RSS-Feed abonnieren
DOI: 10.1055/a-2340-1201
PEth: internationale Grenzwerte, neue Ansätze und deren Relevanz in der Praxis
PEth: International Cutoff Concentrations, New Approaches, and their Practical Relevance![](https://www.thieme-connect.de/media/suchttherapie/202403/lookinside/thumbnails/2024-02-0016_10-1055-a-2340-1201-1.jpg)
Zusammenfassung
Der Nachweis und die Klassifizierung des Alkoholkonsums spielen eine entscheidende Rolle in verschiedenen gesellschaftlichen Bereichen, sei es im Straßenverkehr, im Gesundheitswesen oder am Arbeitsplatz. Die Verwendung von Alkoholbiomarkern ermöglicht eine objektive Beurteilung der Trinkgewohnheiten sowohl im klinischen als auch im forensischen Bereich. Neben etablierten Biomarkern wie Ethylglukuronid (EtG) oder Carbohydrat-defizientes Transferrin (CDT) gewinnt Phosphatidylethanol (PEth) als direkter Alkoholbiomarker zunehmend an Bedeutung. PEth wird nur gebildet, wenn Alkohol im Körper vorhanden ist und liefert als Bestandteil der zellulären Fraktion des Blutes Informationen über das Konsumverhalten. Für die Interpretation wird derzeit hauptsächlich das in menschlichem Blut am stärksten vertretene PEth 16:0/18:1 verwendet und üblicherweise auf Basis von zwei Grenzwerten interpretiert. Diese Grenzwerte erlauben eine Einteilung in: 1.) Abstinenz/minimalen Alkoholkonsum, 2.) Alkoholkonsum und 3.) exzessiven, chronischen Alkoholkonsum. In diesem Artikel werden die derzeitigen Grenzwerte für die Interpretation von PEth-Konzentrationen diskutiert und weitere Bemühungen zur Überprüfung und Gewährleistung der Vergleichbarkeit zwischen verschiedenen Laboren vorgestellt. Darüber hinaus werden aktuelle und neue Ansätze im Bereich der PEth-Forschung präsentiert. Dazu gehören neue Entwicklungen für die Normalisierung des Hämatokrits bei der Messung von PEth, die Verwendung von Point-of-care-testing (POCT) Geräten zur Messung von PEth am Ort der Blutentnahme, der Nachweis von PEth in Speichel und Wangenabstrichen, die Verwendung von Immunoassays, sowie das Potential des neu entdeckten Biomarkers Lyso-PEth. Es bleibt abzuwarten, wie sich diese neuen Ansätze entwickeln und möglicherweise die Überwachung des Alkoholkonsums und die Diagnose von Alkoholkonsumstörungen in Zukunft verändern oder verbessern können. Grundsätzlich besteht noch großes Potenzial für Fortschritte in Richtung höherer Sensitivität, Spezifität und der Anwendbarkeit in verschiedenen klinischen Kontexten.
Abstract
The detection of alcohol consumption and its classification plays a crucial role in various societal domains, whether in road traffic, healthcare, or the workplace. The use of alcohol biomarkers allows for an objective assessment of drinking habits in both clinical and forensic settings. In addition to established markers such as ethylglucuronide (EtG) or carbohydrate-deficient transferrin (CDT), phosphatidylethanol (PEth) is gaining increasing significance as an alcohol biomarker. PEth is only formed when alcohol is present in the body. As a component of the cellular fraction of the blood, PEth provides information on consumption behavior in relation with alcohol. PEth 16:0/18:1, the predominant species in human blood, is currently used for the interpretation of consumption behaviors based on two cut-off concentrations. These cut-offs allow the categorization into: 1.) abstinence/minimal alcohol consumption, 2.) alcohol consumption, and 3.) excessive, chronic alcohol consumption. This article discusses the currently used cut-off concentrations for the interpretation of PEth levels and presents ongoing efforts to verify and ensure comparability between different laboratories. Furthermore, current and new approaches in PEth research are addressed. These include new developments for normalizing hematocrit in PEth measurements, the use of point-of-care-testing (POCT) devices for on-site measurement of PEth, the detection of PEth concentrations in saliva and buccal swab, the use of immunoassays, and the potential of the newly discovered potential biomarker lyso-PEth. It remains to be seen how these new approaches will evolve and potentially change or enhance the monitoring of alcohol consumption and the diagnosis of alcohol use disorders in the future. In essence, there is still great potential for progress towards higher sensitivity, specificity, and applicability in various clinical contexts.
Publikationsverlauf
Artikel online veröffentlicht:
12. August 2024
© 2024. Thieme. All rights reserved.
Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart,
Germany
-
Literatur
- 1 Gnann H, Engelmann C, Skopp G. et al. Identification of 48 homologues of phosphatidylethanol in blood by LC-ESI-MS/MS. Anal Bioanal Chem 2010; 396: 2415-2423 DOI: 10.1007/s00216-010-3458-5.
