Correlation of Plasma and Liver Tissue Proteomics for Plasma Biomarkers in Metabolic Dysfunction-Associated Steatotic Liver Disease

Diagnosing metabolic dysfunction-associated steatohepatitis (MASH) within the spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD) remains challenging. This study evaluates the relationship between plasma proteins and their liver tissue counterparts to assess their potential as diagnostic biomarkers for MASH. An untargeted proteomic analysis was performed on paired liver tissue and plasma samples obtained during biopsies from 7 controls and 64 MASLD patients. Plasma proteins that showed significant correlations with their liver counterparts and exhibited consistent gradients across progressive MASLD stages were evaluated as biomarkers. The study found that liver tissue proteomics showed a strong correlation with MASLD histological severity. Of 356 plasma proteins, 30 showed significant positive correlations (<i>r</i> > 0.5, <i>p</i> < 0.01) with their liver tissue counterparts. Eight proteins exhibited consistent changes across disease stages and distinguished MASH from non-MASH with an area under the receiver operating curve (AUROC) of 0.786 and advanced fibrosis from nonfibrosis cases with an AUROC of 0.874. In conclusion, a limited subset of plasma proteins reflects liver proteomic changes and may serve as biomarkers for distinguishing MASH and fibrosis stages within MASLD.