Z Gastroenterol 2025; 63(01): e18
DOI: 10.1055/s-0044-1801041
Abstracts │ GASL
Poster Visit Session II
CLINICAL HEPATOLOGY, SURGERY, LTX 14/02/2025, 02.20pm – 03.15pm

Novel predictors of major adverse liver outcomes employing the UK Biobank

Sriram Balasubramani
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Anna Sophie Karl
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Christina Barbara Schrader
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Malin Fromme
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Katharina Remih
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Pavel Strnad
1   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
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    Background: Since liver disease is often clinically unapparent, plasma biomarkers predicting the future development of major adverse liver outcomes (MALO) are urgently needed. Therefore, we assessed the usefulness of a novel, proximity extension assay (PEA)-based high-throughput proteomic technique to predict MALOs.

    Methods: PEA quantified>2900 plasma proteins in 53003 participants (490 MALOs) from the UK Biobank (UKB) and in a validation cohort of 287 subjects with severe alpha1-antitrypsin deficiency (30 MALOs). In UKB, we also studied two high-risk sub-cohorts: obese and diabetic subjects. PEA-based values were compared to measurements with routine techniques. Differential abundance analysis and multivariable logistic regression were used to discover predictors.

    Results: In UKB, PEA-based measurement of gamma-glutamyl transferase (GGT) and aspartate aminotransferase correlated well with routine values (r=0.91/0.68). After adjustment for multiple testing,>1700 plasma proteins significantly differed between subjects with vs. without future MALOs. The most altered proteins were predominantly of liver, intestine or lymphoid tissue origin and remained significant in the diabetic/obese sub-cohort. Five proteins, ADAMTS-like protein 2, polymeric immunoglobulin receptor, integrin beta-like protein 1, thrombospondin 2, and insulin-like growth factor binding protein 7 robustly predicted future MALOs at least as good GGT that constituted the best routinely available predictor. They were particularly useful in the high-risk sub-cohorts, yielding AUROCs 0.80-0.86. In the validation cohort, all novel biomarkers associated positively with degree of liver fibrosis and numerically outperformed GGT in predicting MALOs (AUROCs:0.86-0.95).

    Conclusion: PEA-based proteomic assessment is a promising source of non-invasive predictors of MALO development.


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    Publication History

    Article published online:
    20 January 2025

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