Elimination of matrix effects in urine for determination of ethyl glucuronide by liquid chromatography-tandem mass spectrometry.

RATIONALE: Alcohol use disorder affects 4% to 5% of the world's population. Analysis methods are available for various biological fluids to detect this disorder. Determination of ethyl glucuronide in urine by the liquid chromatography-tandem mass spectrometry (LC/MS/MS) method is frequently used in forensic toxicology. These analyses are known to cause matrix effects. METHODS: The presented study describes the elimination of matrix effects for ethyl glucuronide. This study used two different LC/MS/MS systems containing orthogonal and z-spray ion sources. Ethyl glucuronide was analyzed in negative polarity in electrospray ionization. A different dilution method was chosen for each study. The methods were developed and validated according to the European Medicines Agency bioanalytical method validation parameters. RESULTS: The lower limit of quantitation of the developed methods was 0.025 µg/mL for ethyl glucuronide. The calibration curve of ethyl glucuronide was between 0.025 and 100 µg/mL with a correlation coefficient of >0.99 for the two methods. CONCLUSIONS: It was determined that the analyses using the z-spray ion source were more affected by the matrix effect. The two validated methods involve rapid analysis time and simple sample preparation. Also, the methods were applied to real patients' urine.

Evaluation of Alcohol Markers in Urine and Oral Fluid after Regular and Hard Kombucha Consumption.

Although kombucha is a popular fermented beverage, the presence of alcohol markers has not been well studied despite being potential indicators of unintentional impairment. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) were measured in oral fluid and urine collected after consumption of regular or hard kombucha. Participants drank within 20 min and provided all urine voids for 12 h, the first urine voids on days 2 and 3 and oral fluid specimens at fixed time points for 48 h. Screening employed liquid chromatography-tandem mass spectrometry (LC-MS-MS; EtS, 25 ng/mL cutoff [oral]; 100 ng/mL cutoff [urine]; EtG, 500 ng/mL cutoff [urine] and immunoassay (IA; EtG, 500 ng/mL cutoff [urine]). After consuming regular kombucha (n = 12 participants), EtS was not detected in oral fluid but both markers were detected by LC-MS-MS in urine specimens within the first five voids from 83% of participants with median (range) concentrations of 240 (100-3,700) ng/mL for EtS and 830 (530-2,200) ng/mL for EtG. Neither marker was positive by IA nor LC-MS-MS after day 1. After consuming hard kombucha (n = 7 participants), 2 (2.8%) of the 70 collected oral fluid specimens tested positive for EtS 3 h after consumption; however, 21 (30%) had EtS levels above the limit of detection (LOD, 10 ng/mL) after 0.5-8 h. Both markers were detected in urine specimens from all participants with median (range) concentrations of 3,381 (559-70,250) ng/mL for EtS and 763 (104-12,864) ng/mL For EtG. Urine specimens were negative for EtG and EtS by the end of the 48-hour study.

Concordance Between Point-of-Care Urine Ethyl Glucuronide Alcohol Tests and Self-Reported Alcohol Use in Persons with HIV in Uganda.

Screening and assessing alcohol use accurately to maximize positive treatment outcomes remain problematic in regions with high rates of alcohol use and HIV and TB infections. In this study, we examined the concordance between self-reported measures of alcohol use and point-of-care (POC) urine ethyl glucuronide (uEtG) test results among persons with HIV (PWH) in Uganda who reported drinking in the prior 3 months. For analyses, we used the screening data of a trial designed to examine the use of incentives to reduce alcohol consumption and increase medication adherence to examine the concordance between POC uEtG (300 ng/mL cutoff) and six measures of self-reported alcohol use. Of the 2136 participants who completed the alcohol screening, 1080 (50.6%) tested positive in the POC uEtG test, and 1756 (82.2%) self-reported using alcohol during the prior 72 h. Seventy-two percent of those who reported drinking during the prior 24 h had a uEtG positive test, with lower proportions testing uEtG positive when drinking occurred 24-48 h (64.7%) or 48-72 h (28.6%) prior to sample collection. In multivariate models, recency of drinking, number of drinks at last alcohol use, and Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) score were associated with uEtG positivity. The highest area under the curve (AUC) for a uEtG positive test was for recency of drinking. Overall, we concluded that several measures of drinking were associated with POC uEtG positivity, with recency of drinking, particularly drinking within the past 24 h, being the strongest predictor of uEtG positivity.

