Ductular reaction in liver diseases: pathological mechanisms and translational significances
Open accessAbstract
Ductular reaction (DR) is characterized by the proliferation of reactive bile ducts induced by liver injuries. DR is pathologically recognized as bile duct hyperplasia and is commonly observed in biliary disorders. It can also be identified in various liver disorders including nonalcoholic fatty liver disease. DR is associated with liver fibrosis and damage, and the extent of DR parallels to patient mortality. DR raises scientific interests because it is associated with transdifferentiation of liver cells and may play an important role in hepatic regeneration. The origin of active cells during DR can be cholangiocytes, hepatocytes, or hepatic progenitor cells, and associated signaling pathways could differ depending on the specific liver injury or animal models used in the study. Although further studies are needed to elucidate detailed mechanisms and the functional roles in liver diseases, DR can be a therapeutic target to inhibit liver fibrosis and to promote liver regeneration. This review summarizes previous studies of DR identified in patients and animal models as well as currently understood mechanisms of DR.
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CK7- and CK19-expressing ductular cells are significant promoters of fibrosis and interact with multiple cell types, including HSCs, portal fibroblasts and a wide range of immune cells.
“Cytokeratin (CK)7- and CK19-expressing ductular cells are significant promoters of fibrosis and interact with multiple cell types, including HSCs, portal fibroblasts and a wide range of immune cells.49”
From Understanding the cellular interactome of non-alcoholic fatty liver disease (2022) · cites this paper as [49]
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- Authors
- Sato, K., Marzioni, M., Meng, F., Francis, H., Glaser, S., & Alpini, G.
- Affiliations
- Texas A&M Health Science Center (US)
- Marche Polytechnic University (IT)
- Baylor Scott & White Medical Center - Temple (US)
- Corresponding author
- Alpini, Gianfranco
- Venue
- Hepatology
- Published
- 2018-12-27
- Volume
- 69
- Issue
- 1
- Pages
- 420-430
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC6324973
- OpenAlex
- W2885037168
- Cited by
- 423
- References
- 73
- Citations by year
- 2026: 43 · 2025: 44 · 2024: 64 · 2023: 70 · 2022: 89 · 2021: 47 · 2020: 38 · 2019: 24 · 2018: 4
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-09-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX000574, I01 BX003031, I01 BX001724, I01 BX002192)
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (R21AA025997)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK115184, R01DK058411, R01DK108959, R01DK062975, R01DK107310, R01DK076898, R01DK110035)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- ductular reaction, bile duct hyperplasia, liver fibrosis, liver regeneration, transdifferentiation, cholangiocytes, hepatocytes, hepatic progenitor cells, non-alcoholic fatty liver disease, biliary tract diseases, signaling pathways, therapeutic target
- MeSH terms
- Bile Ducts, Humans, Hyperplasia, Liver Diseases, Hepatocytes, Cell Proliferation, Translational Research, Biomedical
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