Phosphatidylethanol as an outcome measure in treatment aimed at controlled drinking.

BACKGROUND: Phosphatidylethanol (PEth) is a specific marker of alcohol intake, used both as a screening method for hazardous use and as an outcome measure in the treatment of alcohol use disorder (AUD). However, what cut-off values to apply for hazardous use in a treatment setting is still unclear. We aimed to investigate the correlation between PEth and self-reported drinking and identify the optimal cut-off for hazardous use, for patients with AUD and a stated goal of controlled drinking. METHODS: We used data from a randomized controlled trial of two different psychological treatments aiming for controlled drinking, conducted within specialized addiction care in Stockholm, Sweden. A total of 181 patients left samples that could be included in the current analysis. Outcomes were measured at five different time points over 2 years of follow-up. PEth 16:0/18:1 values were correlated with subjective reports of recent drinking based on the Timeline Follow-Back Method. RESULTS: The correlation between PEth and self-reported alcohol intake increased significantly over time, with the weakest correlation found at baseline (Spearman's ρ = 0.42) and the strongest at the 104-week follow-up (ρ = 0.69). When used to indicate hazardous drinking according to Swedish guidelines (≥10 units per week), receiver operating characteristic analysis revealed PEth ≥ 0.22 µmol/l to be the optimal cut-off. CONCLUSIONS: PEth is a useful outcome measure that can be used to validate subjective reports of current drinking. In a treatment setting aimed at controlled drinking, the accuracy of patients' self-report measures seems to improve over time. In this context, a PEth value of ≥0.22 µmol/l is a sensitive and specific indicator of hazardous drinking.

Utilising paired measurements of phosphatidylethanol to monitor early success in alcohol abstinence.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION AND CONCLUSIONS: 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.

Interlaboratory comparison of phosphatidylethanol in dried blood spots using different sampling devices.

Phosphatidylethanol (PEth) has become an important marker to assess drinking behaviour and monitor abstinence. Despite its increasing use, knowledge on robustness and standardization and comparability of methods and results are still limited. In 2022, the first international consensus for the use of PEth and its interpretation was published. To establish an experience-based foundation for further harmonization, three rounds of interlaboratory comparison using microsamples were conducted. Participating laboratories sent their sampling devices to the laboratory of Forensic Toxicology at the University of Bern, where for each round, four different authentic blood samples were applied to the devices and sent back. The PEth 16:0/18:1 target concentrations covered a range between 16 and 474 ng/mL (0.023 and 0.676 µmol/L, respectively) and included sample concentrations close to the decision limits of 20 and 200 ng/mL (0.025 and 0.28 µmol/L, respectively). Evaluation of the results based on guidelines by Horwitz and the Society of Toxicological and Forensic Chemistry (GTFCh) showed that 73% of all participating laboratories quantified and reported all samples (N = 4 for each round) within the acceptable limits. More than 90% quantified and reported at least one sample within the acceptable limits.

Evaluation and comparison of sensitivity of alcohol biomarkers PEth, EtG and EtPa in civil cases in England 2022-2023.

This study details trends in direct alcohol biomarker concentrations from civil cases within the United Kingdom (UK). Our subject cohort in this study related to family law litigation, where an individual was subject to an alcohol monitoring order by the court. This monitoring was conducted by quantification of alcohol biomarkers Phosphatidlyethanol (PEth) in dried blood spots (DBS) and Ethyl Glucuronide (EtG) and Ethyl Palmitate (EtPa) from hair segments. In total 298 PEth cases predominantly from the South East of England during the period July 2022 to August 2023 were analysed for alcohol biomarkers in DBS and hair. Subjects alcohol intake was classified as abstinence/low alcohol consumption, moderate or excessive alcohol consumption, based on a combination of Society for Hair Testing and PEth Net guidelines. Our results indicate that 33 % of PEth concentrations were consistent with excessive alcohol use (>200 ng/mL DBS), with 36 % consistent with social or moderate alcohol use (20-200 ng/mL DBS). In relation to EtG and EtPa 23 % and 31 % of subjects were classified as excessive alcohol users respectively. This study indicates that DBS sampling of PEth is a more sensitive predictor of alcohol use, in particular, at differentiating between moderate and excessive alcohol use compared to EtG and EtPa testing in hair. The authors suggest that increased frequency in the sampling of PEth in DBS (multiple occasions per month) may provide a more accurate assessment and simplification of the interpretation criteria of alcohol patterns rather than the combined hair testing and DBS sampling that are typically requested by UK courts.

