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Background: Alcohol use after liver transplant (LT) is associated with higher rates of graft loss and increased mortality; however, there are limited data evaluating predictors of return to alcohol use using biochemical markers like phosphatidylethanol (PEth). Methods: This multicenter retrospective cohort study evaluated psychosocial predictors of return to alcohol use using PEth testing in patients transplanted for alcohol‐associated liver disease (ALD). The study included 223 patients at three centers who had received a LT for ALD and had at least one PEth measurement post‐LT. Results: The rate of return to alcohol use was 6.9 cases per 100 person‐years (26 patients total) over a median 555 days of follow‐up after transplant. Younger age (HR 0.96; 95% CI 0.92–0.99, p = 0.02), mental health comorbidities (HR 2.83; 95% CI 1.25–6.39, p = 0.01), and non‐Hispanic White race (HR 3.79; 95% CI 1.42–10.15, p = 0.01) were associated with return to alcohol use post‐LT. There was no difference between post‐LT return to alcohol use rates or short‐term survival among patients with less than 6 months of sobriety prior to listing compared with those with more than 6 months. Patients with sustained alcohol use post‐LT had increased odds of history of illicit substance use (OR 5.20; 95% CI 1.01–26.83, p = 0.04) but no significant difference in time from the last drink to listing (OR 1.03; 95% CI 0.18–5.80, p = 0.97). Conclusions: These findings emphasize the importance of mental health comorbidities rather than period of sobriety in predicting post‐LT return to alcohol use. Furthermore, the higher risk of return to alcohol use in non‐Hispanic White patients suggests a potential disparity with referral and selection of higher risk White patients. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion and Conclusions Phosphatidylethanol (PEth) is a specific and persisting marker of ethanol (alcohol) consumption. Early success of medically necessary abstinence can be assessed by monitoring PEth disappearance at a biologically plausible rate. This requires an understanding of PEth elimination, its variability and its determinants. To achieve this, we characterised PEth elimination in drinkers who voluntarily abstained. We aimed to derive a nomogram from the data to assist practitioners in recognising abstinence.Twenty‐nine usual drinkers who were prepared to abstain from alcohol consumption for 4 weeks were recruited. Erythrocyte PEth was measured weekly. A population pharmacokinetic model for PEth was developed, describing the time‐course of PEth elimination. Estimates were derived for population average, inter‐individual variability in PEth half‐life and any covariate influences. These estimates informed a nomogram of PEth elimination that incorporated a boundary separating continued abstinence from resumed drinking. The nomogram was tested to identify drinking events among participants.The model estimated a population average elimination rate constant (k) of 0.088 day−1, corresponding to a half‐life of 7.9 days with a residual coefficient of variation of 8.5%. Elimination was first order and no covariate influences were identified. The nomogram was internally assessed as predictively accurate for 21 successfully abstinent participants and in detecting alcohol consumption in 2 further participants, using a 99.9% prediction interval.The value of PEth in distinguishing alcohol abstinence from consumption is enhanced by using a nomogram to confirm abstinence within weeks of its medically necessary imposition. Further work will establish the value of this approach in clinical practice. [ABSTRACT FROM AUTHOR]

Phosphatidylethanol (PEth) is an alcohol derivative that has been employed as a blood-based biomarker for regular alcohol use. This study investigates the utility of phosphatidylethanol (PEth) as a biomarker for assessing alcohol consumption in post-mortem brain tissue. Using samples from the New South Wales Brain Tissue Resource Centre, we analysed PEth(16:0/18:1) levels in the cerebellum and meninges of individuals with varying histories of alcohol use, including those diagnosed with alcohol use disorder (AUD) and controls. Our findings demonstrate a significant correlation between PEth levels and blood alcohol content (BAC) at the time of death, supporting the biomarker's sensitivity to recent alcohol intake. Furthermore, this study explores the potential of PEth levels in differentiating AUD cases from controls, taking into consideration the complexities of diagnosing AUD post-mortem. The study also examined the relationship between PEth levels and liver pathology, identifying a link with the severity of liver damage. These results underscore the value of PEth as a reliable indicator of alcohol consumption and its potential contributions to post-mortem diagnostics and consequently, research into alcohol-related brain damage. • Phosphatidylethanol is a derivative of alcohol metabolism. • The assay is used to indicate recent alcohol drinking and largely from blood. • We show that phosphatidylethanol can be similarly assayed in post-mortem brain tissue. • This allows more accurate and informative research on alcohol-related brain damage. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the alcohol consumption among professional truck and bus drivers using direct ethanol biomarkers, and to explore its relationship with anxiety, depression, and stress. The assessment of potential harmful drinking was conducted through the measurement of direct biomarkers: phosphatidylethanol (PEth), ethyl glucuronide (EtG), and ethyl sulfate (EtS), using dried blood spots (DBS). Additionally, self-reported data from the Alcohol Use Disorders Identification Test (AUDIT-C) were used. Emotional states, including depression, anxiety, and stress, were evaluated using the Depression, Anxiety, and Stress Scale (DASS-21). A total of 97 drivers participated in the study, with the majority being male (96%) and identified as truck drivers (75.3%). Among them, 43.3% reported working more than 10 h daily. The majority of volunteers exhibited normal levels of stress (81.4%), anxiety (83%), and depression (86.6%). According to the AUDIT-C assessment, 30.9% were categorized as having a moderate risk, while 11.3% were deemed to be at high risk for harmful alcohol consumption behavior. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) levels, indicating recent ethanol consumption, were detected in 14.4% of the drivers. In contrast, the long half-life metabolite PEth (16:0-18:1) was present in 88.7% of the volunteers. A moderate correlation (rs = 0.45, p <.01) was observed between PEth levels and AUDIT-C scores. The Receiver Operating Characteristic (ROC) curve, utilizing a PEth threshold of ≥ 59.0 ng ml−1, displayed 78% sensitivity and 73% specificity in effectively distinguishing high risk for alcohol intake. Notably, no significant associations were found between alcohol consumption and levels of stress, depression, and anxiety. The study findings indicate a noteworthy proportion of drivers engaging in regular alcohol consumption alongside a demanding workload. Notably, PEth measurements highlighted an underreporting within the AUDIT-C self-reports. These results lend robust support for the utilization of biomarkers in assessing alcohol consumption patterns among drivers. [ABSTRACT FROM AUTHOR]

Aims To investigate the association between alcohol consumption registered daily with a digital smartphone-based diary and concentration of phosphatidylethanol (PEth) 16:0/18:1 in a population without a known alcohol use disorder (AUD), and evaluate whether prospective registration of alcohol consumption is better than retrospective registration and if the association between alcohol intake and PEth was affected by sex or body mass index (BMI). Methods A total of 41 women and 21 men without AUD-diagnosis registered their alcohol consumption prospectively with a digital diary for 14 days, and retrospectively with the Timeline Followback method in the same time interval. PEth was measured before and after the registration period. Results The correlation between alcohol consumption and PEth varied from 0.65 to 0.87. It did not depend significantly on the reporting method, and was not influenced by sex or BMI. Based on the regression coefficient, a reduction of alcohol consumption by two alcohol units (26 g of pure ethanol) per day would lead to a reduction of the PEth concentration of about 0.1 μmol/l, and vice versa. Conclusions There was a good correlation between PEth concentration and alcohol consumption, both when alcohol consumption was reported prospectively and retrospectively. The preferred cut-off for PEth should be adjusted to the level of alcohol consumption considered harmful and a purposeful trade-off between sensitivity and specificity. In order to identify persons with a daily alcohol consumption of more than two or three units of alcohol with a sensitivity of 80% or 90%, we suggest a cut-off of around 0.1 μmol/l. [ABSTRACT FROM AUTHOR]

Serum phosphatidylethanol (PEth) testing has emerged as a promising biomarker for assessing recent alcohol consumption, surpassing the limitations of self-reported data. Limited clinical data exists comparing PEth levels and patients' reported alcohol intake. Compare PEth testing results with self-reported alcohol intake and assesses variables associated with underreporting. Single-center retrospective cohort of patients with a diagnosis of chronic liver disease and serum PEth. A patient's first positive PEth (>/=10 ng/mL) and self-reported alcohol consumption was used. PEth results were categorized as mild (10–20), moderate (20–200), or heavy (>200). Severity measures between self-report and PEth were assessed using Bhapkar's test and Bonferroni-adjusted McNemar's tests. Demographic data was analyzed using Chi-Square tests. 279 patients were included. 94 (33.7%) patients had consistency with self-report, and 185 patients had inconsistencies in their report (66.3%, p < 0.001). Of 279 patients, 161 (57.7%) underreported their alcohol consumption, and 55 (19.7%) heavy PEth patients underreported alcohol consumption as light. 58% of alcohol-related and 56.4% of non-alcohol-related cirrhotic patients underreported their alcohol use. In our cohort, only one third of self-reported alcohol consumption was consistent with the PEth level. Notably, 57.7% underreported alcohol intake. Our study reinforces the clinical importance of PEth testing as an objective clinical measure. [ABSTRACT FROM AUTHOR]

