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.