- 2 Neumann J, Böttcher M. Zur Präanalytik der PEth Bestimmung. Zeitschrift für Verkehrssicherheit 2022; 68: 377-382
- 3 Beck O, Mellring M, Löwbeer C. et al. Measurement of the alcohol biomarker phosphatidylethanol (PEth) in dried blood spots and venous blood – importance of inhibition of post-sampling formation from ethanol. Analytical and Bioanalytical Chemistry 2021; 413: 5601-5606 DOI: 10.1007/s00216-021-03211-z.
- 4 Helander A, Böttcher M, Dahmen N, Beck O. Elimination Characteristics of the Alcohol Biomarker Phosphatidylethanol (PEth) in Blood during Alcohol Detoxification. Alcohol and Alcoholism 2019; 54: 251-257 DOI: 10.1093/alcalc/agz027.
- 5 Luginbühl M, Weinmann W, Butzke I, Pfeifer P. Monitoring of direct alcohol markers in alcohol use disorder patients during withdrawal treatment and successive rehabilitation. Drug Test Anal 2019; 11: 859-869 DOI: 10.1002/dta.2567.
- 6 Stöth F, Weinmann W, Soravia LM, Pfeifer P. Evaluation of Phosphatidylethanol Elimination in Alcohol Use Disorder Patients Undergoing Withdrawal Treatment. Alcohol Alcohol 2023; 58: 266-273 DOI: 10.1093/alcalc/agad010.
- 7 Van Uytfanghe K, Heughebaert L, Abatih E, Stove CP. Set-up of a population-based model to verify alcohol abstinence via monitoring of the direct alcohol marker phosphatidylethanol 16:0/18:1. Addiction 2022; 117: 2108-2118 DOI: 10.1111/add.15811.
- 8 Novak L, Soravia LM, Bünter A. et al. Alcohol Biomarker Phosphatidylethanol as a Predictor of the Severity of Alcohol Withdrawal Syndrome. Alcohol Alcohol 2023; 58: 198-202 DOI: 10.1093/alcalc/agac071.
- 9 Luginbühl M, Bekaert B, Suesse S, Weinmann W. Detox shampoos for EtG and FAEE in hair – Results from in vitro experiments. Drug Test Anal 2019; 11: 870-877 DOI: 10.1002/dta.2570.
- 10 Luginbühl M, Nussbaumer S, Weinmann W. Decrease of ethyl glucuronide concentrations in hair after exposure to chlorinated swimming pool water. Drug Test Anal 2018; 10: 689-693 DOI: 10.1002/dta.2295.
- 11 Aboutara N, Jungen H, Szewczyk A. et al. PEth 16:0/18:1 and 16:0/18:2 after consumption of low doses of alcohol – A contribution to cutoff discussion. Drug Testing and Analysis 2023; 15: 104-114 DOI: 10.1002/dta.3376.
- 12 Hill-Kapturczak N, Dougherty DM, Roache JD. et al. Differences in the Synthesis and Elimination of Phosphatidylethanol 16:0/18:1 and 16:0/18:2 After Acute Doses of Alcohol. Alcoholism: Clinical and Experimental Research 2018; 42: 851-860 DOI: 10.1111/acer.13620.
- 13 Stöth F, Koch K, Bantle M. et al. Increase of PEth after Single Consumption of Alcohol and Evaluation of a Volumetric DBS Filter Paper Device. J Anal Toxicol 2023; 47: 379-384 DOI: 10.1093/jat/bkad009.
- 14 Simon TW. Providing context for phosphatidylethanol as a biomarker of alcohol consumption with a pharmacokinetic model. Regulatory Toxicology and Pharmacology 2018; 94: 163-171 DOI: 10.1016/j.yrtph.2018.01.029.
- 15 Piano MR, Tiwari S, Nevoral L, Phillips SA. Phosphatidylethanol Levels Are Elevated and Correlate Strongly with AUDIT Scores in Young Adult Binge Drinkers. Alcohol and Alcoholism 2015; 50: 519-525 DOI: 10.1093/alcalc/agv049.
- 16 Walther L, de Bejczy A, Löf E. et al. Phosphatidylethanol is Superior to Carbohydrate-Deficient Transferrin and γ-Glutamyltransferase as an Alcohol Marker and is a Reliable Estimate of Alcohol Consumption Level. Alcoholism: Clinical and Experimental Research 2015; 39: 2200-2208 DOI: 10.1111/acer.12883.
- 17 WHO. Alcohol, heavy episodic drinking (drinkers only) past 30 days. In: Indicator Metadata Registry List.
- 18 Helander A, Hansson T. National harmonization of the alcohol biomarker PEth. Lakartidningen 2013; 110: 1747-1748
- 19 Helander A, Hansson T. The alcohol biomarker phosphatidylethanol (PEth) – test performance and experiences from routine analysis and external quality assessment. Scandinavian Journal of Clinical and Laboratory Investigation 2023; 83: 424-431 DOI: 10.1080/00365513.2023.2253734.