This article traces the historical development of various biomarkers of acute and/or chronic alcohol consumption. Much of the research in this domain of clinical and laboratory medicine arose from clinics and laboratories in Sweden, as exemplified by carbohydrate deficient transferrin (CDT) and phosphatidylethanol (PEth). Extensive studies of other alcohol biomarkers, such as ethyl glucuronide (EtG), ethyl sulfate (EtS), and 5‐hydroxytryptophol (5‐HTOL), also derive from Sweden. The most obvious test of recent drinking is identification of ethanol in a sample of the person's blood, breath, or urine. However, because of continuous metabolism in the liver, ethanol is eliminated from the blood at a rate of 0.15 g/L/h (range 0.1–0.3 g/L/h), so obtaining positive results is not always possible. The widow of detection is increased by analysis of ethanol's non‐oxidative metabolites (EtG and EtS), which are more slowly eliminated from the bloodstream. Likewise, an elevated ratio of serotonin metabolites in urine (5‐HTOL/5‐HIAA) can help to disclose recent drinking after ethanol is no longer measurable in body fluids. A highly specific biomarker of hazardous drinking is CDT, a serum glycoprotein (transferrin), with a deficiency in its N‐linked glycosylation. Another widely acclaimed biomarker is PEth, an abnormal phospholipid synthesized in cell membranes when people drink excessively, having a long elimination half‐life (median ~6 days) during abstinence. Research on the subject of alcohol biomarkers has increased appreciably and is now an important area of drug testing and analysis. [ABSTRACT FROM AUTHOR]

Alcohol use is especially problematic for people living with HIV (PLWH) and was likely to be impacted by the coronavirus disease (COVID-19) pandemic and its restrictions. In a study of PLWH with latent tuberculosis infection, we measured unhealthy alcohol use with the Alcohol Use Disorders Identification Test (AUDIT-C), phosphatidylethanol (PEth) and bar attendance. We analyzed data collected before and after COVID-19 restrictions, and used Generalized Estimating Equations (GEE) logistic regression models to evaluate changes in unhealthy alcohol use. While bar attendance declined from 57.0% before to 38.3% after the restrictions started, multivariable analysis controlling for bar use showed a significant increase in unhealthy alcohol use; the adjusted odds ratio for unhealthy drinking before versus after the restrictions started was 1.37 (95% CI: 0.89-2.12) which increased to 1.64 (95% CI: 1.08-2.50) when bar attendance was added to the model. Decline in bar attendance did not decrease unhealthy alcohol use.

BACKGROUND: Accurately quantifying alcohol use among persons with HIV (PWH) is important for validly assessing the efficacy of alcohol reduction interventions. METHODS: We used data from a randomized controlled trial of an intervention to reduce alcohol use among PWH who were receiving antiretroviral therapy in Tshwane, South Africa. We calculated agreement between self-reported hazardous alcohol use measured by the Alcohol Use Disorders Identification Test (AUDIT; score ≥8) and AUDIT-Consumption (AUDIT-C; score ≥3 for females and ≥4 for males), heavy episodic drinking (HED) in the past 30 days, and heavy drinking in the past 7 days with a gold standard biomarker--phosphatidylethanol (PEth) level (≥50 ng/mL)--among 309 participants. We used multiple logistic regression to assess whether underreporting of hazardous drinking (AUDIT-C vs. PEth) differed by sex, study arm, and assessment time point. RESULTS: Participants mean age was 40.6 years, 43% were males, and 48% were in the intervention arm. At 6 months, 51% had PEth ≥50 ng/mL, 38% and 76% had scores indicative of hazardous drinking on the AUDIT and AUDIT-C, respectively, 11% reported past 30-day HED, and 13% reported past 7-day heavy drinking. At 6 months, there was low agreement between AUDIT-C scores and past 7-day heavy drinking relative to PEth ≥50 (sensitivities of 83% and 20% and negative predictive values of 62% and 51%, respectively). Underreporting of hazardous drinking at 6 months was associated with sex (OR = 3.504. 95% CI: 1.080 to 11.364), with odds of underreporting being greater for females. CONCLUSIONS: Steps should be taken to decrease underreporting of alcohol use in clinical trials.

PURPOSE: To test the efficacy of two interventions to reduce alcohol use and increase viral suppression compared to a control in persons with HIV (PWH). METHODS: In a three-arm (1:1:1) randomized controlled trial (N = 269), we compared in-person counselling (45-70 minutes, two sessions over three months) with interim monthly booster phone calls (live call arm) or twice-weekly automated booster sessions (technology arm) to a brief advice control arm. We enrolled PWH self-reporting unhealthy alcohol use (Alcohol Use Disorders Identification Test - Consumption, prior three months, women ≥3, men ≥4). Primary outcomes were number of self-reported drinking days (NDD) in the prior 21 and biomarker phosphatidylethanol (PEth) at six and nine months and viral suppression (

Alcohol-associated liver disease has seen a significant rise in the last 2 decades, with an associated rise in the need for accurate alcohol use assessment. Alcohol use has been associated with poor outcomes in both the pre-liver transplant and post-liver transplant patients. Patients with alcohol use disorder often under-report their alcohol consumption because of varying factors, highlighting the need for objective assessment of alcohol use. Aside from the available self-report questionnaires, multiple serologic biomarkers are currently available to assist clinicians to assess recent alcohol consumption among patients with chronic liver disease, liver transplant candidates, and recipients. In this review, we will assess some of these alcohol biomarkers, discuss their strengths and weakness, and review-available data to discuss their role in pre-liver transplant and post-liver transplant population.

Phosphatidylethanol (PEth) is a direct alcohol biomarker to monitor individuals' drinking behavior that has gained recognition in clinical and forensic settings. The increasing application of the marker makes investigation of the preanalytical handling necessary, and analyte stability deserves major attention. This study was conducted to investigate the change of six PEth homologues' concentration, stored in authentic samples of EDTA blood over a course of 30 days at room temperature (n = 62). The stability criterion of concentration being ±15% of the original concentration was fulfilled at mean for 10, 3, 2, 5, 2, and 7 days for PEth 16:0/18:1, 16:0/18:2, 16:0/20:4, 18:0/18:1, 18:0/18:2, and 18:1/18:1, respectively. Regarding all homologues, there were samples in which concentration had declined by >15% or by more than the critical difference on day 1. Overall, calculated concentration declines were very inhomogeneous, with inter‐sample differences of 43%–73% after 30 days. PEth 16:0/18:2, 16:0/20:4, and 18:0/18:2 declined to a greater extent than PEth 16:0/18:1. Blood alcohol concentration was measured >0.1‰ in 25 samples. Three of the six samples that exceeded 115% of initial concentrations were positive for blood alcohol. The study results add to the previously reported information on PEth stability and firstly look at six homologues in comparison. Due to the high scatter of stability among the samples and the observed poor stabilities in some, it can be concluded that transportation and storage times, especially if cooling cannot be provided, must be kept short. If analyzing from dried blood, spotting should preferably be conducted at the site of sampling. [ABSTRACT FROM AUTHOR]

The aim of this study was to monitor seven phosphatidylethanol (PEth) homologues in dried blood spots (DBS) and ethyl glucuronide in hair (EtGH) over a 6‐month period of drinking while documenting the daily drinks (amount and type) of alcohol via app. A total of 23 volunteers (12 males and 11 females) aged 19–54 years were enrolled. At four‐weekly intervals, capillary blood to create DBS and after 3 and 6 months, respectively, a strand of hair (proximal, 3 cm) was collected. Analyses of EtGH and PEth homologues were performed using liquid chromatography–tandem mass spectrometry. All participants consumed alcohol during the 6 months. Only one participant tested negative for both PEth and EtGH. Eight participants had PEth 16:0/18:1 concentrations between 20 and <210 ng/mL (mean: 45.6 ng/mL) but EtGH concentrations below 5 pg/mg. PEth 16:0/18:1 concentrations between 20 and <210 ng/mL and EtGH concentrations between 5 and <30 pg/mg were assigned to eight subjects, uniformly matching them in the category of socially accepted drinking behavior. Four test subjects exceeded the cutoff for social drinking behavior in both PEth 16:0/18:1 (mean: 528 ng/mL) and EtGH (mean: 84.5 pg/mg). Two participants exceeded the threshold for PEth 16:0/18:1 of 210 ng/mL in blood but remained below 30 pg EtG/mg hair. PEth showed a higher detection rate for alcohol consumption than EtGH did. Moreover, PEth concentrations reacted quickly to changes in drinking behavior, whereas EtGH concentrations remained similar over time. [ABSTRACT FROM AUTHOR]

