Phosphatidylethanol Testing in Clinical Practice for the Identification of MASLD Subtypes

Phosphatidylethanol (PEth) testing is increasingly recognized as a valuable tool in clinical practice for distinguishing subtypes of steatotic liver disease (SLD), particularly in the context of the updated 2023 nomenclature. Accurate identification of SLD subtypes — MASLD (metabolic dysfunction–associated SLD), ALD (alcohol-associated liver disease), and MetALD (metabolic dysfunction and alcohol-associated liver disease) — is essential for tailoring treatment strategies to individual patients, and PEth testing plays a critical role in quantifying alcohol intake objectively.

### Why PEth Testing is Important in SLD Classification

1. **Objective Alcohol Intake Measurement**: PEth is a direct biomarker of alcohol consumption, formed in the presence of ethanol in red blood cells. It provides a reliable indication of alcohol use over the prior 2–4 weeks, offering a more objective assessment compared to self-reported alcohol intake, which can be influenced by underreporting or recall bias.

2. **Threshold-Based Subtype Differentiation**: The updated SLD classification relies on weekly alcohol thresholds to differentiate between MASLD, MetALD, and ALD:

• MASLD vs. MetALD: >140 g/week for women or >210 g/week for men.
• MetALD vs. ALD: >350 g/week for women or >420 g/week for men.

PEth levels can help determine whether a patient’s alcohol consumption exceeds these thresholds, ensuring accurate subtype classification.

3. **Synergistic Role of Alcohol and Metabolic Dysfunction**: MetALD represents a hybrid subtype where both metabolic dysfunction and alcohol intake contribute to liver damage. PEth testing can help identify patients whose alcohol use is significant enough to shift their diagnosis from MASLD to MetALD, emphasizing the need for tailored interventions addressing both metabolic and alcohol-related factors.

### Advantages of PEth Testing in Clinical Practice

• **High Sensitivity and Specificity**: PEth testing has superior sensitivity and specificity compared to other alcohol biomarkers (e.g., ethyl glucuronide [EtG], carbohydrate-deficient transferrin [CDT]). It is particularly useful for detecting moderate-to-heavy alcohol use.
• **Correlation with Alcohol Dose**: PEth levels correlate strongly with the amount of alcohol consumed, making it a quantitative tool for assessing whether a patient’s intake exceeds the thresholds for SLD subtype differentiation.
• **Non-Invasive and Convenient**: PEth testing involves a simple blood draw, making it a practical option for routine clinical use.

### Clinical Implementation of PEth Testing

1. **Routine Use in SLD Diagnosis**: Incorporating PEth testing into the diagnostic workup for patients with suspected SLD can improve the accuracy of subtype classification and guide treatment decisions.

2. **Monitoring Alcohol Intake**: For patients with MetALD or ALD, PEth testing can be used to monitor adherence to alcohol reduction or abstinence goals during treatment.

3. **Integration with Other Biomarkers**: PEth testing can complement other clinical assessments, such as liver function tests, imaging, and metabolic evaluations, to provide a comprehensive picture of disease etiology and progression.

### Limitations and Considerations

• **Cost and Accessibility**: PEth testing may not be universally available or covered by all healthcare systems, potentially limiting its use in some settings.
• **Interpretation Challenges**: While PEth provides a reliable measure of alcohol intake, clinicians must consider individual variability in alcohol metabolism and the potential influence of comorbid conditions when interpreting results.

### Conclusion

Phosphatidylethanol testing represents a powerful tool for identifying MASLD subtypes and guiding personalized management strategies for steatotic liver disease. Its ability to objectively quantify alcohol intake is particularly important in distinguishing MASLD from MetALD and ALD, ensuring that patients receive appropriate interventions targeting both metabolic dysfunction and alcohol-related liver damage. As clinical awareness of the updated SLD classification grows, PEth testing is likely to become a cornerstone of diagnostic and therapeutic decision-making in liver disease management.