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World J Gastroenterol. Oct 7, 2023; 29(37): 5305-5312
Published online Oct 7, 2023. doi: 10.3748/wjg.v29.i37.5305
Sequence of events leading to primary biliary cholangitis
Ilaria Lenci, Paola Carnì, Martina Milana, Agreta Bicaj, Alessandro Signorello, Leonardo Baiocchi
Ilaria Lenci, Paola Carnì, Martina Milana, Agreta Bicaj, Alessandro Signorello, Leonardo Baiocchi, Hepatology Unit, University of Tor Vergata, Rome 00133, Italy
Paola Carnì, Agreta Bicaj, Leonardo Baiocchi, Postgraduate School in Hepato/Gastroenterology, Catholic University Our Lady of Good Counsel, Tirana 1004, Albania
Author contributions: Lenci I acquisition of data, analysis and interpretation, drafting of manuscript, critical revision; Carnì P, Milana M, Bicaj A, and Signorello A acquisition of data, critical revision; Baiocchi L proposal of study, study conception, correction of manuscript, critical revision.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Leonardo Baiocchi, MD, PhD, Associate Professor, Senior Scientist, Hepatology Unit, University of Tor Vergata, No. 81 Viale Oxford, Rome 00133, Italy. baiocchi@uniroma2.it
Received: July 7, 2023
Peer-review started: July 7, 2023
First decision: August 15, 2023
Revised: August 22, 2023
Accepted: September 11, 2023
Article in press: September 11, 2023
Published online: October 7, 2023
Processing time: 79 Days and 18.4 Hours
Abstract

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that is observed more frequently in middle-aged women. This disorder is considered an autoimmune disease, since liver injury is sustained by the presence of self-directed antimitochondrial antibodies targeting the bile duct cells. The prognosis may vary depending on an early diagnosis and response to therapy. However, nearly a third of patients can progress to liver cirrhosis, thus requiring a liver transplant. Traditional immunosuppressive therapies, commonly employed for other autoimmune diseases, have limited effects on PBC. In fact, dramatic functional changes that occur in the biliary epithelium in the course of inflammation play a major role in perpetuating the injury. In this minireview, after a background on the disease and possible predisposing factors, the sequential cooperation of cellular/molecular events leading to end-stage PBC is discussed in detail. The rise and maintenance of the autoimmune process, as well as the response of the biliary epithelia during inflammatory injury, are key factors in the progression of the disease. The so-called “ductular reaction (DR)”, intended as a reactive expansion of cells with biliary phenotype, is a process frequently observed in PBC and partially understood. However, recent findings suggest a strict relationship between this pathological picture and the progression to liver fibrosis, cell senescence, and loss of biliary ducts. All these issues (onset of chronic inflammation, changes in secretive and proliferative biliary functions, DR, and its relationship with other pathological events) are discussed in this manuscript in an attempt to provide a snapshot, for clinicians and researchers, of the most relevant and sequential contributors to the progression of this human cholestatic disease. We believe that interpreting this disorder as a multistep process may help identify possible therapeutic targets to prevent evolution to severe disease.

Keywords: Primary biliary cholangitis; Cholangiocyte; Biliary secretion; Biliary proliferation; Ductular reaction; Antimitochondrial antibody; Cellular senescence; Liver fibrosis

Core Tip: Primary biliary cholangitis is a chronic cholestatic human disease. The pathological processes that favor the evolution toward end-stage liver disease during this disorder are only partially elucidated. The aim of this minireview is to summarize the sequential pathological contributors, supporting the progression of liver injury, in the course of this disease.