Phosphatidylethanol (PEth) is a non‐oxidative metabolite of alcohol (ethanol), which is a sensitive and specific indicator of historic ethanol consumption. Although PEth production from ethanol is catalysed by the ubiquitous enzyme phospholipase D, it resides mainly within the erythrocyte compartment of the blood. PEth analysis has been reported in different preparations of whole blood, representing one of the barriers of inter‐laboratory comparisons. We previously reported that expressing PEth concentrations in terms of blood erythrocyte content is more sensitive than whole blood volume, and haematocrit‐corrected liquid whole blood calculations of erythrocyte PEth and isolated erythrocyte PEth concentrations are comparable when assayed under identical analytical conditions. Acceptance of a clinical diagnostic assay by accreditation bodies requires proficiency testing with a third‐party analytical facility. To explore different blood preparations within the same inter‐laboratory program, 60 matched isolated erythrocyte or liquid whole blood specimens were tested at three laboratories. Laboratories measured PEth by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS), two using isolated erythrocytes, while the third used liquid whole blood, which underwent haematocrit correction before comparison with isolated erythrocyte PEth concentrations. There was acceptable consensus (87%) among laboratories to detect PEth around a cut‐off of 35 μg/L of erythrocytes. Each laboratory correlated well with the group average PEth concentration (R > 0.98) for each specimen above the cut‐off. Differences were observed between laboratories in bias, which did not affect comparable sensitivity at the selected cut‐off. This work demonstrates the feasibility of an inter‐laboratory comparison for erythrocyte PEth analysis across different LC‐MS/MS methodologies and different blood preparations. [ABSTRACT FROM AUTHOR]

Phosphatidylethanol (PEth) is a sensitive and specific biomarker of alcohol consumption in the prior 2-3 weeks. Standard, manual PEth testing using dried blood spots (DBS) is a multi-step time-consuming process. A novel, automated processing and testing method has been developed to decrease DBS processing and testing time. We conducted automated testing, using regioisomerically pure PEth reference material, on randomly selected DBS, which had previously been tested via manual methods and then stored for 3-6 years at -80 °C, to compare the results (PEth 16:0/18:1 homologue). We chose samples for re-testing using categories found in the literature as follows: 1) PEth 200-1000 ng/mL; 4) PEth >1000 ng/mL. We calculated agreement between the categories using the weighted kappa statistic (n = 49 DBS). We quantified agreement between continuous measures using the intraclass correlation coefficient (ICC), and further described the relationship between variables using Spearman correlation. The median PEth result was 155 ng/mL (interquartile range [IQR]: 1-1312 ng/mL) via automated methods and 98.8 ng/mL (IQR: 10.2-625.0 ng/mL) via manual methods. The weighted kappa comparing the automated to manual PEth results was 0.76 [95% Confidence Interval (CI): 0.66-0.86]. The ICC was 0.69 (95% CI: 0.54-0.79), and the Spearman correlation was 0.98 (95% CI: 0.95-0.99). While the new methods yielded somewhat higher PEth values, we found good to excellent agreement between clinically relevant PEth categories. Automated DBS processing and testing using new reference standards are promising methods for PEth testing.

BackgroundThe risk of tuberculosis (TB) is high among people with HIV (PWH). Heavy alcohol drinking independently increases TB risk and approximately 25% of PWH globally engage in heavy drinking. While isoniazid (INH) preventive therapy decreases TB incidence and mortality among PWH, heavy drinking during INH is associated with liver toxicity and poor adherence. Interventions are, therefore, urgently needed to decrease alcohol use and improve adherence to INH in this population in settings with high prevalence of HIV and TB like Uganda.MethodsThe Drinkers' Intervention to Prevent TB (DIPT) study is a 2×2 factorial randomized controlled trial among HIV/TB co-infected adults (≥18 years) who engage in heavy alcohol drinking and live in Uganda. The trial will allocate 680 participants with a 1:1:1:1 individual randomization to receive 6 months of INH and one of the following interventions: (1) no incentives (control), (2) financial incentives contingent on low alcohol use, (3) financial incentives contingent on high adherence to INH, and (4) escalating financial incentives for both decreasing alcohol use and increasing adherence to INH. Incentives will be in the form of escalating lottery-based monetary rewards. Participants will attend monthly visits to refill isoniazid medications, undergo liver toxicity monitoring, and, except for controls, determine eligibility for prizes. We will estimate (a) the effect of incentives contingent on low alcohol use on reduction in heavy drinking, measured via a long-term objective and self-reported metric of alcohol use, at 3- and 6-month study visits, and (b) the effect of incentives contingent on high adherence to INH, measured as >90% pill-taking days by medication event monitoring system cap opening. We will use qualitative methods to explore the mechanisms of any influence of financial incentives on HIV virologic suppression.DiscussionThis study will provide new information on low-cost strategies to both reduce alcohol use and increase INH adherence among people with HIV and TB infection who engage in heavy drinking in low-income countries with high HIV and TB prevalence.Trial registrationClinicalTrials.gov NCT03492216 . Registered on April 10, 2018.

Aims Phosphatidylethanol (PEth) is only formed when ethanol is present in blood. This direct alcohol marker has been widely discussed, including the minimum amount of ethanol being necessary to form as much PEth as to exceed the threshold of 20 ng/mL in previously PEth negative subjects. In order to corroborate hitherto existing results, a drinking study including 18 participants after a 3-week alcohol abstinence was performed. Methods They consumed a pre-calculated amount of ethanol to reach a blood alcohol concentration (BAC) of at least 0.6 g/kg. Blood was drawn before and periodically seven times after alcohol administration on day 1. Blood and urine were also collected the next morning. Dried blood spots (DBS) were prepared immediately from collected venous blood. BAC was determined by head space gas chromatography and the concentrations of both PEth (16:0/18:1, 16:0/18:2 and five additional homologues) and ethyl glucuronide (EtG) were analysed using liquid chromatography–tandem mass spectrometry. Results Out of 18, 5 participants had concentrations of PEth 16:0/18:1 above the threshold of 20 ng/mL, and 11 out of the 18 subjects had concentrations between 10 and 20 ng/mL. In addition, four persons had PEth 16:0/18:2 concentrations above 20 ng/mL the following morning. All test subjects tested positive for EtG in DBS (≥ 3 ng/mL) and urine (≥100 ng/mL) upon 20–21 h after alcohol administration. Conclusion By combining both a lower cutoff of 10 ng/mL and the homologue PEth 16:0/18:2, the sensitivity to detect a single alcohol intake after a 3-week abstinence increases to 72.2%. [ABSTRACT FROM AUTHOR]

Phosphatidylethanol (PEth) are membrane molecules formed from phosphatidylcholine and ethanol through transphosphatidylation catalyzed by phospholipase D. Measurement of the main PEth form 16:0/18:1 is used as a specific and sensitive alcohol biomarker, since its formation requires ethanol, it accumulates in the blood upon repeated ethanol exposure, and it is only slowly eliminated during abstinence. PEth formation correlates with alcohol intake at the population level, albeit with considerable inter-individual variation as for the half-life during withdrawal. Over the past decade, the use of PEth has increased significantly and the applications have broadened. In Sweden, routine decision limits and the interpretation of test results for PEth were harmonized in 2013, using < 0.05 µmol/L (∼35 µg/L) as the recommended lower reporting limit and values > 0.30 µmol/L (∼210 µg/L) to indicate regular high alcohol intake. Routine test results show a large variation with about half being < 0.05 µmol/L and some even exceeding 10 µmol/L. In 2013, an external quality assessment (EQA) scheme for PEth 16:0/18:1 measurement in whole blood was also started (Equalis, Uppsala, Sweden), presently involving 56 laboratories from 13 countries. The agreement of PEth results between the laboratories has gradually improved to a CV < 15%. The current clinical and scientific information suggests that PEth values below the lower reporting limit (typically ∼0.03–0.05 µmol/L, or ∼20–35 µg/L) indicates sobriety or only low or occasional alcohol consumption, while regular high alcohol intake at levels corresponding to harmful drinking is required in most cases to reach PEth values > 0.30 µmol/L. [ABSTRACT FROM AUTHOR]

