Prospective study of phosphatidylethanol (PEth) as a diagnostic biomarker for identifying alcohol use disorder (AUD) among participants at risk for steatotic liver disease

Background Although alcohol use disorder (AUD) is common in steatotic liver disease (SLD), its true prevalence is unknown because Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis (gold-standard) is rarely used in liver clinics, highlighting the need for objective biomarkers. Objective To determine AUD prevalence in SLD and assess performance of phosphatidylethanol (PEth) as an objective AUD biomarker. Design This prospective cohort study included well-phenotyped adults at risk of SLD (Southern California, USA). Participants underwent a standardised research visit including the Alcohol Use Disorders Identification Test and Skinner questionnaire, PEth, MRI-proton density fat fraction (PDFF) and MRI elastography. Participants were classified into SLD subcategories (2023 SLD criteria); AUD diagnosis by DSM-5 criteria. We examined the diagnostic test performance of PEth for AUD diagnosis (area under the receiver operating characteristic curve (AUROC)). Results We included 848 participants with a median age of 52 (42–61) years. A total of 605 (71.3%) had SLD (84.8% metabolic dysfunction-associated steatotic liver disease (MASLD), 9.8% metabolic dysfunction and alcohol-related liver disease (MetALD), 5.4% alcohol-related liver disease (ALD)). The prevalence of AUD in SLD was 6.6%. AUD prevalence by SLD subtype was 1.6% in MASLD, 30.5% in MetALD and 42.4% in ALD. PEth had acceptable diagnostic accuracy for AUD (AUROC 0.78, 95% CI 0.71 to 0.85, p<0.01), with a specificity of 91% for ≥43 ng/mL. PEth outperformed aspartate aminotransferase:alanine aminotransferase ratio, gamma-glutamyltransferase and mean corpuscular volume (p<0.05 for all comparisons), without differences with Alcohol Use Disorders Identification Test-Consumption. We validated our findings in an independent cohort with cirrhosis. Conclusion Using a well-characterised cohort that included MRI-PDFF paired with PEth and DSM-5 criteria, we demonstrate that PEth may be used as an objective biomarker of AUD in SLD.