Alcohol Consumption Moderated the Association Between Levels of High Blood Lead or Total Urinary Arsenic and Bone Loss.

Metal exposure and lifestyle are important risk factors for osteoporosis. Our study aimed to investigate the association between red blood cell lead and cadmium, total urinary arsenic, and plasma selenium levels and bone mineral density (BMD). In addition, we explored whether alcohol and coffee consumption modified the association between BMD and metals and metalloids. In total, 437 participants who underwent adult or senile physical examinations were recruited. Bone loss was defined as a calcaneus BMD T-score of <-1. Blood cadmium and lead and plasma selenium levels were measured using inductively coupled plasma mass spectrometry. Levels of urinary arsenic species were determined using high-performance liquid chromatography-hydride generator-atomic absorption spectrometry. The total urinary arsenic level was defined as the sum of the levels of urinary arsenic species. The BMD T-scores decreased significantly with increasing blood lead levels. The BMD T-scores also showed a downward trend with increasing total urinary arsenic levels. The odds ratio (OR) and 95% confidence interval (CI) for bone loss in patients with blood lead levels >57.58 versus 35.74 µg/dL were 1.98 and 1.17-3.34. In addition, the greater the lead or arsenic exposure and alcohol intake was the higher the OR for bone loss with multivariate ORs of 2.57 (95% CI 1.45-4.56) and 2.96 (95% CI 1.67-5.22), respectively. To the best of our knowledge, this study is the first to demonstrate that high total urinary arsenic or blood lead levels and frequent or occasional alcohol consumption had a significant multiplicative interaction for increasing the OR for bone loss.

Urinary Tartaric Acid, a Biomarker of Wine Intake, Correlates with Lower Total and LDL Cholesterol.

Postmenopausal women are at higher risk of developing cardiovascular diseases due to changes in lipid profile and body fat, among others. The aim of this study was to evaluate the association of urinary tartaric acid, a biomarker of wine consumption, with anthropometric (weight, waist circumference, body mass index (BMI), and waist-to-height ratio), blood pressure, and biochemical variables (blood glucose and lipid profile) that may be affected during the menopausal transition. This sub-study of the PREDIMED (Prevención con Dieta Mediterránea) trial included a sample of 230 women aged 60-80 years with high cardiovascular risk at baseline. Urine samples were diluted and filtered, and tartaric acid was analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Correlations between tartaric acid and the study variables were adjusted for age, education level, smoking status, physical activity, BMI, cholesterol-lowering, antihypertensive, and insulin treatment, total energy intake, and consumption of fruits, vegetables, and raisins. A strong association was observed between wine consumption and urinary tartaric acid (0.01 µg/mg (95% confidence interval (CI): 0.01, 0.01), p-value < 0.001). Total and low-density lipoprotein (LDL) cholesterol were inversely correlated with urinary tartaric acid (-3.13 µg/mg (-5.54, -0.71), p-value = 0.016 and -3.03 µg/mg (-5.62, -0.42), p-value = 0.027, respectively), whereas other biochemical and anthropometric variables were unrelated. The results suggest that wine consumption may have a positive effect on cardiovascular health in postmenopausal women, underpinning its nutraceutical properties.

Clinical usefulness of a urine dipstick to detect ethyl glucuronide (EtG): A quantitative clinical study in healthy young female volunteers.

