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

Abstract

We thank Abubakr and colleagues [1] for their supportive comments on our recently published work, where we show that phosphatidylethanol (PEth) is a precise, quantitative, objective alcohol biomarker for differentiating metabolic dysfunction and alcohol-related liver disease (MetALD) from metabolic dysfunction-associated steatotic liver disease (MASLD). Notably, PEth exhibited robust diagnostic accuracy, with an AUROC of 0.81 (95% CI 0.73–0.89) and an optimal cut-off value of 25 ng/mL, outperforming traditional alcohol biomarkers [2]. The study population included over 300 community-dwelling individuals with overweight or obesity and steatotic liver disease (SLD) assessed through advanced magnetic resonance imaging (MRI) techniques, namely MRI-PDFF and MRE, from the greater San Diego area [3].

PEth is a direct alcohol biomarker that forms exclusively in the presence of ethanol, resulting in high sensitivity and specificity with minimal false positives [4]. As we previously discussed [5], the dynamics of PEth formation and degradation at the level of human erythrocyte membrane lead one to consider that conditions such as anaemia, advanced stages of liver disease and drinking patterns may influence PEth levels. However, limited studies have specifically examined the impact of these conditions on PEth variability. Additional research is required to investigate the performance of PEth, as well as the underlying mechanisms governing its formation and degradation across different stages of SLD and drinking patterns.

Similarly, since body mass index (BMI) is inversely correlated with blood alcohol concentration [6], it is reasonable to speculate that obesity may affect PEth levels. However, due to the paucity of studies specifically exploring the diagnostic accuracy of PEth in individuals with both excessive alcohol use and underlying metabolic dysfunction (i.e., MetALD), further studies are needed to fully address this question.

In conclusion, our study paves the way for a new and unexplored research field aimed at investigating the role of direct alcohol biomarkers, such as PEth, alongside self-reported alcohol use in the context of SLD. Further exploration is necessary to better understand their diagnostic accuracy and utility in clinical practice.

The authors' declarations of personal and financial interests are unchanged from those in the original article [2].

Federica Tavaglione: writing – review and editing, writing – original draft. Rohit Loomba: writing – original draft, writing – review and editing.

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.70008.