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| Autori principali: | , , , , , , , , , , , , , , |
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| Natura: | Artículo Open Access |
| Pubblicazione: |
Wiley
2026
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| Accesso online: | https://onlinelibrary.wiley.com/doi/10.1111/apt.70656 |
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- Affinity Proteomics‐Based Non‐Invasive Detection of Clinically Significant Liver Disease Sriram Balasubramani Katharina Remih Anna Sophie Karl Julia Alexandra Borchert Christina Schrader Malin Fromme Can Kayatekin Bailin Zhang Mikhail Levit Pavithra Krishnaswami Louise E. van Eekeren Leo A. B. Joosten Twan Otten Petra Tomanová Pavel Strnad Alimentary Pharmacology & Therapeutics ABSTRACT Background Non‐invasive biomarkers predicting major adverse liver outcomes (MALO) are urgently needed. Aims We assessed a novel, proximity extension assay‐based high‐throughput targeted proteomics. Methods Plasma proteomic data (> 2900 proteins) and clinical information were accessed from the population‐based UK Biobank cohort, comprising ~52,000 individuals with a median follow‐up of > 10 years, including obese (~12,700) and diabetic (~1500) participants. Validation cohorts comprised 287 participants with severe alpha1‐antitrypsin deficiency (Pi*ZZ genotype), and 960 people living with HIV, who underwent liver stiffness measurement (LSM) via transient elastography. Selected proteomic parameters were compared to routine measurements. Bayes‐moderated linear models (covariates: age and sex) assessed the differential abundance. Logistic regression was used to develop and validate a prognostic score. Results Routine gamma‐glutamyltransferase (GGT) and aspartate aminotransferase (AST) strongly correlated with proteomic measurements ( r = 0.92 and r = 0.71, respectively). Similarly, proteomic‐based thrombospondin‐2 levels correlated with immunoassay‐based values ( r = 0.85). Twenty proteins were consistently associated with future MALOs/increased liver stiffness in all cohorts. A novel five‐component proteomic score derived from the UK Biobank cohort demonstrated 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), with stable performance in obese and diabetic subcohorts. In people living with HIV and alpha1‐antitrypsin deficiency patients, all five components increased across fibrosis stages and the proteomic score outperformed AST‐to‐platelet‐ratio/Fibrosis‐4 index in predicting significant LSM‐based liver fibrosis. Conclusions We identify a new proteomic score comprising epithelial/hepatic stellate cell markers that yields a robust predictive performance across different liver disease aetiologies. Thereby, we demonstrate the usefulness of emerging proteomic techniques in hepatology. Trial Registration The registry study is listed at ClinicalTrials.gov (NCT02929940) 10.1111/apt.70656 http://creativecommons.org/licenses/by/4.0/