- 20 Ulwelling W, Smith K. The PEth Blood Test in the Security Environment: What it is; Why it is Important; and Interpretative Guidelines. Journal of Forensic Sciences 2018; 63: 1634-1640 DOI: 10.1111/1556-4029.13874.
- 21 Luginbühl M, Wurst FM, Stöth F. et al. Consensus for the use of the alcohol biomarker phosphatidylethanol (PEth) for the assessment of abstinence and alcohol consumption in clinical and forensic practice (2022 Consensus of Basel). Drug Test Anal 2022; 14: 1800-1802 DOI: 10.1002/dta.3340.
- 22 DGVP, DGVM. Urteilsbildung in der Fahreignungsbegutachtung – Beurteilungskriterien. 2022
- 23 Luginbühl M, Stöth F, Weinmann W, Gaugler S. Fully automated correction for the hematocrit bias of non-volumetric dried blood spot phosphatidylethanol analysis. Alcohol 2021; 94: 17-23 DOI: 10.1016/j.alcohol.2021.04.002.
- 24 Luginbühl M, Gaugler S. Addressing New Possibilities and New Challenges: Automated Nondestructive Hematocrit Normalization for Dried Blood Spots. Ther Drug Monit 2021; 43: 346-350 DOI: 10.1097/ftd.0000000000000887.
- 25 White D, Abbas Zadeh S, O'Halloran S. et al. Hematocrit Correction of Whole Blood Phosphatidylethanol Concentrations to Estimate Erythrocyte PEth Concentrations: Sensitivity, Specificity and Influence on Test Utility. J Anal Toxicol 2023; 47: 305-310 DOI: 10.1093/jat/bkac084.
- 26 White D, Fitzpatrick M, McWhinney B. et al. LC-MS/MS analysis of erythrocyte phosphatidylethanol in haematocrit-corrected whole blood versus isolated erythrocytes: Results of an inter-laboratory comparison. Drug Test Anal 2024; 16: 251-258 DOI: 10.1002/dta.3537.
- 27 Pandey S, Hu Y, Anderson PL. et al. Miniature mass spectrometer-based point-of-care assay for measuring phosphatidylethanol in blood. Analyst 2023; 148: 1430-1436 DOI: 10.1039/D3AN00098B.
- 28 Helander A, Ullah S, Beck O. Phosphatidylethanols in Breath: A Possible Noninvasive Screening Test for Heavy Alcohol Consumption. Clinical Chemistry 2015; 61: 991-993 DOI: 10.1373/clinchem.2015.239848.
- 29 Ullah S, Helander A, Beck O. Identification and quantitation of phosphatidylethanols in oral fluid by liquid chromatography-tandem mass spectrometry. Clin Chem Lab Med 2017; 55: 1332-1339 DOI: 10.1515/cclm-2016-0752.
- 30 Gaulier JM, Hakim F, Journe B. Phosphatidylethanol measured on a buccal smear. 2024 PEth in Mind Conference. 2024. Lucerne:
- 31 Nissinen AE, Mäkelä SM, Vuoristo JT. et al. Immunological detection of in vitro formed phosphatidylethanol – an alcohol biomarker – with monoclonal antibodies. Alcohol Clin Exp Res 2008; 32: 921-928 DOI: 10.1111/j.1530-0277.2008.00656.x.
- 32 Sonmez MB, Cinar RK, Gorgulu Y. et al. Evaluation of phosphatidylethanol by ELISA for detection of excessive alcohol use compared with traditional biomarkers: a case-control study. Psychiatry and Clinical Psychopharmacology 2017; 27: 41-46 DOI: 10.1080/24750573.2017.1293249.
- 33 Nissinen AE, Laitinen LM, Kakko S. et al. Low plasma antibodies specific for phosphatidylethanol in alcohol abusers and patients with alcoholic pancreatitis. Addict Biol 2012; 17: 1057-1067 DOI: 10.1111/j.1369-1600.2010.00279.x.
- 34 Johnson LJ, Chan FV, Muyindike WR. et al. PEth immunoassay: a semi-quantitative ELISA for assessment of alcohol consumption. In: Research Society on Alcohol. Bellevue, Washington: Echelon Biosciences; 2023
- 35 Bantle M, van Tieghem L, Weinmann W, Luginbühl M. Lyso-phosphatidylethanol detected by LC-MS/MS as a potential new marker for alcohol consumption. European Journal of Mass Spectrometry 2023; 29: 338-347 DOI: 10.1177/14690667231200143.
- 36 Munder PG, Modolell M, Andreesen R. et al. Lysophosphatidylcholine (Lysolecithin) and its Synthetic Analogues. Immunomodulating and Other Biologic Effects. In: Chedid L, Miescher PA, Mueller-Eberhard HJ, Hrsg. Immunostimulation. Berlin, Heidelberg: Springer Berlin Heidelberg; 1980: 177-193 DOI: 10.1007/978-3-642-67809-7_12