MASLD clinical trial screening using phosphatidylethanol (PEth) identified potentially relevant alcohol consumption in 11% of participants, highlighting the biomarker’s potential role in distinguishing metabolic dysfunction associated steatotic liver disease from possible MetALD or alcohol associated liver disease.
Accurately differentiating these liver disease phenotypes is important, but reliance on self reported alcohol consumption may be affected by underreporting. Researchers therefore examined the prevalence of elevated PEth and its ability to distinguish phenotypes dominated by MASLD from those potentially involving MetALD or alcohol associated liver disease (ALD).
The multicentre study reviewed patients screened for enrolment in clinical trials of pharmacological therapies for MASLD. Participants with available PEth measurements were categorised as having low, moderate, or high levels using thresholds of <20 ng/mL, 20–<100 ng/mL, and ≥100 ng/mL, respectively.
Among 2,870 participants with baseline PEth data, 2,560, or 89%, had concentrations below 20 ng/mL. Moderate PEth levels were identified in 168 participants, or 6%, while 142, or 5%, had concentrations ≥100 ng/mL. This meant that 11% overall had PEth ≥20 ng/mL. Among those with high concentrations, 92 had PEth ≥200 ng/mL.
Higher PEth levels were associated with increased aspartate aminotransferase, alanine aminotransferase, and gamma glutamyl transferase (GGT) levels: all p<0.001. Indeterminate fibrosis 4 scores were also more prevalent among participants with PEth ≥100 ng/mL: p<0.001.
Multivariable analysis showed that PEth ≥20 ng/mL was associated with higher GGT: adjusted odds ratio (aOR): 1.04 per 10 U/L; 95% CI: 1.03–1.06; p<0.001. Elevated PEth was also associated with lower glycated haemoglobin: aOR: 0.68; 95% CI: 0.60–0.78; p<0.001.
The researchers concluded that systematically collected PEth identified alcohol consumption potentially warranting further clinical evaluation for MetALD or ALD in more than 1 in 10 participants screened for MASLD clinical trials.
The findings highlight the potential value of PEth when characterising liver disease phenotypes in the clinical trial setting, particularly where accurately distinguishing MASLD from alcohol related or overlapping disease is important.
Reference
Noureddin M et al. Detection of Potential MetALD and ALD Using Phosphatidylethanol in a Large Multicenter MASH Trial Screening Cohort. Clin Gastroenterol Hep. 2026.
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