Introduction: Detection of alcohol (ETOH) use with biomarkers provides an opportunity to intervene and treat patients with alcohol use disorder before and after liver transplant (LT). We describe our center's experience using urine ethyl glucuronide (EtG) and serum phosphatidylethanol (PEth) in alcohol screening protocols. Methods: Single‐center, retrospective review of patients presenting for LT evaluation, patients waitlisted for LT for alcohol‐associated liver disease (ALD), and patients who received a LT for ALD over a 12‐month period, from October 1, 2019 through September 30, 2020. Patients were followed from waitlisting to LT, or for up to 12 months post‐LT. We monitored protocol adherence to screening for ETOH use‐ defined as completion of all possible tests over the follow‐up period‐ at the initial LT visit, while on the LT waitlist and after LT. Results: During the study period, 227 patients were evaluated for LT (median age 57 years, 58% male, 78% white, 54.2% ALD). Thirty‐one patients with ALD were placed on the waitlist, and 38 patients underwent LT for ALD during this time period. Protocolized adherence to screening for alcohol use was higher for PEth for all LT evaluation patients (191 [84.1%] vs. 146 [67%] eligible patients, p <.001), in patients with ALD waitlisted for LT (22 [71%] vs. 14 (48%] eligible patients, p =.04) and after LT for ALD, 20 (33 [86.8%] vs. 20 [52.6%] eligible patients, p <.01). Few patients with a positive test in any group completed chemical dependency treatment. Conclusions: When screening for ETOH use in pre‐ and post‐LT patients, protocol adherence is higher using PEth compared to EtG. While protocolized biomarker screening can detect recurrent ETOH use in this population, engagement of patients into chemical dependency treatment remains challenging. [ABSTRACT FROM AUTHOR]

BackgroundObjective measurement of alcohol consumption is important for clinical care and research. Adjusting for self-reported alcohol use, we conducted an individual participant data (IPD) meta-analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self-reporting unhealthy alcohol consumption.MethodsWe identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1-step IPD meta-analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index-BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger-prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self-reported alcohol use using the AUDIT-C score.ResultsOne third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT-C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables.ConclusionsAmong people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.

BackgroundDirect biomarkers such as phosphatidylethanol (PEth) have the capability to detect heavy alcohol use, but it is unclear how strongly self-reported reduction in alcohol use correlates with reduction in PEth. We sought to explore the strength of correlation between reductions in self-reported alcohol use and change in PEth among a sample of women living with HIV (WLWH) who participated in a clinical trial to reduce heavy alcohol use. We also sought to determine whether this correlation was stronger in women with lower body mass index (BMI) and women without an alcohol use disorder (AUD).Methods81 WLWH (mean age = 48.7, 80% Black) engaging in a randomized trial of naltrexone versus placebo with a positive baseline PEth (≥8 ng/ml), and alcohol use data at baseline, 2, and 7 months were included in this analysis. Spearman correlation coefficients were compared to measure the correlation between baseline PEth and number of drinks per week by demographic, biological, and alcohol use factors. Mini-International Neuropsychiatric Interview was used to screen for AUD. Further analyses were stratified by BMI and AUD. Spearman correlation coefficients were calculated for the change in PEth and the change in number of drinks per week over 7 months, including 3 time-points: baseline, 2, and 7 months.ResultsAt baseline, the correlation between baseline PEth and the number of drinks per week was significantly stronger for those with a BMI ≤25 compared to those with a BMI > 25 (r = 0.66; r = 0.26, respectively). Similarly, the correlation between baseline PEth and number of drinks was stronger for those who did not screen positive for AUD compared with those who did (r = 0.66; r = 0.25, respectively). When stratifying by BMI, a low-to-moderate correlation (r = 0.32, p = 0.02) was present for persons with a BMI > 25; when stratifying by AUD, a moderate correlation (r = 0.50, p

Background: The free‐access (FA) intravenous alcohol self‐administration (IV‐ASA) paradigm is an experimental approach that can identify modulators of alcohol consumption in humans. Moreover, the outcome measures of IV‐ASA paradigms are associated with self‐reported alcohol intake using the timeline follow‐back method (TLFB). To evaluate how FA IV‐ASA reflects drinking in real life, we examined the relationship between an objective marker of recent alcohol intake, phosphatidylethanol in blood (B‐PEth), and TLFB and measures obtained during IV‐ASA in individuals with alcohol use disorder (AUD) and social drinkers (SD). We also explored the associations between these measures and gut‐brain peptides involved in AUD pathophysiology. Methods: Thirty‐eight participants completed a laboratory session in which they self‐administered alcohol intravenously. The safety limit was 200 mg%, and main outcomes were mean and peak breath alcohol concentrations (BrAC). Blood samples were drawn prior to IV‐ASA and subjective alcohol effects were rated during the experiment. Results: The study sample comprised 24 SD and 14 participants with DSM‐5 mild AUD. Although BrACs were not associated with B‐PEth or TLFB in the full sample or AUD subgroup, there was an association with TLFB in SD. In both subgroups, BrACs were associated with alcohol craving but with differential timing. Total ghrelin levels were higher in AUD participants than in SD. Conclusions: No associations between B‐PEth levels and achieved BrACs were observed in the mild AUD group, the SD group, or the full sample. The ability for FA IV‐ASA to reflect recent drinking was confirmed only for TLFB in SD, whereas there were no associations within the smaller subsample of participants with mild AUD or in the full sample. Further studies that include a larger AUD sample are warranted. The association of BrACs with craving for alcohol suggests that the IV‐ASA method may be useful for assessing interventions that target craving. This could be explored by using the FA IV‐ASA model to evaluate the effects on craving of approved pharmacotherapies for AUD. [ABSTRACT FROM AUTHOR]

Background: Phosphatidylethanol (PEth) is a biomarker for recent alcohol consumption that would ideally validate self‐reported alcohol consumption behaviors. We assessed the relationship between PEth and several self‐reported alcohol consumption metrics among hazardous alcohol users living with HIV in Vietnam. Methods: Participants in a three‐arm randomized controlled trial assessing two alcohol interventions reported recent alcohol consumption on a 30‐day timeline follow‐back interview and had a PEth assessment at enrollment, 3 months, and 12 months of the study follow‐up. We examined the relationship between self‐reported alcohol consumption and quantitative PEth results using Spearman rank correlation and receiver‐operating characteristic (ROC) curves to calculate the area under the curve (AUC). We assessed associations between categorical PEth results and self‐reported drinking behaviors using prevalence ratios calculated with regression models and generalized estimating equations. Results: Among 1221 study visits (n = 439 participants; 425 (97%) men), the median PEth result was 71 ng/mL (Interquartile range (IQR): 20, 212), and participants reported a median of 11 (IQR: 4, 24) drinking days and 25 (IQR: 8, 71) standard drinks in the previous 28 days. Quantitative PEth results were moderately correlated with drinking days (ρ = 0.26–0.35) and standard drinks consumed (ρ = 0.23–0.38) in the same period. AUCs ranged from 0.54 (any binge drinking in the past 28 days) to 0.82 (any alcohol consumed in the past 21 days). Positive PEth results (≥50 ng/mL) were 2.24 (95% Confidence Interval [CI]: 1.49, 3.35) times as prevalent among participants who reported drinking in the previous 28 days compared with those who did not. Conclusions: Although PEth values and self‐reported alcohol use were correlated, the observed associations were modest. Additional research into the dynamics of PEth production and elimination is warranted across diverse populations to better understand how PEth assessments can best be integrated into research and clinical care. [ABSTRACT FROM AUTHOR]

BACKGROUND:Alcohol use is common among people living with HIV and particularly harmful during pregnancy. However, objective data on alcohol use in pregnant women living with HIV (WLWH) are lacking. In areas with high levels of alcohol use generally, such as South Africa and Uganda, these data are needed to inform interventions. METHODS:Pregnant and nonpregnant, antiretroviral therapy-naive WLWH were recruited from outpatient clinics in South Africa and Uganda. Women provided self-report data on previous three-month alcohol use and potential mental health correlates of alcohol use (depression and stigma). Blood samples were used to measure phosphatidylethanol (PEth), an objective biomarker of recent alcohol intake. We analyzed any alcohol use (ie, any self-reported use or PEth-positive [≥8 ng/mL]) and under-reporting of alcohol use (ie, no self-reported use with concurrent PEth-positive). RESULTS:Among pregnant WLWH (n = 163, median age was 26 [interquartile range: 23-29], median gestational age was 20 weeks [interquartile range: 16-26]), 40% were using alcohol and 16% under-reported alcohol use. Neither any alcohol use nor under-reporting of alcohol use differed significantly between pregnant and nonpregnant women or by country (P > 0.05). Greater depression (but not greater stigma) was significantly associated with any alcohol use (adjusted odds ratio = 1.41, 95% confidence interval: [1.01 to 1.99]; P = 0.045). CONCLUSIONS:Alcohol use was prevalent and under-reported among pregnant WLWH in South Africa and Uganda, similar to nonpregnant participants, and associated with depression. General health care and antenatal clinic settings present opportunities to provide integrated alcohol-based counseling and depression treatment.