AUDIT C compared to PEth in middle-aged volunteers.

AIMS: To compare Alcohol Use Disorders Identification Test (AUDIT C) to phosphatidylethanol (PEth) in middle-aged randomly selected volunteers. Apply previously suggested lower cut-offs for PEth using moderate alcohol intake according to AUDIT C as a reference. METHODS: Within the Swedish CardioPulmonary BioImage Study, 2255 middle-aged (50-64 years of age) volunteers in northern Sweden participated in comparing AUDIT C to PEth 16:0/18:1. RESULTS: There was a moderate correlation between PEth 16:0/18:1 and AUDIT C (r = 0.66). None of the participants with the AUDIT C-score 0 had a measurable PEth. Of moderate alcohol consumers, according to AUDIT C (AUDIT C 1-3 women, 1-4 men), 96% had a PEth below 0.3 µmol/L, 91% had a PEth below 0.16 µmol/L, and 84% had a PEth below 0.11 µmol/L. With PEth equivalent to excessive alcohol consumption (≥0.3 µmol/L), 26% had an AUDIT C-score below excessive alcohol consumption (<4 for women and <5 for men). Thirty percent of patients with a PEth ≥0.16 µmol/L had an AUDIT C-score below excessive alcohol consumption, and 37% had a PEth ≥0.11 µmol/L. We found no significant correlation between BMI and PEth or AUDIT C. CONCLUSIONS: There is a significant correlation between AUDIT C and PEth. Using AUDIT C alone, 26% of high-consumers, according to PEth, are not found in our cohort, but an AUDIT C-score of 0 will exclude high consumption, according to PEth. Our findings support the current cut-off for PEth of 0.3 µmol/L, but a lower cut-off seems reasonable.

The effect of incidental ethanol exposures on the formation of blood phosphatidylethanol.

Blood phosphatidylethanol (PEth), a metabolite of ethanol, is emerging as a direct biomarker of choice for characterizing ethanol consumption in clinical, research, and forensic contexts. An accumulating body of evidence, and a recent international consensus conference, supports a cutoff of 20 µg/L of PEth (16:0/18:1) to distinguish abstinence from beverage ethanol consumption. There is a dearth of research, however, on whether exposures to nonbeverage ethanol sources are sufficient to produce PEth concentrations that exceed this cutoff. To explore this possibility, we recruited 30 participants, who indicated past-90-day abstinence from beverage alcohol, to characterize their past-30-day nonbeverage ethanol exposures (including source, frequency, and intensity of exposures) and to undergo PEth testing. Two of the 30 participants (6.7%) produced PEth concentrations ≥20 µg/L. One of these participants (PEth = 26 µg/L) reported multiple ethanol exposure sources, including near-daily intensive exposures to ethanol vapor. The other participant (PEth = 49 µg/L) reported only once-daily use of an ethanol-containing mouthwash; the veracity of his abstinence claim is refuted. The results of this study support a rebuttable presumption that PEth ≥20 µg/L is indicative of beverage ethanol consumption. They suggest, however, that intensive, incidental alcohol exposures have the potential, under unusual circumstances, to result in PEth concentrations that modestly exceed this threshold.

Identification of Alcohol Use Prior to Major Cancer Surgery: Timeline Follow Back Interview Compared to Four Other Markers.

