Phosphatidylethanol in steatotic liver disease

Abstract

Steatotic liver disease (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), and their combination (MetALD). Distinguishing these subclasses relies on accurately assessing current alcohol intake, particularly as subclass-specific drug therapies become available. Traditionally, clinicians have relied on self-reported alcohol intake, but stigma and recall bias can lead to underestimation. Objective biomarkers complementing self-reporting are therefore essential. Phosphatidylethanol (PEth), a blood-based biomarker formed exclusively in the presence of ethanol, has emerged as highly specific for recent alcohol intake, offering a detection window of up to 4 weeks. However, accurate interpretation of PEth measurements requires awareness of various factors influencing blood alcohol concentration and PEth metabolism including drinking pattern, measurement in whole blood vs. dried blood spots and patient characteristics. To improve SLD subclassification, we recommend triangulating the alcohol intake assessment by combining PEth measurements with self-reported alcohol intake and the AUDIT-C questionnaire. This approach can capture underestimation, provides more granular insight into alcohol use, and addresses discrepancies between patient-report and objective alcohol measurements. This review critically evaluates the biochemical basis, pharmacokinetics, ethical implications, and the clinical use of PEth. We highlight its potential to improve both patient care and research in hepatology. Finally, we discuss current unmet needs and future developments that could ultimately support the broader, evidence-based integration of PEth into clinical medicine.

Keywords: AUDIT-C; Alcohol assessment; Alcohol biomarker; Alcohol-related liver disease (ALD); Biomarker validation; Clinical hepatology; Metabolic and alcohol-related liver disease (MetALD); Metabolic dysfunction-associated steatotic liver disease (MASLD); Phosphatidylethanol (PEth); Steatotic liver disease (SLD).