The metabolite of ethanol, ethyl glucuronide (EtG), reflects alcohol intake longer than ethanol and is used as a biomarker in clinical settings to detect alcohol use. We aimed to assess the clinical usefulness in a low-to-moderate alcohol intake setting and validate a new urine EtG dipstick. A three-way, open, cross-over trial was conducted. Data were collected from January to June 2019. Among 12 healthy female volunteers, we quantified urine EtG and used a dipstick following intake of either one, two or four units of alcohol. Main outcomes were concentrations of EtG in urine and serum, and creatinine and ethanol in serum. EtG in urine was determined dichotomously by dipsticks at two different thresholds and by mass spectrometry used as gold standard. EtG in urine was quantifiable up to 24 hours after alcohol intake. In some individual cases, EtG was quantifiable up to 72 hours at low concentrations. The dipstick detected EtG in urine up to 24 hours. At thresholds of 1000 and 1500 ng/mL, the dipsticks had a specificity of 100% (both), while sensitivity was 84% and 69%, respectively. The sensitivity of the dipsticks was insufficient to support a screening purpose in this setting of low-to-moderate alcohol intake.

Changes in alcohol consumption associated with social distancing and self-isolation policies triggered by COVID-19 in South Australia: a wastewater analysis study.

AIM: To assess the effects of social distancing and social isolation policies triggered by COVID-19 on alcohol consumption using wastewater analysis in Adelaide, South Australia. DESIGN: Longitudinal quantitative analysis of influent wastewater data for alcohol concentration. SETTING: Adelaide, South Australia. PARTICIPANTS: Wastewater catchment area representative of 1.1 million inhabitants. MEASUREMENTS: Twenty-four hour composite influent wastewater samples were collected from four wastewater treatment plants in Adelaide, South Australia for 7 consecutive days (Wednesday-Tuesday) every 2 months from April 2016-April 2020. The alcohol metabolite ethyl sulfate was measured in samples using chromatography-tandem mass spectrometry. Data were population-weighted adjusted with consumption expressed as standard drinks/day/1000 people. Weekly consumption and weekend to mid-week consumption ratios were analysed to identify changes in weekday alcohol use pattern. FINDINGS: Estimated weekend alcohol consumption was significantly lower (698 standard drinks/day/1000 people) after self-isolation measures were enforced in April 2020 compared with the preceding sampling period in February 2020 (1047 standard drinks/day/1000 people), P < 0.05. Weekend to midweek consumption ratio was 12% lower than the average ratio compared with all previous sampling periods. April 2020 recorded the lowest alcohol consumption relative to April in previous years, dating back to 2016. CONCLUSIONS: Wastewater analysis suggests that introduction of social distancing and isolation policies triggered by COVID-19 in Adelaide, South Australia, was associated with a decrease in population-level weekend alcohol consumption.

Alcohol substitution during one month of cannabis abstinence among non-treatment seeking youth.

OBJECTIVE: Cannabis and alcohol use are correlated behaviors among youth. It is not known whether discontinuation of cannabis use is associated with changes in alcohol use. This study assessed alcohol use in youth before, during, and after 4 weeks of paid cannabis abstinence. METHODS: Healthy, non-treatment seeking, cannabis users (n = 160), aged 14-25 years, 84% of whom used alcohol in the last month, were enrolled for a 4-week study with a 2-4 week follow-up. Participants were randomly assigned to 4 weeks of either biochemically-verified cannabis abstinence achieved through a contingency management framework (CB-Abst) or monitoring with no abstinence requirement (CB-Mon). Participants were assessed at baseline and approximately 4, 6, 10, 17, 24, and 31 days after enrollment. A follow-up visit with no cannabis abstinence requirement for CB-Abst was conducted after 2-4 weeks. RESULTS: Sixty percent of individuals assigned to the CB-Abst condition increased in frequency and quantity of alcohol consumption during the 4-week period of incentivized cannabis abstinence. As a whole, CB-Abst increased by a mean of 0.6 drinking days and 0.2 drinks per day in the initial week of abstinence (p's < 0.006). There was no evidence for further increases in drinking frequency or quantity during the 30-day abstinence period (p's > 0.53). There was no change in drinking frequency or quantity during the 4-week monitoring or follow-up periods among CB-Mon. CONCLUSIONS: On average, 4 weeks of incentivized (i.e., paid) cannabis abstinence among non-treatment seeking youth was associated with increased frequency and amount of alcohol use in week 1 that was sustained over 4 weeks and resolved with resumption of cannabis use. However, there was notable variability in individual-level response, with 60% increasing in alcohol use and 23% actually decreasing in alcohol use during cannabis abstinence. Findings suggest that increased alcohol use during cannabis abstinence among youth merits further study to determine whether this behavior occurs among treatment seeking youth and its clinical significance.