BACKGROUND: The postoperative complication rate is 30-64% among patients undergoing muscle-invasive and recurrent high-risk non-muscle-invasive bladder cancer surgery. Preoperative risky alcohol use increases the risk. The aim was to evaluate the accuracy of markers for identifying preoperative risky alcohol. METHODS: Diagnostic test sub-study of a randomized controlled trial (STOP-OP trial), based on a cohort of 94 patients scheduled for major bladder cancer surgery. Identification of risky alcohol use using Timeline Follow Back interviews (TLFB) were compared to the AUDIT-C questionnaire and three biomarkers: carbohydrate-deficient transferrin in plasma (P-CDT), phosphatidyl-ethanol in blood (B-PEth), and ethyl glucuronide in urine (U-EtG). RESULTS: The correlation between TLFB and AUDIT-C was strong (ρ = 0.75), while it was moderate between TLFB and the biomarkers (ρ = 0.55-0.65). Overall, sensitivity ranged from 56 to 82% and specificity from 38 to 100%. B-PEth showed the lowest sensitivity at 56%, but the highest specificity of 100%. All tests had high positive predictive values (79-100%), but low negative predictive values (42-55%). CONCLUSIONS: Despite high positive predictive values, negative predictive values were weak compared to TLFB. For now, TLFB interviews seem preferable for preoperative identification of risky alcohol use.

Relationship between alcohol intake based on daily smartphone-reported consumption and PEth concentrations in healthy volunteers.

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.

Identifying excessive chronic alcohol use with phosphatidylethanol in patients with suspected severe injury-results from the IDART study.

INTRODUCTION: Acute and chronic alcohol use are well-known risk factors for accidents and injuries, and concurrent psychoactive drug use can increase injury risk further. Phosphatidylethanol (PEth) 16:0/18:1 is a biomarker used to determine alcohol consumption the previous 3-4 weeks. The aim was to investigate the prevalence of chronic alcohol use in trauma patients, as determined by PEth 16:0/18:1 concentrations, and how excessive chronic alcohol use relate to demographic variables, injury mechanisms and drug use. SETTING: Patients received at Norwegian trauma hospitals from March 2019 to February 2020. The study is part of the Impairing Drugs and Alcohol as Risk factors for Traumatic Injuries study. METHODS: All patients aged ≥ 16 years received with trauma team were included in the study. Data on injury date and mechanism, gender and age was registered. Blood samples were analyzed for 22 psychoactive medicinal and illicit drugs, ethanol and phosphatidylethanol 16:0/18:1. Regression analyses were conducted to assess associations between alcohol use and gender, age, injury mechanism and drug use. RESULTS AND CONCLUSION: Of the 4845 patients included in the study, 10% had PEth 16:0/18:1 concentration ≥ 600 nM (~430 ng/mL), indicative of excessive chronic alcohol use. Being male, between 44-61 years old, involved in violence, and testing positive for medicinal drugs was associated with excessive chronic alcohol use.Excessive chronic alcohol use was common among males, middle-aged, patients with violence as injury mechanism and those with medicinal drug use. These findings emphasize the need to detect and treat excessive chronic alcohol use among trauma patients.

Phosphatidylethanol (B-PEth) and other direct and indirect biomarkers of alcohol consumption.

When identifying, preventing and treating alcohol use disorder, a correct estimation of alcohol intake is essential. An objective marker is preferred as self-reported alcohol intake suffers from bias, and the use of alcohol biomarkers is increasing globally. An easy-to-use blood biomarker to correctly assess alcohol consumption is an invaluable asset in alcohol treatment strategies, as well as in alcohol research studies. The specific, cumulative, biomarker phosphatidylethanol, mirroring the past two weeks of consumption, has shown superiority over traditional biomarkers and is an attractive choice of proxy for alcohol intake.

Feasibility of a telehealth-based contingency management intervention for alcohol use disorders using the phosphatidylethanol (PEth) 16:0/18:1 alcohol biomarker: a pilot randomized trial.

