A-133 Routine Chemistry Overlooks MASLD: A Metabolomic Assessment Using OWLiver

Abstract

Metabolic dysfunction–associated steatotic liver disease (MASLD) is highly prevalent yet frequently underrecognized in clinical practice. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are commonly used screening tools; however, their sensitivity is limited, as patients with clinically significant disease may present with values within reference intervals. OWLiverTM, a lipidomic-based serum assay, provides risk stratification for MASLD by evaluating metabolomic signatures associated with steatohepatitis and fibrosis. This study assessed the concordance and discordance between OWLiverTM MASLD diagnosis and traditional transaminase measurements in a real-world clinical laboratory population. A retrospective analysis was performed on 17,505 patients who underwent OWLiverTM testing at a CAP/CLIA-certified U.S. clinical laboratory between January 2024 and January 2026. OWLiverTM results were categorized as steatosis/no MASLD, metabolic dysfunction–associated steatohepatitis (MASH) F0–F1, or MASH with significant fibrosis (F=2). ALT and AST reference intervals were sex-specific and updated on August 1, 2025, following implementation of a new Abbott Alinity reagent (male ALT <55 U/L; female ALT <55 U/L pre-update and<45, <34 U/L respectively post-update; AST male 5–51 U/L and female 5–34 U/L, and 11-34 post-updated). Concordance and discordance between OWLiverTM classification and transaminase status were evaluated. Primary analyses included:proportion of patients with MASH (F0–F1) or MASH with significant fibrosis (F=2) with normal ALT or ASTproportion of elevated ALT or AST results among patients classified as steatosis/no MASLDevaluation of alternative reference ranges to optimize sensitivity and specificity using AUROC analysis The cohort was 57% female with a mean age of 60 ± 15 years. Among all patients:9.4% were classified as MASH (F0–F1)10.4% were classified as MASH with significant fibrosis (F=2)11% had elevated ALT values Discordance analysis demonstrated substantial limitations of transaminase-based screening:65.5% of MASH (F0–F1) patients and 61.2% of MASH with significant fibrosis patients had normal ALT55.5% of MASH (F0–F1) patients and 49.5% of MASH with significant fibrosis patients had normal AST Conversely:4.45% of patients with elevated ALT were classified as steatosis/no MASLD by OWLiverTM.5.29% of patients with elevated AST were classified as steatosis/no MASLD by OWLiverTM. ALT elevation demonstrated limited sensitivity for detecting OWLiverTM-identified MASH, identifying only [37 %] of individuals. Traditional liver chemistries alone fail to identify a substantial proportion of patients with MASH and significant fibrosis. In this large real-world cohort, OWLiverTM identified many patients with steatohepatitis who would not have been detected using ALT and AST screening alone. These findings highlight the limitations of transaminase-based screening and support the clinical utility of lipidomic risk profiling to improve MASLD detection and risk stratification in routine clinical practice.