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Liver tissue proteins improve the accuracy of plasma proteins as biomarkers in diagnosing metabolic dysfunction-associated steatohepatitis
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  • Achuthan Sourianarayanane,
  • Michelle Salemi,
  • Brett Phinney,
  • Arthur McCullough
Achuthan Sourianarayanane
Medical College of Wisconsin Department of Medicine

Corresponding Author:[email protected]

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Michelle Salemi
University of California Davis
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Brett Phinney
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Arthur McCullough
Cleveland Clinic
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Abstract

Background: Biomarkers for metabolic dysfunction-associated steatohepatitis (MASH) have been considered based on proteomic and lipidomic data from plasma and liver tissue without clinical benefits. This study evaluated proteomics-based plasma and liver tissue biomarkers collected simultaneously from patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: Liver tissue samples and plasma samples were collected during liver biopsy for diagnosis. Untargeted proteomics was performed on 64 patients with MASLD. Results: Twenty plasma proteins were up or downregulated in patients with MASH compared with those without MASH. The biomarkers utilizing the best combinations of these plasma proteins had an area under the receiver operating curve (AUROC) of 0.671 for detecting those with MASH compared with those without it. However, none of the 20 plasma proteins were represented among the significantly regulated liver tissue proteins in patients with MASH. Ten of them displayed a trend and relevance in liver tissue with MASLD progression. These ten plasma proteins had an AUROC of 0.793 for MASH identification and higher positive and negative predictive values. Conclusion: The plasma and liver protein expressions of patients with MASH were not directly comparable. Plasma protein biomarkers that are also expressed in liver tissue can help improve MASH detection.
Submitted to Clinical Applications
27 Mar 2024Review(s) Completed, Editorial Evaluation Pending
27 Mar 2024Editorial Decision: Revise Major
12 Jun 2024Review(s) Completed, Editorial Evaluation Pending
12 Jun 20241st Revision Received
19 Jul 2024Editorial Decision: Accept