Evidence map›Paper›PMID 37704824›Full record

ArticleVirchows Archiv : an international journal of pathology2024

Three-dimensional analysis of ductular reactions and their correlation with liver regeneration and fibrosis.

Tadashi Yoshizawa, Jae W Lee, Seung-Mo Hong, DongJun Jung, Michaël Noë, Wojciech Zbijewski, Ashley Kiemen, Pei-Hsun Wu, Denis Wirtz, Ralph H Hruban and 2 more

Abstract read
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In one paragraph

Article in Virchows Archiv : an international journal of pathology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Pathogenesis, Non-Invasive Assessments and Treatment of Hepatic Fibrosis in Autoimmune Liver Diseases.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  3. 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

12 authors.

Tadashi YoshizawaDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jae W LeeDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Seung-Mo HongDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
DongJun JungDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michaël NoëDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Wojciech ZbijewskiDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Ashley KiemenDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Pei-Hsun WuDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Denis WirtzDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ralph H HrubanDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Laura D WoodDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kiyoko OshimaDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. koshima3@jhmi.edu.ORCID http://orcid.org/0000-0002-3357-6247

Funding

TRANS NETWORK PROJECTSU54CA143868 · NCI · JOHNS HOPKINS UNIVERSITY · PI SEARSON, PETER C · 2009 to 2013
$13.7M
NCI NIH HHS U54 CA143868
6 · The paper itself

Abstract

The liver has multiple regeneration modes, including hepatocellular hypertrophy and self-renewal of hepatocytes. When hepatocyte proliferation is impaired, hepatic progenitor cells may proliferate through ductular reaction (DR), differentiate into hepatocytes, and contribute to fibrosis. However, the three-dimensional spatial relationship between DR and regenerating hepatocytes and dynamic changes in DR associated with fibrosis remain poorly understood. Here, we performed three-dimensional (3D) imaging of cleared 42 liver explants with chronic and acute liver diseases and 4 normal livers to visualize DR. In chronic hepatic liver diseases, such as viral hepatitis, steatohepatitis, autoimmune hepatitis, and cryptogenic cirrhosis, the total length and number of branches of DR showed a significant positive correlation. We studied the spatial relationship between DR and GS-expressing cells using glutamine synthetase (GS) and cytokeratin 19 (CK19) as markers of liver regeneration and DR, respectively. The percentage of CK19-positive cells that co-expressed GS was less than 10% in chronic liver diseases. In contrast, nearly one-third of CK19-positive cells co-expressed GS in acute liver diseases, and chronic cholestatic liver diseases, including primary biliary cholangitis and primary sclerosing cholangitis, showed no co-expression. We also found that DR was longer and had more branching in livers with progressive fibrosis compared to those with regressive fibrosis. Our results suggest that DR displays varying degrees of spatial complexity and contribution to liver regeneration. DR may serve as hepatobiliary junctions that maintain continuity between hepatocytes and bile ducts rather than hepatocyte regeneration in chronic liver diseases.

Indexed as

HepatocytesImaging, Three-DimensionalLiver CirrhosisLiver RegenerationBile DuctsGlutamate-Ammonia LigaseHumansKeratin-19LiverLiver DiseasesMaleGlutamate-Ammonia LigaseKeratin-19Ductular reactionGlutamine synthetaseLiverLiver regenerationThree-dimensionTissue clearing

Identifiers

PMID37704824

What OpenQuestion holds

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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.