Ethyl Glucuronide and Ethyl Sulphate in Urine: Caution in their use as markers of recent alcohol use.

AIM: To clarify the role of the ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), in monitoring alcohol consumption. METHOD: We recruited 7 female and 17 male volunteers who were instructed to consume a quantity of beer (containing 48 gm ethanol) with food in one session. We examined urinary excretion of EtG and EtS over time and looked for correlations between the concentrations of the metabolites EtG and EtS. RESULTS: EtG concentrations in urine varied between 0.026 and 430.372 µg/ml with average values between 11.85 µg/ml (SD 19.75), 30 min after alcohol intake, and 100.39 µg/ml (SD 101.34), 4.5 h after alcohol intake. EtS urinary concentration ranged from 0.006 to 101.432 µg/ml with average values between 4.77 µg/ml (SD 5.42), 30 min after alcohol intake, and 30.14 µg/ml (SD 27.20), 4.5 h after alcohol intake. Spearman's test showed that urinary EtG and EtS correlated significantly at several time points. CONCLUSION: The great interindividual variability in their excretion suggests caution in the use of urinary measurement of these metabolites in forensic investigations.

As3MT and GST Polymorphisms Influencing Arsenic Metabolism in Human Exposure to Drinking Groundwater.

The urinary arsenic metabolites may vary among individuals and the genetic factors have been reported to explain part of the variation. We assessed the influence of polymorphic variants of Arsenic-3-methyl-transferase and Glutathione-S-transferase on urinary arsenic metabolites. Twenty-two groundwater wells for human consumption from municipalities of Colombia were analyzed for assessed the exposure by lifetime average daily dose (LADD) (µg/kg bw/day). Surveys on 151 participants aged between 18 and 81 years old were applied to collect demographic information and other factors. In addition, genetic polymorphisms (GSTO2-rs156697, GSTP1-rs1695, As3MT-rs3740400, GSTT1 and GSTM1) were evaluated by real time and/or conventional PCR. Arsenic metabolites: AsIII, AsV, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured using HPLC-HG-AFS. The influence of polymorphic variants, LADD and other factors were tested using multivariate analyses. The median of total arsenic concentration in groundwater was of 33.3 µg/L and the median of LADD for the high exposure dose was 0.33 µg/kg bw/day. Univariate analyses among arsenic metabolites and genetic polymorphisms showed MMA concentrations higher in heterozygous and/or homozygous genotypes of As3MT compared to the wild-type genotype. Besides, DMA concentrations were lower in heterozygous and/or homozygous genotypes of GSTP1 compared to the wild-type genotype. Both DMA and MMA concentrations were higher in GSTM1-null genotypes compared to the active genotype. Multivariate analyses showed statistically significant association among interactions gene-gene and gene-covariates to modify the MMA and DMA excretion. Interactions between polymorphic variants As3MT*GSTM1 and GSTO2*GSTP1 could be potential modifiers of urinary excretion of arsenic and covariates as age, LADD, and alcohol consumption contribute to largely vary the arsenic individual metabolic capacity in exposed people.

Utility of Ethyl-Glucuronide for Evaluation of Abstinence in Patients Presenting for Liver Transplantation.

BACKGROUND: Cirrhosis as a result of alcohol-related liver disease is one of the most common indications for liver transplantation (LT) in Spain. Patients presenting for LT should be checked for alcohol abuse in clinical interviews and use of laboratory tests to confirm abstinence. The ethyl-glucuronide (EtG) test is very sensitive and can be positive in urine up to 5 days after consumption. Our main objective is to know the rate of alcohol abstinence by using the urine EtG test in patients evaluated for LT and to assess its correlation with the clinical interviews and laboratory test. METHODS: We conducted a prospective analysis of the results of the EtG in urine of patients evaluated for LT from January 2017 to March 2019 and its correlation with the medical and psychiatric interviews and with the laboratory test. RESULTS: We included 160 patients who were referred to LT evaluation. Among all cases, 84.1% were men, with an average age of 57.8 years. Alcohol-related liver disease was the most frequent cause (64.1%). Urine-EtG was positive in 10 patients (6.2%), 9 of them in patients with ALD and 1 in a patient with hepatitis C virus. The alcohol consumption was recognized by 80% of the patients in the clinical interview. Cases with positive EtG had higher levels of analytical parameters than those with a negative test. CONCLUSIONS: In our series, 6.2% of patients referred for LT evaluation had recently consumed alcohol. The determination of EtG in urine is probably an effective and objective technique in the detection of alcohol consumption to ensure abstinence in the LT candidates.