BackgroundSelf-report is widely used to assess alcohol use in research and clinical practice, but may be subject to social desirability bias. We aimed to determine if social desirability impacts self-reported alcohol use.MethodsAmong 751 human immunodeficiency virus (HIV)-infected patients from a clinic in southwestern Uganda, we measured social desirability using the Marlowe-Crowne Social Desirability Scale (SDS) Short Form C, self-reported alcohol use (prior 3 months) Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), and phosphatidylethanol (PEth), a biomarker of prior 3 weeks' drinking. We conducted multiple regression analyses to assess the relationship between SDS score (low, medium, and high levels) and (i) any self-reported recent alcohol use, among those who were PEth-positive (≥8 ng/ml), and (ii) continuous AUDIT-C score, among those reporting any recent alcohol use. We controlled for PEth level, age, gender, education, economic assets, marital status, religion, spirituality/religiosity, social support, and study cohort.ResultsOf 751 participants, 59% were women; the median age was 31 years (interquartile range [IQR]: 26 to 39). Median SDS score was 9 (IQR: 4 to 10). Two-thirds (62%) self-reported any recent alcohol use; median AUDIT-C was 1 (IQR: 0 to 4). Among those who were PEth-positive (57%), 13% reported no recent alcohol use. Those with the highest SDS tertile had decreased odds of reporting any recent alcohol use compared to the lowest tertile, but the association did not reach statistical significance in multivariable analyses (adjusted odds ratio 0.55 [95% confidence interval (CI): 0.25, 1.23]). Among participants self-reporting recent alcohol use, SDS level was negatively associated with AUDIT-C scores (adjusted β: -0.70 [95% CI: -1.19, -0.21] for medium vs. low SDS and -1.42 [95% CI: -2.05, -0.78] for high vs. low SDS).ConclusionsWhile use of objective measures (e.g., alcohol biomarkers) is desirable for measuring alcohol use, SDS scores may be used to adjust self-reported drinking levels by participants' level of social desirability in HIV research studies.

Aims to investigate the relationship between phosphatidylethanol (PEth) and withdrawal severity in patients with alcohol use disorder (AUD). Methods in 34 patients with AUD admitted for treatment of acute alcohol withdrawal, data were available for initial blood PEth concentrations and scores throughout detoxification of symptoms of withdrawal assessed by trained medical staff using the alcohol withdrawal syndrome (AWS)-scale, a validated scale consisting of 11 items in the alcohol withdrawal syndrome (two subscales with seven physiological and five psychological symptoms). Results a significant positive correlation between PEth and the severity of alcohol withdrawal was found. When the sample was divided into two groups, according to whether or not AWS score at some point in the treatment reached 6 or more, the median PEth score was higher in those whose peak score had been 6 or more (score of 6 being the suggested cutoff to start medicating the withdrawal syndrome). Although there was a trend for some aspects of the clinical history to be more 'severe' in those with higher AWS, no differences reached significance. Conclusion blood PEth on admission could have a role in identifying patients at risk of more severe AWS. [ABSTRACT FROM AUTHOR]

ObjectiveTo establish the ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method to detect ethanol metabolites phosphatidylethanol （PEth） in whole blood.MethodsAn appropriate amount of aqueous solution including 1% formic acid was added to 100 μL whole blood, the protein was precipitated with acetone, centrifuged and the supernatant was purified and enriched by using Bond Elut Certify column. The eluent was redissolved with 1/1 isopropanol/acetonitrile （v/v） solution after nitrogen blowing and then tested by UPLC-MS/MS. Selective reaction monitoring scanning was carried out in negative ionization mode, and quantitative analysis was performed by external standard method.ResultsPEth showed a linear relationship over the concentration range of 1-160 ng/mL in whole blood （r=0.999 9） with peak area. The detection limit was 0.2 ng/mL, the quantification limit was 1 ng/mL, the recovery rate was 97.43%-103.61%, the accuracy was 0.99%-1.77%, the intra-day precision was 0.4%-2.4%, and the inter-day precision was 1.1%-3.3%, and the matrix effect was 91.00%-99.55%. PEth was not detected in the in vitro blood samples supplemented with ethanol. PEth was detected positive in three drunk driving cases, and the concentration were 195.49， 83.67 and 876.12 ng/mL, respectively.ConclusionThe established method has high sensitivity and specificity and the analysis results are accurate. It is suitable for the qualitative and quantitative analysis of PEth in whole blood.

Suicide is a complex transdiagnostic phenomenon. It is strongly associated with, but not exclusive to major depressive disorder (MDD). Hazardous alcohol drinking has also been linked to an increased risk of suicidal behaviours, however, it is often underreported. The study aimed to evaluate whether an objective measure of chronic alcohol use, phosphatidylethanol (PEth) could be useful as a biomarker in clinical practice. ology. The present case-control multi-centric study recruited 156 participants into three study groups: 52 patients treated for major depressive disorder (MDD), 51 individuals immediately following a suicide attempt (SA), and 53 volunteers. Sociodemographic data, medical history, and laboratory data, including PEth concentrations and C-reactive protein levels, were collected from study participants. PEth concentrations were the highest in suicide attempters (232,54 ± 394,01 ng/ml), followed by patients with MDD (58,39 ± 135,82 ng/ml), and the control group (24,45 ± 70,83 ng/ml) (Kruskall Wallis χ 2 = 12.23, df = 2, p =.002). In a multinomial logistic regression model with adjustments, PEth concentration was able to predict belonging to suicide attempters' group, but not to depression group (p =.01). Suicide attempters were also more likely to underreport their recent alcohol consumption. We did not analyze SA methods, psychiatric comorbidity and several other factors that might be associated with PEth levels, such as body mass index, race, and haemoglobin levels. Sample recruited in hospital settings may not be representative of the whole population. The results of this adult-only study cannot be generalized to adolescents. PEth levels in recent suicide attempters significantly exceeded those of patients with MDD and controls. Suicide attempters also were more likely to underreport their alcohol consumption when questioned about their consuption. PEth might be an interesting biomarker to evaluate individuals at risk of SA. • Phosphatidylethanol (PEth) levels are significantly increased in psychiatric patients compared with controls. • PEth levels in suicide attempters was the highest and significantly higher than in patients with major depressive disorders. • There was a discrepancy between self-reported chronic alcohol use and objectively measured alcohol use in suicide attempters. • Low grade inflammation was implicated in the PEth association with suicide attempt and major depressive disorder. • PEth levels predicted depression and suicidality scores only in suicide attempter group. [ABSTRACT FROM AUTHOR]

Aims: Falsely lower or even negative phosphatidylethanol (PEth) levels may theoretically be seen in patients with haemolytic diseases, and the present study aimed to elucidate this hypothesis. Methods: PEth and carbohydrate‐deficient transferrin (CDT) from 9893 serum and whole blood samples were included along with markers of haemolysis (i.e. haptoglobin, HbA1c, reticulocytes, LD and Hb). Cases showing discrepancy between PEth and CDT, that is, a low PEth value and a high CDT value, were considered to be possibly caused by falsely lowered PEth despite high alcohol consumption. These cases (N = 233) were compared to the control group without PEth and CDT mismatch. Results: The levels of haptoglobin were significantly lower in the cases showing low PEth and high CDT (estimate = −0.62, p = 0.002). The levels of HbA1c (estimate = −3.26, p = 0.001) and Hb (estimate = −0.507, p < 0.001) were also significantly lower in this group. These findings indicate haemolytic diseases in the low PEth/high CDT group. There were no significant differences for reticulocytes and LD concentrations between the low PEth/high CDT group and the control group. Conclusions: These results indicate that falsely low PEth values could be associated with markers of haemolytic diseases, although more research is needed to highlight this further. [ABSTRACT FROM AUTHOR]

