Evidence map›Paper›PMID 41992602›Full record

Observational studyAlimentary pharmacology & therapeutics2026

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 and 5 more

Registry-linked trialAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Alimentary pharmacology & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02929940 (Multi-center Study of the Liver Disease in European Patients With alpha1-antitrypsin Deficiency), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02929940 unknown statusnot on this map

Multi-center Study of the Liver Disease in European Patients With alpha1-antitrypsin Deficiency

Typeobservational_patient_registrySponsorRWTH Aachen UniversityRan2015 to 2020Enrolled500Conditionsalpha1-antitrypsin DeficiencyArmsNo intervention
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Sriram BalasubramaniMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen, Aachen, Germany.
Katharina RemihMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen, Aachen, Germany.
Anna Sophie KarlMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen, Aachen, Germany.
Julia Alexandra BorchertMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen, Aachen, Germany.
Christina SchraderMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen, Aachen, Germany.
Malin FrommeMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen, Aachen, Germany.ORCID 0000-0003-0382-5705
Can KayatekinSanofi, Cambridge, Massachusetts, USA.
Bailin ZhangSanofi, Cambridge, Massachusetts, USA.
Mikhail LevitSanofi, Cambridge, Massachusetts, USA.
Pavithra KrishnaswamiSanofi, Cambridge, Massachusetts, USA.
Louise E van EekerenDepartment of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
Leo A B JoostenDepartment of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
Twan OttenDepartment of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
Petra TomanováPrague University of Economics and Business, Prague, Czech Republic.
Pavel StrnadMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen, Aachen, Germany.

Funding

Arrowhead PharmaceuticalsCSL BehringEuropean Association for the Study of the Liver SFB1382(ID403224013)European Association for the Study of the Liver STR1095/6-1German Liver Foundation
6 · The paper itself

Abstract

backgroundNon-invasive biomarkers predicting major adverse liver outcomes (MALO) are urgently needed.

aimsWe assessed a novel, proximity extension assay-based high-throughput targeted proteomics.

methodsPlasma 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.

resultsRoutine 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.

conclusionsWe 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 registrationThe registry study is listed at ClinicalTrials.gov (NCT02929940).

Indexed as

Liver DiseasesProteomicsAdultalpha 1-Antitrypsin DeficiencyAspartate AminotransferasesBiomarkersCohort StudiesElasticity Imaging TechniquesFemalegamma-GlutamyltransferaseHumansMaleMiddle AgedUnited KingdomAspartate AminotransferasesBiomarkersgamma-Glutamyltransferasealpha‐1 antitrypsin deficiencynon‐invasive liver testPEAplasma proteomicsUK Biobank

Identifiers

PMID41992602
PMCPMC13251591

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.