Evidence map›Paper›PMID 40560681›Full record

ArticleHepatology (Baltimore, Md.)2026

Multimodal transcriptomics identifies metallothionein as a novel pathway in primary sclerosing cholangitis.

Brian K Chung, Markus S Jördens, Jonas Øgaard, Henrik Mikael Reims, Benedicte Flateland, Tom Luedde, Xiaojun Jiang, Tom H Karlsen, Espen Melum

Abstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

9 authors.

Brian K ChungNorwegian PSC Research Center, Division of Surgery and Specialized Medicine, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.ORCID 0000-0002-9523-7515
Markus S JördensNorwegian PSC Research Center, Division of Surgery and Specialized Medicine, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.ORCID 0000-0002-0544-1118
Jonas ØgaardNorwegian PSC Research Center, Division of Surgery and Specialized Medicine, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.ORCID 0000-0001-9194-5939
Henrik Mikael ReimsDepartment of Pathology, Oslo University Hospital Rikshospitalet, Oslo, Norway.ORCID 0000-0002-2018-7787
Benedicte FlatelandNorwegian PSC Research Center, Division of Surgery and Specialized Medicine, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Tom LueddeDepartment of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University Düsseldorf, University Hospital Düsseldorf, Düsseldorf, Germany.ORCID 0000-0002-6288-8821
Xiaojun JiangNorwegian PSC Research Center, Division of Surgery and Specialized Medicine, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.ORCID 0000-0003-1503-5997
Tom H KarlsenNorwegian PSC Research Center, Division of Surgery and Specialized Medicine, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.ORCID 0000-0002-8289-9931
Espen MelumNorwegian PSC Research Center, Division of Surgery and Specialized Medicine, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.ORCID 0000-0001-6903-6878

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsPrimary sclerosing cholangitis (PSC) is a chronic inflammatory bile duct disorder of unknown etiology characterized by uneven peribiliary infiltration and liver fibrosis. To localize potential disease pathways to specific microanatomical liver regions, we combined spatial and single-nuclei transcriptomics (snRNA-seq) to analyze biopsies from a spectrum of PSC and disease control explants. APPROACH AND

resultsLiver specimens from 23 PSC (transplant indications: 4 recurrent cholangitis, 7 dysplasia, 12 cirrhosis) and 7 disease controls with cirrhosis (4 metabolic dysfunction-associated steatohepatitis, MASH; 3 alcohol-associated liver disease, ALD) were analyzed by spatial transcriptomics (76,664 spots) and 16 of the same explants were also assessed by snRNA-seq (12 PSC, 2 MASH, 2 ALD; 91,891 nuclei). PSC livers expressed a robust signature of metallothionein ( MT1E, MT1G , MT1H ) and acute inflammation markers ( SAA1 , SAA2 ) at the parenchyma-fibrosis interface compared to disease controls. SnRNA-seq showed that the strongest metallothionein signal originated from a subtype of APOE + hepatocytes that, by spatial transcriptomics and immunohistochemistry, were consistently localized to the edge of fibrotic lesions in PSC explants. Biliary inflammation induced by 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding in mice resulted in significant Mt1 liver expression and liver MT1G expression correlated with AST, ALT, ALP, and bilirubin levels at the time of liver transplantation.

conclusionsCombinatorial spatial and high-resolution single-nuclei transcriptomics on the largest number of PSC liver explants to date revealed metallothionein as a novel PSC pathway that could be interrogated in future studies aiming to develop effective therapeutic interventions for PSC.

Indexed as

Cholangitis, SclerosingMetallothioneinTranscriptomeAdultAnimalsFemaleGene Expression ProfilingHumansLiverLiver CirrhosisMaleMiceMiddle AgedMetallothioneinlivermetallothioneinprimary sclerosing cholangitissingle-nuclei RNA sequencingspatial transcriptomics

Identifiers

PMID40560681
PMCPMC13089832

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.