Background: Unhealthy alcohol use is associated with increased progression to tuberculosis (TB) disease, but its effect on adherence to isoniazid (INH) preventive therapy is not known. Methods: This was a prospective study of persons with HIV with latent TB in southwestern Uganda reporting any current (previous 3 months) alcohol use or no alcohol consumption in the previous year (2:1 ratio). All received INH. We defined suboptimal adherence as <90% of days with at least 1 Medication Event Monitoring System cap opening, over the previous 90 days. Alcohol use was categorized as follows: none: no self-report and phosphatidylethanol (PEth) <8 ng/mL; moderate: Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) 1–2 (women) or 1–3 (men) and/or PEth 8 ≥ 50 ng/mL; and unhealthy: AUDIT-C ≥3 (women) or ≥4 (men) and/or PEth ≥50 ng/mL. We used generalized estimating equation logistic regression analyses to assess the association between the level of alcohol use and suboptimal INH adherence. Results: Three hundred two persons were enrolled; 279 were on INH for 3 or more months. The prevalence of suboptimal INH adherence was 31.3% at 3 months and 43.9% at 6 months. The odds of suboptimal INH adherence were higher for unhealthy (adjusted odds ratio, 2.78; 95% confidence interval: 1.62 to 4.76) and moderate (adjusted odds ratio, 1.59; 95% confidence interval: 0.94 to 2.71) compared with no alcohol consumption. Conclusions: Suboptimal adherence to INH at 3 and 6 months was high among prospective study of persons with HIV and associated with unhealthy alcohol use. Adherence support and alcohol reduction strategies are needed for this group at high risk for active TB. [ABSTRACT FROM AUTHOR]

Introduction. The diagnosis of alcohol-related liver disease is limited by the lack of a tool to reliably identify whether the present deterioration in the patient’s condition is due to alcohol consumption or other causes.Purpose. to conduct a comparative assessment of the clinical and diagnostic significance of liver function biochemical indicators (AST, ALT, GGT, ALP) and their calculated derivatives (AST/ALT, GGT/ALP, GGT/GGTn, ALP/ALPn) as markers of alcohol consumption in patients with alcoholic liver cirrhosis.Material and methods. The observational study included 112 men over 18 years of age with alcohol-related liver cirrhosis. The patients were assessed the severity of liver cirrhosis according to the Child-Pugh scale, performed general and biochemical blood tests, coagulation test, assessment of the fact of alcohol consumption by the level of phosphatidylethanol. An analysis was made of the relationship between alcohol consumption and changes in laboratory parameters of liver function, with the determination of their sensitivity and specificity.Results. Patients with Child-Pugh B cirrhosis who consumed alcohol on phosphatidylethanol had higher levels of plasma albumin, GGT, and lower values of creatinine, direct and total bilirubin, urea, and aPTT compared with patients who did not drink alcohol (p < 0.05). Alcohol-drinking patients with class C cirrhosis have higher ALT levels compared with abstinent patients with the same severity of cirrhosis (p < 0.05). The relationship between the fact of alcohol consumption, determined by the level of phosphatidylethanol, and the ratio of GGT of patients to the normal GGT value, as well as between the ratio of GGT to alkaline phosphatase and the degree of increase in GGT, turned out to be statistically significant. To assess the fact of alcohol consumption, the level of serum GGT > 65 IU/ l (75.5%) has the highest sensitivity, the highest specificity is the ratio of the patient’s GGT to the normal value of GGT > 2 (82.9%).Conclusion. Compared with the known 100% sensitivity and > 92% specificity of Peth as a alcohol biomarker, among the biochemical indicators of liver function and their calculated derivatives, GGT > 65 IU/l have the greatest sensitivity or specificity (respectively, 75.5% and 65%) and GGTnorm. > 2 (37.7% and 82.9%, respectively), which makes it possible to use the totality of these parameters as an indicator of the continued impact on the patient of the main etiological factor of alcohol-related liver cirrhosis in the routine practice of most medical organizations of the Russian Federation.

Abstract Background The use of standard screening methods could improve the detection rate of unhealthy alcohol use in patients admitted to psychiatric acute and emergency departments. The aim of the present study was to investigate the ability of the alcohol biomarker phosphatidylethanol (PEth) to identify patients with high levels of alcohol consumption prior to admission. Methods The data were prospectively collected at admittance to an acute psychiatric department in the period January 2016 to June 2017. A blood sample for the analysis of PEth was available from 177 patients. We compared the PEth concentrations with the Alcohol Use Disorders Identification Test (AUDIT) scores during the hospital stay, and psychiatric diagnoses at discharge. Results A total of 45.8% of the patients had a PEth concentration ≥ 0.03 μmol/L, indicating significant alcohol consumption. AUDIT scores consistent with unhealthy alcohol use were present in 51.7%. There was a significant positive correlation between PEth concentrations and AUDIT scores (r = 0.631, p

HIV and alcohol use are two serious and co-existing problems in sub-Saharan Africa. We examined the relationship between spirituality and/or religiousness (SR) and unhealthy alcohol use among treatment-naïve HIV-infected adults attending the HIV clinic in Mbarara, Uganda. Unhealthy alcohol was defined as having either an alcohol use disorders identification test-consumption score of ≥4 for men or ≥3 for women, or having a phosphatidylethanol level of ≥50 ng/ml based on analysis of dried bloodspot specimens. Of the 447 participants, 67.8% were female; the median age was 32 years (interquartile range [IQR] 27-40). About half reported being Protestant (49.2%), 35.1% Catholic, and 9.2% Muslim. The median SR score was high (103 [IQR 89-107]); 43.3% drank at unhealthy levels. Higher SR scores were associated with lower odds of unhealthy drinking (adjusted odds ratio [aOR]: 0.83 per standard deviation [SD] increase; 95% confidence interval [CI] 0.66-1.03). The "religious behavior" SR subscale was significantly associated with unhealthy alcohol use (aOR: 0.72 per SD increase; 95% CI 0.58-0.88). Religious institutions, which facilitate expression of religious behavior, may be helpful in promoting and maintaining lower levels of alcohol use.

BackgroundAlcohol use has been shown to accelerate disease progression in experimental studies of simian immunodeficiency virus in macaques, but the results in observational studies of HIV have been conflicting.MethodsWe conducted a prospective cohort study of the impact of unhealthy alcohol use on CD4 cell count among HIV-infected persons in southwestern Uganda not yet eligible for antiretroviral treatment (ART). Unhealthy alcohol consumption was 3-month Alcohol Use Disorders Identification Test-Consumption positive (≥3 for women, ≥4 for men) and/or phosphatidylethanol (PEth-an alcohol biomarker) ≥50 ng/mL, modeled as a time-dependent variable in a linear mixed effects model of CD4 count.ResultsAt baseline, 43% of the 446 participants were drinking at unhealthy levels and the median CD4 cell count was 550 cells/mm (interquartile range 416-685). The estimated CD4 cell count decline per year was -14.5 cells/mm (95% confidence interval: -38.6 to 9.5) for unhealthy drinking vs. -24.0 cells/mm (95% confidence interval: -43.6 to -4.5) for refraining from unhealthy drinking, with no significant difference in decline by unhealthy alcohol use (P value 0.54), adjusting for age, sex, religion, time since HIV diagnosis, and HIV viral load. Additional analyses exploring alternative alcohol measures, participant subgroups, and time-dependent confounding yielded similar findings.ConclusionUnhealthy alcohol use had no apparent impact on the short-term rate of CD4 count decline among HIV-infected ART naive individuals in Uganda, using biological markers to augment self-report and examining disease progression before ART initiation to avoid unmeasured confounding because of misclassification of ART adherence.

BackgroundPhosphatidylethanol (PEth) is a direct biomarker for alcohol that is formed shortly after alcohol use and may remain detectable in blood for weeks after alcohol consumption. There is little research on alcohol use factors that influence PEth elimination, especially among women.MethodsData were collected from 116 alcohol use-disordered women who were recently incarcerated. We used a 2-part model with logistic and linear components to examine whether alcohol consumption in the 2 weeks prior to incarceration and days since last alcoholic drink (operationalized as abstinence days prior to incarceration + days incarcerated) were associated with PEth detectability (>8 ng/ml) and level (ng/ml) in blood.ResultsParticipants reported drinking an average of 10 drinks per day in the 2 weeks prior to incarceration. Days since last drink was negatively associated with PEth level (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.93; 0.99) and being PEth detectable (OR = 0.96, 95% CI = 0.91; 0.99). Quantity of alcohol consumed prior to jail admission was associated with PEth detection (OR = 1.08; 95% CI = 1.03; 1.16), but not PEth level.ConclusionsDays since last alcoholic drink and drinks per day both influenced PEth detectability, but only days since last drink predicted PEth level among a large sample of women with alcohol use disorder in the criminal justice system.