The roles of phosphatidylethanol, ethyl glucuronide, and ethyl sulfate in identifying alcohol consumption among participants in professionals health programs.

Direct alcohol biomarkers, including urinary ethyl glucuronide (EtG), urinary ethyl sulfate (EtS), and blood phosphatidylethanol (PEth), are used to monitor alcohol abstinence in individuals who are mandated to abstain. In this consecutive case series study, we examined 1000 forensic reports of participants enrolled in a professionals health program who were contractually obligated to abstain from alcohol and who underwent recovery status evaluations. We identified 52 evaluations in which urinary EtG, EtS, and blood PEth were measured and which produced a positive result for at least one of these analytes. PEth, at a cutoff concentration of 20 ng/mL, revealed alcohol use more frequently than EtG or EtS at our laboratory's cutoff concentrations of 100 and 25 ng/mL, respectively. This was true, as well, at alternative EtG/EtS cutoff concentrations of 200/50, 300/75, and 400/100 ng/mL. PEth was more likely than EtG/EtS to be positive in participants previously diagnosed with alcohol use disorders (AUD), whereas EtG/EtS was more likely than PEth to be positive in participants without AUD. In this study, blood PEth was the most sensitive biomarker for evidencing alcohol use.

Urinary Ethyl Glucuronide as Measure of Alcohol Consumption and Risk of Cardiovascular Disease: A Population-Based Cohort Study.

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.

Distributions of alcohol use biomarkers including ethanol, phosphatidylethanol, ethyl glucuronide and ethyl sulfate in clinical and forensic testing.

Laboratory tests vary widely in their utility and each test has unique advantages and disadvantages. For the detection of ethanol use and abuse, a variety of direct and indirect markers are available. Alcohol biomarkers provide objective measures for numerous areas of testing including clinical trials, alcohol abuse, postmortem assessment, and drugs of abuse screening. Because the utility of alcohol biomarkers vary depending on the context in which the results will be used, knowing the analogous distribution of results is of value. Herein we report distributions of ethanol in blood, phosphatidylethanol in blood, ethyl glucuronide in urine, and ethyl sulfate in urine for results reported in the last twelve months by our laboratory. Positivity rates were higher for directed analyses when compared to broad screening or panel tests with the highest overall positivity for ethyl glucuronide and ethyl sulfate. The distribution of results for ethyl glucuronide and ethyl sulfate were higher in clinical testing scenarios compared to forensic and a significant correlation between ethyl glucuronide and ethyl sulfate was found consistent with previous reports. Phosphatidylethanol was rarely ordered for forensic use while distributions between routine clinical and clinical trial use were similar. Approximately 21% of all phosphatidylethanol results were in the moderate to chronic alcohol use category. These results provide a summary of four commonly used direct markers for alcohol use with positivity rates and overall quantitative distributions. These data supply insights broken out by various disciplines where applicable providing a concise comparison of results for these markers.

Persistent Urinary Ethyl Sulfate in the Absence of Urinary Ethyl Glucuronide in a Patient with Alcohol Use Disorder Who Claimed Abstinence.

A 48-year-old nurse with an alcohol use disorder history was being monitored in a professional health program. She consistently produced low-to-moderate urinary ethyl sulfate (EtS) concentrations in the absence of detectable urinary ethyl glucuronide (EtG), blood phosphatidylethanol and breath alcohol. She denied intentional ethanol consumption. After prolonged monitoring in a drug treatment program, including a period in a controlled environment, we concluded that this individual's urinary EtS likely resulted from anatomical and microbial factors related to Roux-en-Y gastric bypass surgery, with possible contributions from hidden dietary sources of ethanol. We have no definitive explanation for the lack of urinary EtG.

