Clinical utility of phosphatidylethanol to detect underreported alcohol use and enhance steatotic liver disease subclassification

Abstract

Background & aims: The 2023 subclassification of steatotic liver disease (SLD) relies on self-reported alcohol use, which lacks diagnostic precision in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity. In this study, we aimed to estimate the prevalence of underreported alcohol use, identify its independent predictors, and enhance SLD subclassification using PEth in a large, population-based cohort of individuals with overweight/obesity and SLD from the US.

Methods: This is a cross-sectional analysis of a prospective study including 391 community-dwelling adults with overweight/obesity and SLD, as defined by MRI-derived proton density fat fraction ≥5%, residing in Southern California. Participants underwent a standardized clinical research visit, including MRI assessment and PEth testing.

Results: In this cohort, the mean (SD) age and BMI were 51 (13) years and 33 (6) kg/m², respectively. As PEth levels increased, insulin resistance and hemoglobin A1c decreased, while blood pressure and high-density lipoprotein cholesterol increased. Of individuals with SLD, 15.9% (95% CI 12.2%-19.5%) underreported their alcohol consumption. Male sex, absence of type 2 diabetes, and White race were the strongest independent factors associated with alcohol underreporting in this population. The use of PEth in addition to self-reported alcohol use resulted in 4-fold and 3-fold increases in MetALD and ALD diagnoses, respectively. Male sex, aspartate aminotransferase, mean corpuscular volume, high-density lipoprotein cholesterol, and MRI-derived proton density fat fraction were the strongest independent factors associated with higher PEth. PEth and self-reported alcohol use showed a moderate positive correlation, while the agreement was low.

Conclusions: PEth may objectively quantify alcohol use and help identify SLD subcategories alongside clinical history, reducing diagnostic misclassification.

Impact and implications: The current subclassification of steatotic liver disease (SLD) relies on self-reported alcohol use, which is frequently limited by patient underreporting, potentially leading to diagnostic misclassification. In this study of 391 community-dwelling adults with overweight/obesity and SLD assessed by advanced MRI methods, we found that 15.9% (95% CI 12.2%-19.5%) of individuals with SLD underreported alcohol use based on their phosphatidylethanol (PEth) levels. Male sex, absence of type 2 diabetes, and White race were the strongest independent factors associated with alcohol underreporting in this population. The incorporation of PEth alongside self-reported alcohol use resulted in a 4-fold increase in MetALD diagnoses and a 3-fold increase in ALD diagnoses. These findings support the clinical utility of PEth as a direct, quantitative, objective alcohol biomarker which may help clinicians identify SLD subcategories and differentiate between its metabolic and alcohol-related etiologies.

Keywords: ALD; NAFLD; alcohol drinking; biomarkers; ethanol; fatty liver; obesity.