Editorial: Revolutionising Steatotic Liver Disease Diagnosis With Phosphatidylethanol

Abstract

The recent re-naming and reclassification of ‘non-alcoholc fatty liver disease (NAFLD)’ to steatotic liver disease (SLD) subcategories aims to clarify the different aetiologies associated with liver fat accumulation, particularly alcohol consumption and/or metabolic dysfunction [1]. A novel entity, coined as ‘metabolic and alcohol related/associated liver disease (MetALD)’ was introduced to capture individuals whose alcohol intake exceeds traditional NAFLD thresholds but not yet meet the thresholds of alcohol-related liver disease (ALD) [1]. The shift in terminology highlights the complexity between alcohol consumption and metabolic dysfunction on pathophysiology, natural course and treatment implications in SLD. Accurate quantification of alcohol consumption is therefore crucial. However, current alcohol consumption estimations rely solely on patients' self-report, where underreporting is common leading to misclassification. An objective alcohol biomarker is pivotal in providing an accurate assessment of an individual's drinking pattern. Phosphatidylethanol (PEth) levels in the blood is a promising biomarker that has garnered significant attention in the field of alcohol research. Being an abnormal phospholipid that is only formed in the presence of ethanol, not only it is easily measured in blood, but it also has a long detection window lasting for 2–4 weeks.

Tavaglione et al. conducted a cross-sectional study to compare PEth with other indirect alcohol biomarkers for the diagnosis of MetALD versus metabolic dysfunction-associated steatotic liver disease (MASLD) in 374 subjects who were obese (body mass index [BMI] ≥ 25 kg/m²) with imaging-confirmed SLD (magnetic resonance imaging-proton density fat fraction or transient elastography). Alcohol use was quantified using a questionnaire (AUDIT score and Lifetime Drinking History) and DSM-V criteria. PEth was shown to have high diagnostic accuracy in the detection of MetALD (AUROC 0.81, 95% CI 0.73–0.89) with the optimal cut-off level of 25 ng/mL. It showed superiority over traditional biomarkers including aspartate aminotransferase/alanine aminotransferase ratio, mean corpuscular volume, gamma glutamyltransferase and ALD/NAFLD index (p < 0.05) in diagnosing MetALD in a cohort of SLD. A positive linear correlation between PEth levels and daily alcohol intake and AUDIT score was also demonstrated [2].

This paper provides timely insight into the role of using biomarkers in redefining subcategories of SLD. The results align with recent compelling evidence affirming the accuracy of utilising blood PEth levels to predict the quantity of alcohol consumption [3], and the recent joint position statement to recommend its use [4]. Given that PEth is derived from human erythrocytes, the precision of PEth measurements may be impacted by conditions such as cirrhosis, anaemia, or hypersplenism [5]. Similarly, variations in PEth levels may be observed between patients engaging in binge drinking and those with chronic heavy alcohol consumption, as well as various BMIs. Delving deeper into these aspects through additional research can enhance the validation of PEth's clinical utility. Variability of PEth levels across diverse ethnic groups also presents a valuable opportunity for future research.

The new SLD classification aims to enhance comprehension of various liver conditions, including their epidemiology, diagnosis, progression and management strategies. Incorporating an objective biomarker into disease classification can improve the clinical validity and applicability of this new system, ultimately enhancing clinical decision-making and patient outcomes.

Karen Cheuk-Ying Ho: writing – original draft. Lung-Yi Mak: writing – review and editing, supervision.

This article is linked to Tavaglione et al papers. To view these articles, visit https://doi.org/10.1111/apt.18506 and https://doi.org/10.1111/apt.70006.