Background: Phosphatidylethanol (PEth) is a blood-based biomarker for alcohol consumption that can be self-collected and has high sensitivity, specificity, and a longer detection window compared to other alcohol biomarkers.Objectives: We evaluated the feasibility and acceptability of a telehealth-based contingency management (CM) intervention for alcohol use disorder (AUD) using the blood-based biomarker PEth to assess alcohol consumption.Methods: Sixteen adults (7 female, 9 male) with AUD were randomized to Control or CM conditions. Control participants received reinforcers regardless of their PEth levels. CM participants received reinforcers for week-to-week decreases in PEth (Phase 1) or maintenance of PEth consistent with abstinence (<20 ng/mL, Phase 2). Blood samples were self-collected using the TASSO-M20 device. Acceptability was assessed by retention in weeks. Satisfaction was assessed with the Client Satisfaction Questionnaire (CSQ-8) and qualitative interviews. The primary efficacy outcome was PEth-defined abstinence. Secondary outcomes included the proportion of visits with PEth-defined heavy alcohol consumption, negative urine ethyl glucuronide results, and self-reported alcohol use.Results: Retention averaged 18.6 ± 8.8 weeks for CM participants. CM participants reported high levels of satisfaction (CSQ-8, Mean = 30.3 ± 1.5). Interview themes included intervention positives, such as staff support, quality of life improvement, and accountability. 72% of PEth samples from CM participants were consistent with abstinence versus 34% for Control participants (OR = 5.0, p = 0.007). PEth-defined heavy alcohol consumption was detected in 28% of CM samples and 52% of Control samples (OR = 0.36, p = 0.159). CM participants averaged 1.9 ± 1.7 drinks/day versus 4.2 ± 6.3 for Control participants (p = 0.304).Conclusion: Results support the acceptability and satisfaction of a telehealth PEth-based CM intervention, though a larger study is needed to assess its efficacy [NCT04038021].

LC-MS/MS analysis of erythrocyte phosphatidylethanol in haematocrit-corrected whole blood versus isolated erythrocytes: Results of an inter-laboratory comparison.

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.

Predictive risk markers in alcoholism.

The medical disorders of alcoholism rank among the leading public health problems worldwide and the need for predictive and prognostic risk markers for assessing alcohol use disorders (AUD) has been widely acknowledged. Early-phase detection of problem drinking and associated tissue toxicity are important prerequisites for timely initiations of appropriate treatments and improving patient's committing to the objective of reducing drinking. Recent advances in clinical chemistry have provided novel approaches for a specific detection of heavy drinking through assays of unique ethanol metabolites, phosphatidylethanol (PEth) or ethyl glucuronide (EtG). Carbohydrate-deficient transferrin (CDT) measurements can be used to indicate severe alcohol problems. Hazardous drinking frequently manifests as heavy episodic drinking or in combinations with other unfavorable lifestyle factors, such as smoking, physical inactivity, poor diet or adiposity, which aggravate the metabolic consequences of alcohol intake in a supra-additive manner. Such interactions are also reflected in multiple disease outcomes and distinct abnormalities in biomarkers of liver function, inflammation and oxidative stress. Use of predictive biomarkers either alone or as part of specifically designed biological algorithms helps to predict both hepatic and extrahepatic morbidity in individuals with such risk factors. Novel approaches for assessing progression of fibrosis, a major determinant of prognosis in AUD, have also been made available. Predictive algorithms based on the combined use of biomarkers and clinical observations may prove to have a major impact on clinical decisions to detect AUD in early pre-symptomatic stages, stratify patients according to their substantially different disease risks and predict individual responses to treatment.

The alcohol biomarker phosphatidylethanol (PEth) - test performance and experiences from routine analysis and external quality assessment.

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.

Artificial elevation of phosphatidylethanol due to red blood cell transfusion.

INTRODUCTION: Phosphatidylethanol (PEth) is a marker of alcohol consumption used in clinical and forensic settings. PEth positivity in individuals expected to abstain from alcohol can have serious consequences. PEth is located on erythrocytes, thus packed red blood cell (pRBC) transfusion is a potential cause of false-positive results. This report is the first to demonstrate this phenomenon in an authentic patient who was negative for PEth immediately prior to transfusion. METHODS: Residual blood samples collected for clinical testing before and after pRBC transfusion and citrated pRBC segments were tested for PEth homologues 16:0/18:1 (POPEth) and 16:0/18:2 (PLPEth) by liquid chromatography - tandem mass spectrometry with limit of quantitation 10 ng/mL (0.01 µmol/L). CASE: A 56-year-old male with new-onset leukemia required transfusion of 4 pRBC units on hospital days 1-2. Blood collected at admission (day 0) showed POPEth and PLPEth < 10 ng/mL (<0.01 µmol/L). Blood collected after completion of the fourth pRBC transfusion demonstrated POPEth = 57 ng/mL (0.08 µmol/L), PLPEth = 38 ng/mL (0.05 µmol/L). One citrated segment demonstrated extremely elevated PEth, supporting pRBC transfusion as the source. DISCUSSION: This case demonstrates pRBC transfusion elevating PEth to concentrations associated with moderate alcohol consumption. Studies suggest that healthy individuals (potential donors) could have PEth concentrations sufficient to cause significant elevation of PEth from a single pRBC unit. This is concerning for populations such as liver transplant candidates who are required to abstain from alcohol, but whose disease sequelae may require pRBC transfusion. CONCLUSIONS: pRBC transfusion can artificially elevate PEth into clinically and forensically relevant ranges. Individuals interpreting toxicology testing should consider recent pRBC transfusion when evaluating PEth concentrations.

