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Isolation and Enrichment of Liver Progenitor Subsets Identified by a Novel Surface Marker Combination
Published on: February 18, 2017
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Integrated liver-secreted and plasma proteomics identify a predictive model that stratifies MASH
William De Nardo1, Olivia Lee1, Yazmin Johari2
1Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Melbourne, VIC 3010, Australia.
Cell Reports. Medicine
|April 18, 2025
Summary
A new model using plasma proteins can identify individuals with obesity at higher risk for metabolic-associated steatohepatitis (MASH). This discovery offers a non-invasive method to stratify patients with metabolic-associated steatotic liver disease (MASLD) progression.
Area of Science:
- Hepatology
- Proteomics
- Metabolic Diseases
Background:
- Obesity is a primary risk factor for metabolic-associated steatotic liver disease (MASLD).
- MASLD can advance to metabolic-associated steatohepatitis (MASH), a condition lacking non-invasive risk stratification tools.
- Accurate MASH risk assessment is crucial for managing obesity-related liver complications.
Purpose of the Study:
- To investigate the proteomic changes in liver and plasma associated with MASLD progression.
- To identify novel biomarkers for stratifying MASH risk in obese individuals.
- To develop a predictive model for MASH in the context of obesity.
Main Methods:
- Proteomic analysis of liver-secretion medium from 96 human livers using mass spectrometry.
- Analysis of plasma proteomes from 266 obese individuals across the MASLD spectrum.
- Development and validation of the APASHA predictive model.
Main Results:
- Identified 107 differentially secreted proteins in MASH compared to non-pathological liver samples.
- Observed significant remodeling of the plasma proteome in MASH.
- The APASHA model (Apolipoprotein F, PCSK9, Afamin, S100A6, HbA1c, AZGP1) achieved an AUROC of 0.88 for MASH stratification.
Conclusions:
- The study details the evolution of liver-secreted and plasma proteins during MASLD progression.
- The APASHA model provides a validated, non-invasive tool for MASH risk stratification in obese patients.
- These findings offer a valuable resource for understanding liver protein secretion and MASH development.

