Ductular reactions in human liver: Diversity at the interface
Open accessAbstract
Interest in hepatic ductular reactions (DRs) has risen in recent years because of a greater appreciation of their potential roles in regeneration, fibrogenesis, and carcinogenesis. However, confusion exists because there is significant, but often unappreciated diversity at the tissue, cellular, and subcellular levels in DRs of different diseases and stages of disease. DRs are encountered in virtually all liver disorders in which there is organ-wide liver damage and cell loss, but are also present in focal lesions such as focal nodular hyperplasia and adenoma. Moreover, diverse DR phenotypes can be present within any single disease entity, and are shaped by the etiology and evolution of the disease. Although much remains to be clarified, recent studies suggest that the diversity of appearances of the DRs are likely to reflect the differing signals at the anatomic, cellular, and molecular levels driving the proliferative response. These appear to determine the relative proportions of transit-amplifying cells, the degree of hepatocytic or cholangiocytic differentiation, and their relationships with stromal, vascular, and inflammatory components. The molecular signaling pathways governing these regenerative fate decisions closely replicate those found in human and other vertebrate embryos and more generally in stem cell niches throughout the body. Like the latter, complex interactions with matrix as well as mesenchymal and inflammatory cells, vessels, and innervation are likely to be of fundamental importance. Embracing systems/tissue biological approaches to exploring DRs, in addition to more traditional cellular and molecular biological techniques, will further enhance our understanding and, thereby, we believe potentiate new therapeutic possibilities. (Hepatology 2011)
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In human disease, cells analogous to the murine HPCs arise in response to biological or chemical damage, not typically genetic alteration.
“In human disease, cells analogous to the murine HPCs arise in response to biological or chemical damage24, 35 (not typically genetic alteration),”
From Hepatic progenitor cells of biliary origin with liver repopulation capacity (2015) · cites this paper as [24]
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- GOUW, CLOUSTON, AND THEISE 1863 15273350, 2011, 5, Downloaded from https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.24613, Wiley Online Library on [11/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
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- Authors
- Gouw, A. S. H., Clouston, A. D., & Theise, N. D.
- Affiliations
- University Medical Center Groningen (NL)
- The University of Queensland (AU)
- Mount Sinai Beth Israel (US)
- Corresponding author
- Theise, Neil D.
- Venue
- Hepatology
- Published
- 2011-11
- Volume
- 54
- Issue
- 5
- Pages
- 1853-1863
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W1985932431
- Cited by
- 275
- References
- 5
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 20 · 2023: 20 · 2022: 11 · 2021: 14 · 2020: 17 · 2019: 21 · 2018: 30 · 2017: 22 · 2016: 28 · 2015: 22 · 2014: 21 · 2013: 15 · 2012: 13
- FWCI
- 9.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- ductular reaction, liver regeneration, hepatic fibrogenesis, hepatocarcinogenesis, focal nodular hyperplasia, hepatocellular adenoma, transit amplifying cells, inflammatory cells, stem cell niche
- MeSH terms
- Bile Ducts, Intrahepatic, Humans, Liver Diseases, Genetic Variation, Immunophenotyping, Hepatocytes
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