BackgroundUnhealthy alcohol use may be particularly detrimental among individuals living with HIV and/or hepatitis C virus (HCV), and is often under-reported. Direct biomarkers of alcohol exposure may facilitate improved detection of alcohol use.MethodsWe evaluated the association of alcohol exposure determined by both self-report [Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)] and a direct biomarker [phosphatidylethanol (PEth)], with mortality among HIV-infected and HIV-uninfected in the Veterans Aging Cohort Study-Biomarker Cohort. We considered PEth

BackgroundBiomarkers can play a key role in supplementing self-report information in alcohol research. In this study, we examined phosphatidylethanol (PEth) in comparison with self-reported alcohol use over time in a randomized controlled trial.MethodsParticipants were women living with HIV enrolled in a randomized placebo-controlled trial of naltrexone for reducing hazardous drinking. Drinking behavior was measured using Timeline Followback (TLFB), and PEth as a biomarker using dried blood spots. Data collected at baseline, and months 2 and 7 were analyzed. In addition to calculated Spearman's correlations, mixed-effects modeling was used to evaluate the changes in self-reported drinking and PEth, respectively, adjusting for body mass index (BMI).ResultsA total of 194 participants (83% black, mean age 48) were included in the analysis. PEth levels were significantly correlated with self-reported drinking via TLFB, Spearman's r = 0.21 at baseline, r = 0.29 at 2 months, and r = 0.28 at 7 months, respectively. No demographic or health factors, except for BMI, was associated with whether self-report was consistent with PEth. Mixed-effects model indicated that self-reported drinking showed significantly greater reductions in the naltrexone treatment group than the placebo group at the 2- and 7-month visits, whereas PEth measure only showed this difference at the 7-month follow-up.ConclusionsThe magnitude of the correlation between PEth and self-reported alcohol consumption was small. Caution is needed when using either self-report or PEth as a sole outcome measure for alcohol behavior changes in clinical trials.

Background: Antiretroviral therapy has improved life expectancy among people living with HIV (PLWH). Despite increased longevity, PLWH are at increased risk of age‐related comorbidities, including frailty. We examined the relationship between body composition and frailty among PLWH, and moderation of this relationship by substance use, physical activity (PA), and physical function. Methods: Participants (n = 341; 71% male, 48 ± 10 years, body mass index (BMI) = 27.3 ± 7.0 kg/m2) enrolled in the New Orleans Alcohol Use in HIV (NOAH) study underwent measures of body composition, muscle strength, and gait speed. Whole blood phosphatidylethanol (PEth) was measured, and substance use and PA were self‐reported. Frailty risk measures included the 58‐Item Deficit Index (DI58) and the Veterans Aging Cohort Study (VACS) Index 1.0, where higher scores indicate greater frailty risk. Results: Multivariable linear regression adjusted for age, sex, and race showed that higher fat‐free mass index (FFMI), body fat (%), waist‐to‐hip ratio, and body mass index (BMI) ≥ 25.0 kg/m2 vs. < 25.0 kg/m2 were significantly (p < 0.05) associated with decreased frailty risk measured by the VACS Index, whereas adjusted analyses showed no association between body composition variables and the DI58 score. Recent alcohol use, muscle strength, and PA, but not lifetime alcohol use or gait speed, significantly moderated associations between body composition variables and frailty risk with medium‐to‐large effect sizes. Subgroup analyses revealed a negative relationship between DI58 and FFMI among people with PEth > 8 ng/ml and negative relationships of VACS Index with FFMI and WHR in people with lower muscle strength. Overweight or obese BMI categories were positively associated with DI58 in people with lower muscle strength or higher PA level but negatively associated in those with higher muscle strength. Conclusions: Our findings indicate that body composition has significant modulatory effects on frailty risk in PLWH, where obesity increases the risk of frailty and greater muscle mass may be protective, even in individuals who use alcohol. These results highlight the importance of considering body composition, physical activity, and physical function in assessing frailty risk in PLWH, particularly among individuals who use alcohol. Moreover, they support the implementation of physical activity interventions to ameliorate the risk of frailty in aging PLWH. [ABSTRACT FROM AUTHOR]

The role of phosphatidylethanol (PEth) as an alcohol consumption marker is increasing in clinical and forensic medicine. During the COVID-19 pandemic, the role of hygiene increased, and it became common practice to use disinfectants almost everywhere. This paper highlights a possible source of false positive results (by the vapors of alcohols during the blood spot drying process) in dried blood spots (DBS) by LC-MS/MS quantitation of PEth. To achieve this, the PEth quantitation method was validated according to FDA guidelines. Additionally, the synthesis of phosphatidyl derivatives by phospholipase D (PLD) in the presence of methanol and 2-propanol vapors during the DBS process was determined. Each PEth-negative sample from a healthy male patient incubated in the presence of ethanol vapor becomes PEth-positive. After 4 h of DBS drying, teetotalers become "moderate drinkers". It is necessary to avoid using alcohol-containing disinfectants in treatment rooms, where DBS is sampled. [ABSTRACT FROM AUTHOR]

Background: Alcohol-related liver disease (ALD) is the leading indication for liver transplantation in the United States. The aim of this study was to describe the impact of phosphatidylethanol (PEth) in the surveillance for alcohol use after liver transplantation., Methods: We conducted a single-center retrospective study to assess the impact of phosphatidylethanol (PEth) for the surveillance of alcohol use and its correlation to health outcomes. We compared orthotopic liver transplant (OLT) recipients for ALD transplanted between 2016 and 2018, before the introduction of PEth, to those transplanted between 2019 and 2022, after the introduction of PEth. Alcohol relapse versus nonrelapse cohorts were also compared. Follow-up time for all cohorts was limited to 3 years post-OLT. Continuous variables were analyzed with an independent t-test and categorical variables with Fischer's exact test and chi-square test. The Kaplan-Meier method and log-rank test were used to assess alcohol-free survival., Results: We reviewed 263 patients who were transplanted for ALD; 46 (17.5%) patients were noted to have at least one episode of alcohol relapse after their transplant. Patients with alcohol relapse had more frequent episodes of elevated liver enzymes compared with nonrelapsed patients (4.35 episodes vs. 2.46 episodes respectively, p < 0.001). The number of hospitalizations was also noted to be elevated among relapsed versus nonrelapsed patients; however, this was not statistically significant (2.85 vs. 2.50 respectively, p = 0.307). When comparing relapse rates before and after the introduction of PEth, relapses were notably detected more frequently after the introduction of PEth (17% vs. 7%, p = 0.012). No difference was noted in rates of mortality between patients who did or did not relapse., Conclusions: Overall, PEth is an effective surveillance tool in the postliver transplant population to monitor for alcohol relapse. Early detection of relapse can lead to opportunities for early intervention to avoid alcohol-related complications., (© 2024 The Author(s). Alcohol, Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.)

Alcohol biomarkers can monitor both recent and long-term drinking and provide information about drinking habits as a complement to self-reporting. Ethyl glucuronide (EtG) and phosphatidylethanol (PEth) are the most sensitive available biomarkers for this purpose. The present study aimed to collect data on both PEth and EtG in the same blood sample, in addition to ethanol, in order to evaluate the combined use of these biomarkers. Venous EDTA blood samples (n = 1149) sent to the laboratory as part of a clinical routine service for measuring PEth were investigated. PEth and EtG concentrations were analyzed using liquid chromatography–mass spectrometry methods and ethanol with an enzymatic method. Of the 1149 samples, 95 were positive for ethanol (range 0.11–3.12 g/L), 454 for EtG (1.0–9739 ng/mL), 635 for PEth (0.014–6.0 µmol/L), 534 for PEth ≥ 0.050 µmol/L, and 315 for PEth ≥ 0.30 µmol/L. EtG and PEth concentrations seemed largely independent as the coefficient of determination (r2) between PEth and EtG concentrations was 0.15. However, when the EtG concentrations were evaluated for different subgroups depending on ethanol or PEth concentrations a statistically significant difference between successive higher concentrations was observed. EtG and PEth are independent measures of recent alcohol drinking reflecting different time windows. Their combined measurement in the same blood sample is possible and will provide valuable information regarding recent alcohol consumption as a complement to self-reporting.

