcohol per week (N = 10) for 12 consecutive weeks, before and after which hair was collected. Throughout the study, compliance to daily alcohol consumption was assessed by analyzing urine EtG three times weekly. Participants in the non-drinking group had median EtG concentrations of 0.5 pg/mg hair (interquartile range (IQR) 1.7 pg/mg; range < 0.21-4.5 pg/mg). Participants consuming 100 and 150 g alcohol per week showed median EtG concentrations of 5.6 pg/mg hair (IQR 4.7 pg/mg; range 2.0-9.8 pg/mg) and 11.3 pg/mg hair (IQR 5.0 pg/mg; range 7.7-38.9 pg/mg), respectively. Hair EtG concentrations between the three study groups differed significantly from one another (p < 0.001). Hair EtG concentrations can be used to differentiate between repeated (low-to-moderate) amounts of alcohol consumed over a long time period. For the assessment of repeated alcohol use, we propose that the current cut-off of 7 pg/mg could be re-evaluated.

Ethanol metabolites: their role in the assessment of alcohol intake.

BACKGROUND: Alcohol-related disorders are common, expensive in their course, and often underdiagnosed. To facilitate early diagnosis and therapy of alcohol-related disorders and to prevent later complications, questionnaires and biomarkers are useful. METHODS: Indirect state markers like gamma-glutamyl-transpeptidase, mean corpuscular volume, and carbohydrate deficient transferrin are influenced by age, gender, various substances, and nonalcohol-related illnesses, and do not cover the entire timeline for alcohol consumption. Ethanol (EtOH) metabolites, such as ethyl glucuronide, ethyl sulfate, phosphatidylethanol, and fatty acid ethyl esters have gained enormous interest in the last decades as they are detectable after EtOH intake. RESULTS: For each biomarker, pharmacological characteristics, detection methods in different body tissues, sensitivity/specificity values, cutoff values, time frames of detection, and general limitations are presented. Another focus of the review is the use of the markers in special clinical and forensic samples. CONCLUSIONS: Depending on the biological material used for analysis, ethanol metabolites can be applied in different settings such as assessment of alcohol intake, screening, prevention, diagnosis, and therapy of alcohol use disorders.