TY - JOUR
T1 - The challenges of primary biliary cholangitis
T2 - What is new and what needs to be done
AU - Terziroli Beretta-Piccoli, Benedetta
AU - Mieli-Vergani, Giorgina
AU - Vergani, Diego
AU - Vierling, John M.
AU - Adams, David
AU - Alpini, Gianfranco
AU - Banales, Jesus M.
AU - Beuers, Ulrich
AU - Björnsson, Einar
AU - Bowlus, Christopher
AU - Carbone, Marco
AU - Chazouillères, Olivier
AU - Dalekos, George
AU - De Gottardi, Andrea
AU - Harada, Kenichi
AU - Hirschfield, Gideon
AU - Invernizzi, Pietro
AU - Jones, David
AU - Krawitt, Edward
AU - Lanzavecchia, Antonio
AU - Lian, Zhe Xiong
AU - Ma, Xiong
AU - Manns, Michael
AU - Mavilio, Domenico
AU - Quigley, Eamonn Martin
AU - Sallusto, Federica
AU - Shimoda, Shinji
AU - Strazzabosco, Mario
AU - Swain, Mark
AU - Tanaka, Atsushi
AU - Trauner, Michael
AU - Tsuneyama, Koichi
AU - Zigmond, Ehud
AU - Gershwin, M. Eric
N1 - Copyright © 2019 Elsevier Ltd. All rights reserved.
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
KW - Bile acids
KW - Biliary epithelial cells
KW - Biomarkers
KW - Histology
KW - Personalized medicine
KW - Primary biliary cholangitis
UR - http://www.scopus.com/inward/record.url?scp=85072516811&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072516811&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2019.102328
DO - 10.1016/j.jaut.2019.102328
M3 - Review article
C2 - 31548157
AN - SCOPUS:85072516811
SN - 0896-8411
VL - 105
SP - 102328
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
M1 - 102328
ER -