Factors associated with a positive phosphatidylethanol test during liver transplantation evaluation.

BACKGROUND: Early identification of alcohol use is crucial for informing recommendations of appropriate follow-up treatment pre-liver transplant and optimizing post-liver transplant outcomes. The purpose of the study was to investigate whether there are psychosocial factors associated with a positive PEth test. METHODS: All patients who underwent a routine pre-surgical psychological evaluation for liver transplant listing (all etiologies, including acute liver failure, dual organ, and re-transplantation) at a single health care system in 2020 were included in a retrospective chart review. Data extraction included results from PEth testing and information from the psychological evaluation (i.e., demographic, psychiatric symptoms, and cognitive functioning). RESULTS: There were 158 patients (73.8%) who had a PEth test, of whom 21.5% had a positive result (n = 34). Younger age was associated with a positive PEth (p < .001). ALD status and type of ALD (hepatitis vs. cirrhosis) were also associated with a positive PEth test. Other demographic characteristics and psychiatric symptoms were not associated with a positive PEth result (p > .05). CONCLUSION: Younger age was the only significant demographic variable associated with a positive PEth test. Given the difficulty of predicting who may be using alcohol, it may be useful to use PEth testing for all patients during the pre-liver transplant evaluation and while patients are listed for liver transplant. Early identification of alcohol use through routine PEth testing will help identify patients who are using alcohol and need further treatment for alcohol use to optimize health and post-transplant outcomes.

Phosphatidylethanol (PEth) in Blood as a Marker of Unhealthy Alcohol Use: A Systematic Review with Novel Molecular Insights.

The Alcohol Use Disorders Identification Test (AUDIT) and its short form, the AUDIT-C, the main clinical instruments used to identify unhealthy drinking behaviors, are influenced by memory bias and under-reporting. In recent years, phosphatidylethanol (PEth) in blood has emerged as a marker of unhealthy alcohol use. This systematic review aims to investigate the molecular characteristics of PEth and summarize the last ten years of published literature and its use compared to structured questionnaires. A systematic search was performed, adhering to PRISMA guidelines, through "MeSH" and "free-text" protocols in the databases PubMed, SCOPUS, and Web of Science. The inclusion criteria were as follows: PEth was used for detecting unhealthy alcohol consumption in the general population and quantified in blood through liquid chromatography coupled to mass spectrometry, with full texts in the English language. Quality assessment was performed using the JBI critical appraisal checklist. Twelve papers were included (0.79% of total retrieved records), comprising nine cross-sectional studies and three cohort studies. All studies stratified alcohol exposure and quantified PEth 16:0/18:1 through liquid chromatography coupled to mass spectrometry (LC-MS) in liquid blood or dried blood spots (DBS) with lower limits of quantitation (LLOQ) ranging from 1.7 ng/mL to 20 ng/mL. A correlation between blood PEth level and the amount of alcohol ingested in the previous two weeks was generally observed. PEth interpretative cut-offs varied greatly among the included records, ranging from 4.2 ng/mL to 250 ng/mL, with sensitivity and specificity in the ranges of 58-100% and 64-100%, respectively. Although the biomarker seems promising, further research elucidating the variability in PEth formation and degradation, as well as the molecular mechanisms behind that variability, are necessary.

Alcohol-induced Cushing syndrome: report of eight cases and review of the literature.

