Letter on ‘Head-to-Head Comparison Between Phosphatidylethanol Versus Indirect Alcohol Biomarkers for Diagnosis of MetALD Versus MASLD: A Prospective Study’

Abstract

We read with great interest the study by Tavaglione et al. titled ‘Head-to-Head Comparison Between Phosphatidylethanol Versus Indirect Alcohol Biomarkers for Diagnosis of MetALD Versus MASLD: A Prospective Study’ [1]. The study provides a valuable insight into the use of phosphatidylethanol (PEth) as a non-invasive diagnostic marker in distinguishing metabolic dysfunction and alcohol–associated liver disease (MetALD) from metabolic dysfunction–associated steatotic liver disease (MASLD) through a cross-sectional analysis in a multiethnic population. The authors' emphasis on the practical use of PEth in clinical settings is both timely and crucial, as it helps fill an important gap in how we currently classify steatotic liver disease (SLD).

The authors also highlight the limitations of current questionnaires, such as the Alcohol Use Disorders Identification Test (AUDIT) and Lifetime Drinking History (LDH), including their lack of precision and impracticality in clinical settings. Given the strong diagnostic accuracy of PEth in detecting MetALD, as demonstrated in the study, it is crucial to further validate PEth across diverse patient populations, encompassing variations in race, age, disease stage and clinical settings, to solidify its role in routine clinical practice. Future research should focus on comparing PEth testing with other diagnostic modalities, including advanced imaging, genetic markers and emerging biomarkers, to enhance our understanding of its diagnostic accuracy in the identification of SLD.

While the study shows strong diagnostic accuracy for detecting MetALD (AUROC 0.81, 95% CI 0.73–0.89), it would be helpful to know how PEth performs at different stages of the disease. The study does not provide an in-depth exploration of the biological mechanisms underlying PEth's role in disease diagnosis. Additionally, a more thorough analysis of potential confounding factors, such as patterns of alcohol consumption, inter-individual variability in PEth half-lives, BMI differences and variations in liver function, could further enhance the diagnostic accuracy of PEth [2]. The study also fails to address potential limitations of PEth testing, such as the risk of false positives or false negatives in certain populations, as well as its cost-effectiveness relative to traditional indirect alcohol biomarkers and more invasive diagnostic techniques. Furthermore, a comparative analysis of PEth with emerging biomarkers, genetic tests and advanced imaging methods would provide a clearer understanding of its diagnostic accuracy and help establish its relative position among other available diagnostic tools.

The introduction of PEth testing into clinical practice has the potential to streamline the diagnostic process and provide robust support for clinical decision-making. A comprehensive understanding of this biomarker, coupled with large-scale, multicentre, longitudinal studies across diverse patient populations—encompassing varying stages of liver disease, alcohol consumption patterns, age groups and comorbidities—could facilitate more effective management of liver diseases associated with metabolic dysfunction and alcohol use. We look forward to further research in this area and the eventual integration of PEth as a critical biomarker in clinical settings to differentiate MetALD from MASLD.

Muhammad Abubakr: conceptualization, writing – original draft, writing – review and editing, project administration, visualization. Zuhair Abrar: conceptualization, writing – original draft, writing – review and editing, visualization. Muhammad Jawad Haider: conceptualization, writing – original draft, writing – review and editing, visualization. Saad Aslam Barqaat: conceptualization, writing – original draft, writing – review and editing, visualization.

The authors declare no conflicts of interest.

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.70018.