The challenges of primary biliary cholangitis: What is new and what needs to be done

Benedetta Terziroli Beretta-Piccoli, Giorgina Mieli-Vergani, Diego Vergani, John M. Vierling, David Adams, Gianfranco Alpini, Jesus M. Banales, Ulrich Beuers, Einar Björnsson, Christopher Bowlus, Marco Carbone, Olivier Chazouillères, George Dalekos, Andrea De Gottardi, Kenichi Harada, Gideon Hirschfield, Pietro Invernizzi, David Jones, Edward Krawitt, Antonio LanzavecchiaZhe Xiong Lian, Xiong Ma, Michael Manns, Domenico Mavilio, Eamon MM Quigley, Federica Sallusto, Shinji Shimoda, Mario Strazzabosco, Mark Swain, Atsushi Tanaka, Michael Trauner, Koichi Tsuneyama, Ehud Zigmond, M. Eric Gershwin

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number102328
JournalJournal of Autoimmunity
Volume105
DOIs
Publication statusPublished - Dec 2019

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Terziroli Beretta-Piccoli, B., Mieli-Vergani, G., Vergani, D., Vierling, J. M., Adams, D., Alpini, G., ... Gershwin, M. E. (2019). The challenges of primary biliary cholangitis: What is new and what needs to be done. Journal of Autoimmunity, 105, [102328]. https://doi.org/10.1016/j.jaut.2019.102328