Evidence map›Paper›PMID 42809338›Full record

ArticleLiver international : official journal of the International Association for the Study of the Liver2026

Distinct Plasma Proteomic Signatures Distinguish MASLD From Non-Steatotic Individuals but Not From MetALD.

Niharika Jakhar, Tobias Seibel, Maria Mironova, Corinna Meeßen, Jan Clusmann, Yazhou Chen, Thriveni B Raju, Paul-Henry Koop, Juliette E Pearce, Ivan G Costa and 5 more

Registry-linked trialAbstract read
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In one paragraph

Article in Liver international : official journal of the International Association for the Study of the Liver, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02520609 (Dynamic Post-Prandial Metabolism in Patients With Non-Alcoholic Fatty Liver Disease), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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.

NCT02520609 completednot on this map

Dynamic Post-Prandial Metabolism in Patients With Non-Alcoholic Fatty Liver Disease

TypeobservationalSponsorNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Ran2015 to 2020Enrolled53ConditionsLiver Disease, Fatty Liver
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Niharika JakharMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.ORCID https://orcid.org/0009-0005-1358-496X
Tobias SeibelMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.ORCID https://orcid.org/0009-0004-9115-3228
Maria MironovaLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID https://orcid.org/0000-0002-9783-097X
Corinna MeeßenMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.
Jan ClusmannMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.
Yazhou ChenMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.ORCID https://orcid.org/0009-0005-9893-645X
Thriveni B RajuMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.ORCID https://orcid.org/0009-0008-9288-9826
Paul-Henry KoopMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.
Juliette E PearceInstitute for Cell and Tumor Biology, RWTH Aachen University, University Hospital Aachen, Aachen, Germany.ORCID https://orcid.org/0000-0001-8155-6534
Ivan G CostaInstitute for Computational Genomics, University Hospital RWTH Aachen, Aachen, Germany.ORCID https://orcid.org/0000-0003-2890-8697
Thomas StiehlUniklinik RWTH Aachen, Institute for Computational Biomedicine & Disease Modeling, RWTH Aachen University, Aachen, Germany.ORCID https://orcid.org/0000-0001-9686-9197
Andreas SchuppertCenter for Computational Life Sciences, RWTH Aachen University, Aachen, Germany.ORCID https://orcid.org/0000-0003-3783-6605
Kai Markus SchneiderMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.
Yaron RotmanLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID https://orcid.org/0000-0002-7549-8216
Carolin V SchneiderMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.ORCID https://orcid.org/0000-0002-6728-9246

Funding

Interdisciplinary Centre for Clinical Research, RWTH Aachen University PTD 1-13/IA 532313
6 · The paper itself

Abstract

BACKGROUND AND

aimsMetabolic dysfunction associated steatotic liver disease (MASLD) is the most prevalent liver disease, yet accurate early detection remains challenging. A particular diagnostic obstacle is distinguishing MASLD from metabolic dysfunction and alcohol-related liver disease (MetALD), currently defined using clinically informed moderate alcohol consumption thresholds without biological validation. This study aimed to identify and externally validate plasma proteomic signatures associated with MASLD and assess whether proteomic profiles support a molecular distinction between MASLD and MetALD as currently defined.

methodsWe analysed plasma proteomic profiles using OLINK data from UK Biobank (UKB) participants with liver MRI. MASLD was defined as MRI-PDFF ≥ 5% and metabolic dysfunction (n = 165), MetALD (n = 46) as MASLD with additional moderate alcohol intake and controls as PDFF < 5% (n = 741).

resultsCompared to controls, participants with MASLD showed 17 upregulated and 3 downregulated proteins after Bonferroni correction (adjusted p < 0.05). Among upregulated proteins, leptin (LEP), fatty acid-binding protein, liver (FABP1) and aminoacylase1 (ACY1) and among downregulated, insulin-like growth factor-binding protein 1 (IGFBP1) were externally validated in an independent cohort (clinicaltrials.gov NCT02520609, n = 47). Individuals with MetALD showed no significant proteomic distinction from MASLD. Although the small MetALD sample size may have limited detection of differences, direct differential expression analysis did not identify statistically significant differences between MASLD and MetALD under the current clinical thresholds.

conclusionsMASLD was associated with a reproducible plasma proteomic signature enriched for proteins involved in lipid metabolism, inflammation and hormonal regulation. We did not identify a clear proteomic distinction between MASLD and MetALD under the current alcohol thresholds. However, this finding should be interpreted considering limited power and potential alcohol-exposure misclassification.

Indexed as

Fatty LiverLiver Diseases, AlcoholicNon-alcoholic Fatty Liver DiseaseAgedBiomarkersCase-Control StudiesDiagnosis, DifferentialFatty Acid-Binding ProteinsFemaleHumansLeptinLiverMagnetic Resonance ImagingMaleMiddle AgedProteomicsBiomarkersFABP1 protein, humanFatty Acid-Binding ProteinsLeptindifferential protein expression analysisMASLDpathway enrichmentproteomicssteatotic liver disease

Identifiers

PMID42809338
PMCPMC13623009

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