Evaluation of Phosphatidylethanol Elimination in Alcohol Use Disorder Patients Undergoing Withdrawal Treatment

Abstract

Aims Phosphatidylethanol (PEth) is used to monitor alcohol consumption in alcohol use disorder (AUD). In this study, we aim to evaluate the elimination time of PEth with regard to the clinically established 200 and 20 ng/ml cutoffs for PEth 16:0/18:1. Methods Data from 49 patients undergoing treatment for AUD were evaluated. PEth concentrations were measured at the beginning and repeatedly during the treatment period of up to 12 weeks to monitor the elimination of PEth. We evaluated the time in weeks until the cutoff concentrations of <200 and <20 ng/ml were achieved. The correlation between the initial PEth concentration and the number of days until the PEth concentration had dropped below 200 and 20 ng/ml was assessed by calculating Pearson’s correlation coefficients. Results The initial PEth concentrations ranged from <20 to >2500 ng/ml. In 31 patients, the time until the cutoff values were reached could be documented. Even after 6 weeks of abstinence, PEth concentrations above the cutoff of 200 ng/ml could still be detected in two patients. A strong significant positive correlation was found between the initial PEth concentration and the time required to drop below the two cutoffs. Conclusion A waiting period of more than 6 weeks after declared abstinence should be granted for individuals with AUD before using only one single PEth concentration to assess the consumption behavior. However, we recommend to always use at least two PEth concentrations for the evaluation of alcohol-drinking behaviors in AUD patients.

Brief history of the alcohol biomarkers CDT, EtG, EtS, 5‐HTOL, and PEth

“…137 The elimination half-life of 16:0/18:1 from blood shows large interindividual variation, and in heavy drinkers during abstinence, this was estimated to be between 4 and 10 days (median 6 days). [138][139][140] Accordingly, PEth might be detected in blood for up to 20-40 days after termination of a drinking binge, although a lot depends on intensity and duration of previous ethanol ingestion. 132,141 Today's analytical methods for PEth have become so sensitive that some homologs can be detected in blood after a single exposure to ethanol.…”

“But I didn’t drink!”: What to do with discordant phosphatidylethanol results

“…PEth has been validated in chronic liver disease and a detection threshold of 20 ng/mL is 96% specific (73% sensitive) for any drinking in the last 30 days and 97% sensitive (66% specific) for the detection of four drinks per day 17 . While multiple lab values are ideal to adequately characterize patients’ alcohol use patterns, 14 LT teams use PEth inconsistently 18 . PEth’s quantitative value correlates with scores on the Alcohol Use Disorder Identification Test 19,20 and different levels of alcohol use: <20 ng/mL, little or no drinking; 20–200 ng/mL, moderate consumption; and >200 ng/mL, heavy consumption 16,17 .…”

“…It can be analyzed from whole blood or dried blood spots, though some discrepancies between these methods have been identified 11,12 . PEth is a lipid species; 16:0/18:1 and 16:0/18:2 are the most common subtypes in humans, 13 formed by phospholipase D when ethanol is present in the bloodstream, which may remain positive for up to 6 weeks in some patients; 14 levels may be sex-dependent 15 . It monitors abstinence well 12 and no false positives exist when testing patients for any alcohol consumption 16 .…”

Lyso-phosphatidylethanol detected by LC-MS/MS as a potential new marker for alcohol consumption

“…7 Nowadays, PEth is routinely analysed by LC-ESI-MS/MS in laboratories in Europe and US, for monitoring drinking behaviour and abstinence, e.g., for driving aptitude assessments (DAA) or abstinence monitoring in the clinical field. [12][13][14] However, one single PEth-value is only a snapshot at the time of the sample collection and does not necessarily provide further insight into patients drinking behaviour over a long time. When the drinking behaviour has been changed recently, e.g., from excessive drinking to abstinence or low drinking amounts, it may take several weeks until steady-state PEth concentrations are reached, due to PEth's prolonged terminal half-life of up to 13 days.…”

“…15 In case of long term excessive alcohol consumption, PEth 16:0/18:1 concentrations > 200 ng/mL may be detected although a 4 week abstinence period was maintained. 13 To avoid potentially wrong assignments when consumption habits have changed recently, multiple samples should be taken in bi-weekly to monthly intervals. An alternative could be the additional analysis of markers which are structurally related to PEth, since they might have different elimination profiles.…”