Phosphatidylethanol and self-reported alcohol intake to subclassify in individuals at risk of steatotic liver disease: an analysis of data from a prospective cohort study.

BACKGROUND

Phosphatidylethanol is a direct biomarker of alcohol consumption within the past 1-4 weeks, making it a potential tool in the subclassification of patients with steatotic liver disease. However, the clinical utility of phosphatidylethanol among individuals at risk of steatotic liver disease remains to be established. We aimed to investigate the correlation between phosphatidylethanol and self-reported alcohol intake among individuals at risk of steatotic liver disease due to excessive alcohol consumption or metabolic dysfunction.

METHODS

We used data from a single-centre, prospective study that was conducted at Odense University Hospital (Odense, Denmark), designed to investigate use of non-invasive markers for screening for fibrosis. We analysed data for at-risk participants aged 30-75 years from the general population with a history of ongoing or previous excessive alcohol use (alcohol group) or metabolic dysfunction without excessive alcohol use (metabolic group). Participants self-reported past 1-week and 3-month average alcohol intake, and completed the Alcohol Use Disorders Identification-Consumption (AUDIT-C) questionnaire. The presence of hepatic steatosis (controlled attenuation parameter ≥248 dB/m), cardiometabolic risk factors and past 3-month alcohol intake were used to classify participants as having metabolic dysfunction-associated steatotic liver disease (MASLD; <20 g [females] or <30 g [males] per day), metabolic and alcohol-related liver disease (MetALD; 20-49 g or 30-59 g per day), or alcohol-related liver disease (ALD; ≥50 g or ≥60 g per day). Phosphatidylethanol was quantified with liquid chromatography-mass spectrometry according to standard procedures. We assessed correlations and concordance between phosphatidylethanol and self-reported alcohol intake. Underestimation of alcohol intake was defined as a low self-reported intake (<20 g [females] or <30 g [males] per day) but phosphatidylethanol of at least 80 ng/mL or a moderate-high self-reported intake (20-49 g or 30-59 g per day) but phosphatidylethanol 200 ng/mL or higher. We also developed a decision tree to guide clinical use of phosphatidylethanol testing on the basis of self-reported intake and AUDIT-C.

FINDINGS

1482 individuals in the alcohol group and 1442 in the metabolic group recruited between Oct 9, 2017, and Dec 9, 2022, were included in this analysis. Median phosphatidylethanol concentration was 172 ng/mL (IQR 45-434) in the alcohol group and 11 ng/mL (5-37) in the metabolic group. Phosphatidylethanol correlated with past 1-week self-reported intake (r=0·638 [95% CI 0·600-0·676] in the alcohol group vs r=0·655 [0·623-0·688] in the metabolic group), and the average preceding 3-months self-reported intake (r=0·628 [95% CI 0·586-0·669] vs r=0·725 [0·697-0·753]). 586 (39·5%) of 1482 participants in the alcohol group and 160 (11·1%) of 1442 participants in the metabolic group underestimated alcohol intake on the basis of a higher phosphatidylethanol concentration than self-reported intake. Fewer than 1% of participants (ten [0·7%] in the alcohol group and two [0·1%] in the metabolic group) with a high self-reported intake (≥50 g per day for females and ≥60 g per day for males) had phosphatidylethanol less than 20 ng/mL. Across both the alcohol and metabolic groups, 1433 participants had MASLD, of whom 559 (39·0%) had phosphatidylethanol concentrations indicative of either MetALD or ALD based on current recommended thresholds (≥20 ng/mL). For the 2042 participants with steatotic liver disease, phosphatidylethanol testing was diagnostically redundant for 812 (39·8%) participants who either had a self-reported alcohol intake corresponding to MASLD and a low AUDIT-C (612 participants), or who had a self-reported alcohol intake corresponding to ALD (200 participants).

INTERPRETATION

Phosphatidylethanol reveals substantial underestimation of alcohol intake, especially in those with a history of excessive alcohol consumption. Incorporating phosphatidylethanol into diagnostic steatotic liver disease algorithms could aid in patient subclassification.

FUNDING

Novo Nordisk Foundation.