Alterations in circadian rhythms following alcohol use: A systematic review.

Increasing evidence suggest a bidirectional link between disrupted circadian rhythms and alcohol use disorders (AUD). A better understanding of these alcohol-induced changes in circadian rhythms will likely provide important therapeutic solutions. We conducted a systematic review based on the PubMed database examining biological rhythms in all stages of alcohol use: acute alcohol consumption, AUD, alcohol withdrawal, and abstinence. Different changes in circadian rhythms have been observed after a single acute alcohol intake, but also during AUD and alcohol withdrawal. Following a single acute alcohol intake, changes in biological rhythms are dose-dependent, reflected in the melatonin and cortisol secretions, and the core body temperature (CBT) rhythms. These alterations normalize the next morning and appear mostly for acute alcohol intake higher than 0.5 g/kg. These alterations are more severe during AUD and persist over time. In addition, interestingly, opposite patterns of the melatonin physiological ratio between diurnal and nocturnal secretion (N/D ratio < 1) have been observed during AUD and appear to be a marker of chronic daily use. During alcohol withdrawal, circadian rhythms desynchronization correlates with the severity of alcohol withdrawal symptoms and withdrawal complications such as delirium tremens. During abstinence a resynchronization of circadian rhythms of cortisol and CBT appears in most patients about 1 month after alcohol withdrawal. Disruption of melatonin circadian rhythms can persist after 3-12 weeks of abstinence. The circadian genetic vulnerability associated with biological rhythms alterations in alcohol use disorders increases the risk of relapses. Circadian-based interventions could play a critical role in preventing and treating AUD.

Evaluating the hip-flask defence in subjects with alcohol on board: An experimental study.

Driving under the influence of alcohol is a major problem for traffic-safety and a popular defence argument is alleged consumption after driving, commonly referred to as the hip-flask defence. Forensic toxicologists are often called as expert witnesses in drinking and driving cases where the suspect has claimed the hip-flask defence, to assess the credibility of the explanation. Several approaches to help the expert have been introduced but the scientific data used to support or challenge this is solely based on data from controlled single doses of ethanol administered during a short time and in abstinent subjects. In reality, we believe that even in drinking after driving cases, the subject many times has alcohol on board at time of the hip-flask drink. This questions the applicability of the data used as basis to investigate the hip-flask defence. To fill this knowledge gap, we aimed to investigate how blood and urine ethanol kinetics vary after an initial drinking session of beer and then a subsequent hip-flask drink of three different doses of whiskey. Fifteen subjects participated in the study and each provided 10 urine samples and 17 blood samples over 7h. The initial drink was 0.51g ethanol/kg and the second was either 0.25, 0.51, or 0.85g/kg. Our data suggested that the difference between the ethanol concentrations in two consecutive urine samples is a more sensitive parameter than the ratio between urine and blood alcohol to detect a recent intake when ethanol from previous intakes are already present in the body. Twelve subjects presented results that fully supported a recent intake using the criteria developed from a single intake of ethanol. Three subjects showed unexpected results that did not fully support a recent intake. We conclude that data from one blood sample and two urine samples provide good evidence for investigating the hip-flask defence even if alcohol was on board at the time of the hip-flask drink.

Alcohol Biomarkers in Clinical and Forensic Contexts.