Introduction: Alcohol-induced hypercortisolism (AIH) is underrecognized and may masquerade as neoplastic hypercortisolism [Cushing syndrome (CS)] obscuring its diagnosis. Objective and methods: In order to characterize AIH, we performed a chart review of eight patients (4 males and 4 females; 2014-2022) referred for evaluation and treatment of neoplastic hypercortisolism - six for inferior petrosal sinus sampling, one due to persistent CS after unilateral adrenalectomy, and one for pituitary surgery for Cushing disease (CD). Five underwent dDAVP stimulation testing. Results: All eight patients had clinical features of hypercortisolism and plasma ACTH levels within or above the reference interval confirming hypothalamic-pituitary mediation. All had abnormal low-dose dexamethasone suppression test and increased late-night salivary cortisol. Only one had increased urine cortisol excretion. In contrast to CD, the 5 patients tested had blunted or absent ACTH and cortisol responses to desmopressin. Two had adrenal nodules and one had abnormal pituitary imaging. Most patients underreported their alcohol consumption and one denied alcohol use. Elevated blood phosphatidyl ethanol (PEth) was required in one patient to confirm excessive alcohol use. All patients had elevations of liver function tests (LFTs) with AST>ALT. Conclusion: AIH is an under-appreciated, reversible cause of non-neoplastic hypercortisolism that is indistinguishable from neoplastic CS. Incidental pituitary and adrenal imaging abnormalities as well as under-reporting of alcohol consumption further confound the diagnosis. Measurement of PEth helps to confirm an alcohol use disorder. Elevations of LFTs (AST>ALT) and subnormal ACTH and cortisol responses to dDAVP help to distinguish AIH from neoplastic hypercortisolism.

Wilson Disease: Uncommon but Not to Be Forgotten.

Wilson disease (WD) is an autosomal recessive genetic disorder caused by mutations of ATP7B, a copper transporter, which results in impaired copper clearance. Its clinical manifestations are varied and can result in a mix of hepatic and neuropsychiatric symptoms. We present the case of a 26-year-old female with a past medical history of alcohol use who presented with right upper quadrant abdominal pain with associated vomiting, jaundice, and fatigue. She was found to have signs and symptoms of decompensated cirrhosis and was initially concerned about superimposed alcoholic hepatitis. With low ceruloplasmin and alkaline phosphatase, the suspicion for WD remained, and the patient underwent liver transplantation due to her worsening clinical status. The quantitative hepatic copper content of the explanted liver was elevated, and genetic testing confirmed the diagnosis of WD. Our case highlights the importance of including WD in the differential of a young patient with severe liver disease, and it highlights the utility of the phosphatidyl ethanol (PEth) test as a marker for chronic severe alcohol use. In patients with a significant alcohol use history, the diagnosis of WD should still be considered for those with reasonable clinical suspicion.

Assessing the sensitivity and specificity of phosphatidylethanol (PEth) cutoffs to identify alcohol exposed pregnancies.

In the literature on alcohol use biomarkers, there has been debate as to what a valid and/or utilitarian cut off level should be for various research applications. In this manuscript, we assessed the sensitivity and specificity of multiple cutoff values for phosphatidylethanol (PEth) from bloodspots relative to self-report, the Alcohol Use Disorder Identification Test (AUDIT) scores, and another alcohol use biomarker ethyl glucuronide (EtG) from fingernails in a sample of 222 pregnant women in the Western Cape Province of South Africa. Receiver operating characteristic (ROC) curves were used to assess the area under the curve (AUC) and assess PEth cutoff values of ≥2, ≥4, ≥8, ≥14, and ≥20 nanograms per milliliter (ng/ml). The highest AUC value was attained when PEth was compared to an AUDIT score of 1 or more. Depending on the cutoff used to determine alcohol consumption, PEth identified 47%-70% of the individuals as alcohol-consuming while 62.6%-75.2% were identified by self-reported measures, and 35.6% were identified by EtG. In this sample, sensitivity and accuracy were highest at less stringent PEth cutoffs when compared to self-report, AUDIT score of 1 or more, 5 or more, 8 or more, and EtG ≥ 8 picograms per milligram (pg/mg). For research purposes, less stringent cutoffs, such as PEth ≥ 8 ng/ml, may be considered a valid, positive cutoff for identifying women who consume alcohol during pregnancy in this population. A cutoff of PEth ≥ 20 ng/ml may miss individuals who reported consuming alcohol (false negatives).