Background: Heavy alcohol use, including binge drinking, is associated with high morbidity and mortality among men who have sex with men (MSM). Self‐reported alcohol measures may lead to inaccurate estimates due to recall and social desirability biases. Objective alcohol biomarkers like phosphatidylethanol (PEth) can be used to corroborate self‐report and could help to inform treatment approaches and research strategies for alcohol using MSM. Methods: From 2015 to 2020, alcohol using MSM ≥18 years were enrolled in a randomized controlled trial evaluating the efficacy of naltrexone in reducing binge drinking. Using this trial's baseline data, we applied multivariable logistic regression to identify the correlates of high PEth levels (i.e., ≥87 ng/ml) and concordance between PEth levels and self‐reported heavy drinking. Results: Of 118 MSM, 64% had PEth levels ≥87 ng/ml and 72% had PEth levels that were concordant with self‐reported heavy alcohol use. Factors significantly associated in separate models with elevated PEth levels were income ≥$60,000 (adjusted odds ratio [aOR] = 4.09; 95% CI = 1.13 to 14.82), being employed (aOR = 4.04; 95% CI = 1.45 to 11.32), episodic cannabis use (aOR = 4.63; 95% CI = 1.27 to 16.92), and any alcohol/substance use prior to or during anal intercourse (aOR = 2.52; 95% CI = 1.08 to 5.90). Living with HIV was associated with significantly lower odds of elevated PEth levels (aOR = 0.23; 95% CI = 0.09 to 0.61). Factors associated with significantly higher concordance between PEth levels and self‐reported heavy alcohol use included at least weekly use of poppers (aOR = 6.41; 95% CI = 1.27 to 32.28) and polysubstance use (aOR = 2.53; 95% CI = 1.02 to 6.27). Living with HIV was associated with lower odds of concordance (aOR = 0.36; 95% CI = 0.14 to 0.97). Conclusions: PEth may enhance the detection of heavy drinking among MSM, including the identification of subpopulations that may benefit from targeted alcohol reduction interventions. However, PEth values for MSM living with HIV showed modest concordance with self‐reported alcohol use and may need to be supplemented with additional biomarkers or evaluated against a different cutoff. [ABSTRACT FROM AUTHOR]

Background and aims: Phosphatidylethanol 16:0/18:1 (PEth) is a biomarker for alcohol intake. It has a half‐life of 7.9 days. Chronic alcohol consumption causes high PEth values. It can take weeks before PEth values fall below the decision limit for 'alcohol abstinence'. Our aim was to validate whether alcohol abstinence can be determined based on two consecutive PEth results above the decision limit. Design Observational study. Setting: Belgium, February 2019. The study was linked to a social initiative in Belgium, 'Tournée Minérale'. Participants: Adults (aged > 18 years, n = 796) with varying drinking habits who self‐reportedly refrained from alcohol consumption during the study. Measurements A validated liquid chromatography–tandem mass spectrometry method was used to quantify PEth in participants' dried blood samples, collected at three time‐points via remote fingerprick‐based self‐sampling. Findings A population‐based algorithm to evaluate abstinence based on 95% prediction limits was developed by fitting a linear mixed‐effect model to discern patterns in PEth elimination over time. It took intra‐ and inter‐individual variability into consideration. The algorithm was included in a two‐step decision tree, assessing whether (i) PEth values fell within the prediction interval and (ii) the slope between two PEth values was consistent with no alcohol consumption. Data for 74 participants reporting no alcohol intake during the study were used for validation. With a detection limit of 'four units spread over 14 days', the sensitivity and specificity of the decision tree was 89%. Conclusions: Claims of alcohol abstinence can be verified using a two‐step decision tree for phosphatidylethanol 16:0/18:1 values, even when those values are above the limit for 'alcohol abstinence'. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol overconsumption remains one of the adverse effects associated with bariatric surgery. Many previous studies have used subjective methods to evaluate the prevalence of alcohol overconsumption. In 2018, Örebro University Hospital started to use phosphatidylethanol 16:0/18:1 (PEth) as a screening tool pre- and postbariatric surgery. Research exploring alcohol use after bariatric surgery assessed with PEth is scarce. Aim: The aim of this study is to evaluate the prevalence of alcohol overconsumption in bariatric surgery patients measured 2 years postoperatively with PEth and to identify possible risk factors associated with alcohol overconsumption. Methods: This was a register-based retrospective, observational cohort study with PEth results collected from medical records at Örebro University Hospital. Patients who underwent bariatric surgery between January 2016 and June 2019 and who were registered in the Scandinavian Obesity Surgery Registry (SOReg) were included. Results: PEth results from 410 bariatric surgery patients were identified. PEth values significantly increased from baseline to the postoperative follow-up (from 3.0% before surgery to 8.3% at the 2-year follow-up). In a univariate logistic regression analysis, the associated risk factors were found to be male sex (odds ratio, OR 2.14), older age (OR 1.06), and hypertension (OR 3.32). Conclusion: The prevalence of alcohol overconsumption measured with PEth 2 years after bariatric surgery was 8.3% and was associated with male sex, older age, and hypertension. More studies are needed to validate the results of this study because it is not known whether PEth values are affected by bariatric surgery. [ABSTRACT FROM AUTHOR]

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Under-reporting of alcohol use by HIV-infected patients could adversely impact clinical care. This study examined factors associated with under-reporting of alcohol consumption by patients who denied alcohol use in clinical and research settings using an alcohol biomarker. We enrolled ART-naïve, HIV-infected adults at Mbarara Hospital HIV clinic in Uganda. We conducted baseline interviews on alcohol use, demographics, Spirituality and Religiosity Index (SRI), health and functional status; and tested for breath alcohol content and collected blood for phosphatidylethanol (PEth), a sensitive and specific biomarker of alcohol use. We determined PEth status among participants who denied alcohol consumption to clinic counselors (Group 1, n = 104), and those who denied alcohol use on their research interview (Group 2, n = 198). A positive PEth was defined as ≥8 ng/ml. Multiple logistic regression models were used to examine whether testing PEth-positive varied by demographics, literacy, spirituality, socially desirable reporting and physical health status. Results showed that, among the 104 participants in Group 1, 28.8% were PEth-positive. The odds of being PEth-positive were higher for those reporting prior unhealthy drinking (adjusted odds ratio (AOR): 4.7, 95% confidence interval (CI): 1.8, 12.5). No other factors were statistically significant. Among the 198 participants in Group 2, 13.1% were PEth-positive. The odds of being PEth-positive were higher for those reporting past unhealthy drinking (AOR: 4.6, 95% CI: 1.8, 12.2), the Catholics (AOR: 3.8, 95% CI: 1.3, 11.0) compared to Protestants and lower for the literate participants (AOR: 0.3, 95% CI: 0.1, 0.8). We concluded that under-reporting of alcohol use to HIV clinic staff was substantial, but it was lower in a research setting that conducted testing for breath alcohol and PEth. A report of past unhealthy drinking may highlight current alcohol use among deniers. Strategies to improve alcohol self-report are needed within HIV care settings in Uganda.

Abstract Background Alcohol consumption during pregnancy is associated with major birth defects and developmental disabilities. Questionnaires concerning alcohol consumption during pregnancy underestimate alcohol use while the use of a reliable and objective biomarker for alcohol consumption enables more accurate screening. Phosphatidylethanol can detect low levels of alcohol consumption in the previous two weeks. In this study we aimed to biochemically assess the prevalence of alcohol consumption during early pregnancy using phosphatidylethanol in blood and compare this with self-reported alcohol consumption. Methods To evaluate biochemically assessed prevalence of alcohol consumption during early pregnancy using phosphatidylethanol levels, we conducted a prospective, cross-sectional, single center study in the largest tertiary hospital of the Netherlands. All adult pregnant women who were under the care of the obstetric department of the Erasmus MC and who underwent routine blood testing at a gestational age of less than 15 weeks were eligible. No specified informed consent was needed. Results The study was conducted between September 2016 and October 2017. In total, we received 1,002 residual samples of 992 women. After applying in- and exclusion criteria we analyzed 684 samples. Mean gestational age of all included women was 10.3 weeks (SD 1.9). Of these women, 36 (5.3 %) tested positive for phosphatidylethanol, indicating alcohol consumption in the previous two weeks. Of women with a positive phosphatidylethanol test, 89 % (n = 32) did not express alcohol consumption to their obstetric care provider. Conclusions One in nineteen women consumed alcohol during early pregnancy with a high percentage not reporting this use to their obstetric care provider. Questioning alcohol consumption by an obstetric care provider did not successfully identify (hazardous) alcohol consumption. Routine screening with phosphatidylethanol in maternal blood can be of added value to identify women who consume alcohol during pregnancy.