BACKGROUND: Biomarkers of alcohol consumption are important not only in forensic contexts, e.g., in child custody proceedings or as documentation of alcohol abstinence after temporary confiscation of a driver's license. They are increasingly being used in clinical medicine as well for verification of abstinence or to rule out the harmful use of alcohol. METHODS: This review is based on pertinent publications that were retrieved by a selective literature search in PubMed concerning the direct and indirect alcohol markers discussed here, as well as on the authors' experience in laboratory analysis and clinical medicine. RESULTS: Alongside the direct demonstration of ethanol, the available markers of alcohol consumption include the classic indirect markers carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and mean corpuscular volume (MCV) as well as direct alcohol markers such as ethyl glucuronide (EtG) and ethyl sulfate (EtS) in serum and urine and EtG and fatty acid ethyl esters (FAEE) in hair. Phosphatidylethanol (PEth) is a promising parameter that com - plements the existing spectrum of tests with high specificity (48-89%) and sensi - tivity (88-100%). In routine clinical practice, the demonstration of positive alcohol markers often leads patients to admit previously denied alcohol use. This makes it possible to motivate the patient to undergo treatment for alcoholism. CONCLUSION: The available alcohol biomarkers vary in sensitivity and specificity with respect to the time period over which they indicate alcohol use and the minimum extent of alcohol use that they can detect. The appropriate marker or combination of markers should be chosen in each case according to the particular question that is to be answered by laboratory analysis.

GC-MS-based urinary organic acid profiling reveals multiple dysregulated metabolic pathways following experimental acute alcohol consumption.

Metabolomics studies of diseases associated with chronic alcohol consumption provide compelling evidence of several perturbed metabolic pathways. Moreover, the holistic approach of such studies gives insights into the pathophysiological risk factors associated with chronic alcohol-induced disability, morbidity and mortality. Here, we report on a GC-MS-based organic acid profiling study on acute alcohol consumption. Our investigation - involving 12 healthy, moderate-drinking young men - simulated a single binge drinking event, and indicated its metabolic consequences. We generated time-dependent data that predicted the metabolic pathophysiology of the alcohol intervention. Multivariate statistical modelling was applied to the longitudinal data of 120 biologically relevant organic acids, of which 13 provided statistical evidence of the alcohol effect. The known alcohol-induced increased NADH:NAD+ ratio in the cytosol of hepatocytes contributed to the global dysregulation of several metabolic reactions of glycolysis, ketogenesis, the Krebs cycle and gluconeogenesis. The significant presence of 2-hydroxyisobutyric acid supports the emerging paradigm that this compound is an important endogenous metabolite. Its metabolic origin remains elusive, but recent evidence indicated 2-hydroxyisobutyrylation as a novel regulatory modifier of histones. Metabolomics has thus opened an avenue for further research on the reprogramming of metabolic pathways and epigenetic networks in relation to the severe effects of alcohol consumption.

Text Messaging to Reduce Alcohol Relapse in Prelisting Liver Transplant Candidates: A Pilot Feasibility Study.

BACKGROUND: Many liver transplantation programs require documented alcohol sobriety prior to United Network for Organ Sharing (UNOS) listing. This pilot study examined the feasibility of the first mobile, alcohol relapse prevention intervention for liver transplant patients with alcoholic liver disease (ALD). METHODS: This was a randomized 8-week pilot feasibility trial of a text message-based alcohol intervention. In-treatment assessment was conducted at 4 weeks (4W), and immediate posttreatment assessment was conducted at 8W. Participants were liver transplant candidates (N = 15) diagnosed with ALD who reported at least 1 drinking episode in the past year. Primary feasibility outcomes were percent of messages responded to and posttreatment intervention satisfaction ratings. Preliminary clinical efficacy outcomes were any biologically confirmed alcohol consumption, stress, abstinence self-efficacy, and alcohol craving. RESULTS: On feasibility outcomes, participants responded to 81% of messages received and reported high rates of intervention satisfaction, looked forward to receiving the messages, and found it easy to complete the intervention. On preliminary efficacy outcomes, zero participants in the text message (TM) had positive urine alcohol tests at 8W. Two of the 6 participants in standard care (SC) tested positive at 8W. No effects were seen on craving. For stress, a condition × time interaction emerged. TM participants had less stress at 4W and 8W compared with SC at baseline. They maintained their stress level during the intervention. For self-efficacy, a trend for condition effect emerged. TM participants had higher self-efficacy than SC participants. CONCLUSIONS: Participants reported high satisfaction with the intervention, looked forward to the messages, and found it easy to complete. Participants who received the intervention had better treatment outcomes than those who received standard care. They maintained higher levels of self-efficacy and lower stress. Mobile alcohol interventions may hold significant promise to help ALD liver transplant patients maintain sobriety.