Detection of Potential MetALD and ALD Using Phosphatidylethanol in a Large Multicenter MASH Trial Screening Cohort.

Authors

Mazen Noureddin, Jörn M Schattenberg, Rashmee Patil, Elizabeth W Brombosz, Gražina Binkauskiene, Michelle Mazuranic, Laura Ladron de Guevara Cetina, Marcelo Kugelmas, Aasim Sheikh, John Poulos, Sudha Kodali, Brian P Lee, Juan Pablo Arab, Naim Alkhouri

Published in

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. Aug 25, 2026. Epub Aug 25, 2026.

Abstract

Accurate distinction between metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and the overlap MetALD is of utmost importance. Due to the potential for underreporting in alcohol use surveys, phosphatidylethanol (PEth) is increasingly utilized in clinical trials to rule out MetALD or ALD. This study examines the prevalence of elevated PEth and its effectiveness in separating phenotypes with dominant MASLD or MetALD/ALD in the clinical trial setting.
A multicenter database of patients screened for enrollment in clinical trials for MASLD pharmacologic therapies was reviewed, from which patients with PEth results were identified, then further stratified into low (<20 ng/mL), moderate (20-<100 ng/mL), or high (≥100 ng/mL) alcohol intake groups.
Among 2870 patients with baseline PEth data, 2560 (89%) had low, 168 (6%) had moderate, and 142 (5%) had high PEth levels, including 92 with PEth ≥200 ng/mL. Higher hemoglobin A1C (HbA1c) was associated with lower PEth (p<0·001). AST (p<0.001), ALT (p<0.001), and gamma-glutamyl transferase (GGT; p<0.001) were elevated in patients with higher PEth results. Indeterminate fibrosis-4 scores were more prevalent in patients with PEth ≥100 ng/mL (p<0.001). In multivariable analysis, PEth ≥20 ng/mL was associated with higher GGT (per 10 U/L, aOR, 1.04; 95% CI, 1.03-1.06; p<0.001) and lower HbA1c (aOR, 0.68; 95% CI, 0.60-0.78; p<0.001).
In this prospective multicenter cohort of participants screened for MASLD clinical trials with systematically collected PEth, 11% had PEth ≥20 ng/mL, suggesting a level of alcohol consumption that may warrant further clinical evaluation for possible MetALD or ALD.

PMID:
42641902
Bibliographic data and abstract were imported from PubMed on 26 Aug 2026.

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