{"doi":"10.1016/j.jcmgh.2022.11.006","title":"Pathophysiological Roles of Ductular Reaction in Liver Inflammation and Hepatic Fibrogenesis","abstract":"See counterpoint on page 806. See counterpoint on page 806. Ductular reaction is referred to as expansion of proliferative and reactive cells that express biliary markers, such as cytokeratin (CK)-7 and CK-19.1Sato K. Marzioni M. Meng F. et al.Ductular reaction in liver diseases: pathological mechanisms and translational significances.Hepatology. 2019; 69: 420-430Crossref PubMed Scopus (209) Google Scholar Ductular reaction is identified by histologic staining in liver specimen of patients with various liver diseases including cholangiopathies, viral hepatitis, and alcoholic and nonalcoholic liver diseases.1Sato K. Marzioni M. Meng F. et al.Ductular reaction in liver diseases: pathological mechanisms and translational significances.Hepatology. 2019; 69: 420-430Crossref PubMed Scopus (209) Google Scholar Ductular reaction is clinically recognized as bile duct hyperplasia; however, the term \"ductular reaction\" is more commonly used in recent studies to define enhanced intrahepatic bile duct mass that can be attributed to the proliferation of cholangiocytes and/or transdifferentiation of various hepatic cells.1Sato K. Marzioni M. Meng F. et al.Ductular reaction in liver diseases: pathological mechanisms and translational significances.Hepatology. 2019; 69: 420-430Crossref PubMed Scopus (209) Google Scholar It is known that ductular reaction is associated with liver fibrosis and thought to be caused by expansion of hepatic progenitor cells (HPCs).2Williams M.J. Clouston A.D. Forbes S.J. Links between hepatic fibrosis, ductular reaction, and progenitor cell expansion.Gastroenterology. 2014; 146: 349-356Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar Accumulating evidence indicates that ductular reaction (ie, expansion of CK-7+ or CK-19+ cells) can be caused not only by HPCs, but also other hepatic cells. Bile duct epithelial cells, cholangiocytes, express CK-7 and CK-19 and proliferate during bile duct injury, which is identified as ductular reaction.1Sato K. Marzioni M. Meng F. et al.Ductular reaction in liver diseases: pathological mechanisms and translational significances.Hepatology. 2019; 69: 420-430Crossref PubMed Scopus (209) Google Scholar Furthermore, in certain pathologic conditions, hepatocytes can transdifferentiate into cholangiocyte-like cells expressing CK-7 or CK-19 to compensate the loss of cholangiocyte numbers and functions.3Nejak-Bowen K. If it looks like a duct and acts like a duct: on the role of reprogrammed hepatocytes in cholangiopathies.Gene Expr. 2020; 20: 19-23Crossref PubMed Scopus (5) Google Scholar Ductular reaction can be induced by expansion of HPCs, cholangiocytes, or hepatocytes, and functional roles of ductular reaction may differ depending on liver diseases or origins of expanding cells. This section discusses the pathophysiological roles of ductular reaction in liver diseases. Hepatic cells communicate with each other to coordinate pathophysiological responses against liver injury via secreting cytokines, chemokines, or extracellular vesicles.4Sato K. Kennedy L. Liangpunsakul S. et al.Intercellular communication between hepatic cells in liver diseases.Int J Mol Sci. 2019; 20: 2180Crossref PubMed Scopus (33) Google Scholar In the portal area and the HPC niche, HPCs, hepatic stellate cells, and macrophages secrete and receive cytokines and growth factors leading to liver inflammation and regeneration.2Williams M.J. Clouston A.D. Forbes S.J. Links between hepatic fibrosis, ductular reaction, and progenitor cell expansion.Gastroenterology. 2014; 146: 349-356Abstract Full Text Full Text PDF PubMed Scopus (229) Google Scholar Ductular reaction is associated with portal inflammation and neutrophil infiltration in alcoholic hepatitis, and the cells in ductular reaction (CK-7+ cells) express elevated neutrophil recruiting chemokines and HPC markers.5Aguilar-Bravo B. Rodrigo-Torres D. Arino S. et al.Ductular reaction cells display an inflammatory profile and recruit neutrophils in alc","journal":"Cellular and Molecular Gastroenterology and Hepatology","year":2022,"id":259286,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":314386,"name":"Linh Pham","orcid":"0000-0002-3696-3963","position":1,"is_corresponding":false},{"id":257784,"name":"Shannon Glaser","orcid":"0000-0002-0749-773X","position":2,"is_corresponding":false},{"id":257785,"name":"Heather Francis","orcid":"0000-0002-3466-3545","position":3,"is_corresponding":false},{"id":257786,"name":"Gianfranco Alpini","orcid":"0000-0002-6658-3021","position":4,"is_corresponding":false},{"id":257775,"name":"Keisaku Sato","orcid":"0000-0001-5380-8001","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:25:47.305414Z","pmid":"36435428","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}