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The challenges of primary biliary cholangitis: What is new and what needs to be done
Open accessAbstract
Primary Biliary Cholangitis (PBC) is an uncommon, chronic, cholangiopathy of autoimmune origin and unknown etiology characterized by positive anti-mitochondrial autoantibodies (AMA), female preponderance and progression to cirrhosis if left untreated. The diagnosis is based on AMA- or PBC-specific anti-nuclear antibody (ANA)-positivity in the presence of a cholestatic biochemical profile, histologic confirmation being mandatory only in seronegative cases. First-line treatment is ursodeoxycholic acid (UDCA), which is effective in preventing disease progression in about two thirds of the patients. The only approved second-line treatment is obeticholic acid. This article summarizes the most relevant conclusions of a meeting held in Lugano, Switzerland, from September 23rd-25th 2018, gathering basic and clinical scientists with various background from around the world to discuss the latest advances in PBC research. The meeting was dedicated to Ian Mackay, pioneer in the field of autoimmune liver diseases. The role of liver histology needs to be reconsidered: liver pathology consistent with PBC in AMA-positive individuals without biochemical cholestasis is increasingly reported, raising the question as to whether biochemical cholestasis is a reliable disease marker for both clinical practice and trials. The urgent need for new biomarkers, including more accurate markers of cholestasis, was also widely discussed during the meeting. Moreover, new insights in interactions of bile acids with biliary epithelia in PBC provide solid evidence of a role for impaired epithelial protection against potentially toxic hydrophobic bile acids, raising the fundamental question as to whether this bile acid-induced epithelial damage is the cause or the consequence of the autoimmune attack to the biliary epithelium. Strategies are needed to identify difficult-to-treat patients at an early disease stage, when new therapeutic approaches targeting immunologic pathways, in addition to bile acid-based therapies, may be effective. In conclusion, using interdisciplinary approaches, groundbreaking advances can be expected before long in respect to our understanding of the etiopathogenesis of PBC, with the ultimate aim of improving its treatment.
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Background
Metadata
- Authors
- Terziroli Beretta-Piccoli, B., Mieli-Vergani, G., Vergani, D., Vierling, J. M., Adams, D., Alpini, G., Banales, J. M., Beuers, U., Björnsson, E., Bowlus, C., Carbone, M., Chazouillères, O., Dalekos, G., De Gottardi, A., Harada, K., Hirschfield, G., Invernizzi, P., Jones, D., Krawitt, E., Lanzavecchia, A., Lian, Z.-X., Ma, X., Manns, M., Mavilio, D., Quigley, E. M., Sallusto, F., Shimoda, S., Strazzabosco, M., Swain, M., Tanaka, A., Trauner, M., Tsuneyama, K., Zigmond, E., & Gershwin, M. E.
- Affiliations
- King's College Hospital (GB)
- Baylor College of Medicine (US)
- NIHR Birmingham Biomedical Research Centre (GB)
- Richard L. Roudebush VA Medical Center (US)
- Amsterdam UMC Location University of Amsterdam (NL)
- University of California, Davis (US)
- University of Milan (IT)
- Hôpital Saint-Antoine (FR)
- University of Thessaly (GR)
- Kanazawa University (JP)
- University Health Network (CA)
- NIHR Newcastle Biomedical Research Centre (GB)
- University of Vermont (US)
- Institute for Research in Biomedicine (CH)
- South China University of Technology (CN)
- Shanghai Jiao Tong University (CN)
- Medizinische Hochschule Hannover (DE)
- Houston Methodist (US)
- Kyushu University (JP)
- Yale University (US)
- University of Calgary (CA)
- Teikyo University (JP)
- Medical University of Vienna (AT)
- Tokushima University (JP)
- Tel Aviv University (IL)
- ORCID
- Vergani, Diego
- Vierling, John M.
- Adams, David
- Alpini, Gianfranco
- Beuers, Ulrich
- Bowlus, Christopher
- Carbone, Marco
- Chazouillères, Olivier
- Dalekos, George
- Harada, Kenichi
- Hirschfield, Gideon
- Invernizzi, Pietro
- Jones, David
- Lanzavecchia, Antonio
- Lian, Zhe-Xiong
- Ma, Xiong
- Manns, Michael
- Mavilio, Domenico
- Sallusto, Federica
- Shimoda, Shinji
- Strazzabosco, Mario
- Swain, Mark
- Tanaka, Atsushi
- Trauner, Michael
- Tsuneyama, Koichi
- Zigmond, Ehud
- Gershwin, M. Eric
- Venue
- Journal of Autoimmunity
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 105
- Pages
- 102328
- ISSN
- 0896-8411 (ISSN-L)
- OpenAlex
- W2974241762
- Cited by
- 114
- References
- 318
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 13 · 2023: 18 · 2022: 26 · 2021: 21 · 2020: 18 · 2019: 3
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Journal of Autoimmunity (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- University of Thessaly Institutional Repository (University of Thessaly) (submittedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by-nc-nd)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NIHR200243, NF-SI-0513-10091)
- Medical Research Council (MR/L001489/1)
- Japan Society for the Promotion of Science (18K07069, 17H04058)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- primary biliary cirrhosis, antimitochondrial antibodies, antinuclear antibodies, ursodeoxycholic acid, obeticholic acid, liver histopathology, bile acids, biliary epithelium, autoimmune liver disease, disease progression, difficult-to-treat patients, etiopathogenesis
- MeSH terms
- Antibodies, Antinuclear, Autoimmune Diseases, Chenodeoxycholic Acid, Cholagogues and Choleretics, Congresses as Topic, Female, Humans, Liver, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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