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The MetALD-ALD Prediction Index: A Phosphatidylethanol-Driven Biomarker Panel for Identifying Individuals With
Federica Tavaglione1, Juan Vaz2, Oveis Jamialahmadi3
1MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, California.
Background & Aims:
Phosphatidylethanol (PEth) is a direct, objective alcohol biomarker for detecting excessive alcohol use in steatotic liver disease, including metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-associated liver disease (ALD). However, its use in routine clinical practice may be limited by cost and accessibility. This study aimed to develop a novel, accurate, and scalable indirect alcohol biomarker panel to screen for MetALD-ALD in general population settings.
Methods:
The derivation cohort consisted of 503 community-dwelling adults with overweight/obesity and steatotic liver disease residing in Southern California, all of whom prospectively underwent magnetic resonance imaging/magnetic resonance elastography assessment and PEth testing. The optimal predictive model was developed using bidirectional stepwise logistic regression and internally validated using 2000 bootstrap samples. The outcome was the presence of MetALD-ALD, defined by incorporating PEth. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC). External validation was conducted in an independent, population-based Swedish cohort of 1777 individuals with available PEth measurements.
Results:
In the derivation cohort, the mean (standard deviation) age and body mass index were 51 (13) years and 32.9 (5.8) kg/m2, respectively. The final predictive model, termed the MetALD-ALD Prediction Index (MAPI), included sex, mean corpuscular volume, gamma-glutamyltransferase, high-density lipoprotein cholesterol, and hemoglobin A1c. MAPI demonstrated good performance in both derivation and validation cohorts (AUROC, 0.76 and 0.75, respectively). MAPI was the top-performing model among all commonly used indirect alcohol biomarkers, based on AUROC.
Conclusions:
MAPI is a novel, accurate, and scalable biomarker panel for detecting MetALD-ALD. MAPI may guide confirmatory PEth testing in clinical practice and be leveraged in observational cohort studies lacking PEth measurements, as well as in clinical trials.
