Metabolic dysfunction–associated steatotic liver disease (MASLD) and alcohol–associated liver disease (ALD) are leading causes of chronic liver injury with overlapping clinical and histological presentations. This study evaluated a composite histologic pattern, termed the Alcohol Liver Pathology Signature (ALPS), for potential use in the differential diagnosis of ALD and MASLD and to explore potential clinical and demographic correlates.
In this retrospective diagnostic-accuracy study, we reviewed 292 liver biopsies performed between 2021 and 2023. ALPS comprised five histologic features: ductular reaction, bile stasis, neutrophilic satellitosis, portal inflammation, and advanced fibrosis (stage 3–4). Cases were categorized as absent (0–1 features), partial (2–3 features), or full (4–5 features). ALPS performance was then further evaluated in an independent temporal validation cohort of de-identified, mixed, and blindly reviewed liver biopsies collected between 2024 and 2025.
MASLD was the most common diagnosis (25.3%), whereas ALD accounted for 4.8%. Full ALPS was present in 92.8% of clinically diagnosed ALD cases. In MASLD, individual ALPS features were common, but only 20.3% showed full ALPS, corresponding to 79.7% specificity for distinguishing clinically diagnosed ALD from MASLD. The independent temporal validation cohort showed findings consistent with those of the original cohort. Finally, within MASLD, full ALPS was more frequent in African American than non-African American patients (29.2% vs. 3.8%).
ALPS may serve as a histologic prompt for further assessment of potential alcohol exposure but should not be considered etiologically specific. Prospective validation incorporating objective measures of alcohol exposure is warranted.
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