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Affinity Proteomics-Based Non-Invasive Detection of Clinically Significant Liver Disease.

Sriram Balasubramani1, Katharina Remih1,2, Anna Sophie Karl1

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Summary

A novel proteomic score accurately predicts major adverse liver outcomes (MALO) and liver fibrosis. This new biomarker shows superior performance compared to existing scores, offering a promising tool for hepatology.

Keywords:
PEAUK Biobankalpha‐1 antitrypsin deficiencynon‐invasive liver testplasma proteomics

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Area of Science:

  • Proteomics
  • Biomarker Discovery
  • Hepatology

Background:

  • Non-invasive biomarkers for predicting major adverse liver outcomes (MALO) are critically needed.
  • Existing biomarkers have limitations in accuracy and scope.
  • Emerging proteomic technologies offer new avenues for biomarker development.

Purpose of the Study:

  • To assess a novel proximity extension assay-based high-throughput targeted proteomics approach.
  • To identify and validate proteomic biomarkers for predicting MALO and liver fibrosis.
  • To compare the predictive performance of a novel proteomic score against established clinical scores.

Main Methods:

  • Utilized plasma proteomic data (>2900 proteins) and clinical information from the UK Biobank cohort (~52,000 individuals) with >10 years of follow-up.
  • Validated findings in cohorts of individuals with alpha-1-antitrypsin deficiency (n=287) and people living with HIV (n=960), including liver stiffness measurements (LSM).
  • Employed Bayes-moderated linear models and logistic regression to develop and validate a five-component proteomic prognostic score.

Main Results:

  • Routine liver enzymes (GGT, AST) showed strong correlations with proteomic measurements.
  • A novel five-component proteomic score achieved superior predictive power for MALOs (AUROC=0.84) compared to AST-to-platelet-ratio index (AUROC=0.73) and Fibrosis-4 index (AUROC=0.72).
  • The proteomic score demonstrated robust performance across diverse liver disease etiologies, including obese, diabetic, HIV-infected, and alpha-1-antitrypsin deficiency patient cohorts.

Conclusions:

  • A new proteomic score, comprising epithelial/hepatic stellate cell markers, provides robust prediction of liver disease outcomes.
  • This proteomic score outperforms current non-invasive markers for predicting MALO and liver fibrosis.
  • Highlights the utility of advanced proteomic techniques in advancing hepatology and liver disease management.