Semin Liver Dis
DOI: 10.1055/s-0039-1697617
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

Ana Lleo
1  Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy
2  Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center – IRCCS, Rozzano (MI), Italy
,
Patrick S.C. Leung
3  Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, California
,
Gideon M. Hirschfield
4  Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada
,
Eric M. Gershwin
3  Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, California
› Author Affiliations
Further Information

Publication History

Publication Date:
19 September 2019 (eFirst)

Abstract

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune destruction of small to medium size intrahepatic bile ducts. The etiology of PBC remains unknown and pathogenesis features immune-mediated biliary injury, alongside the consequences of chronic cholestasis. PBC is strongly associated with the loss of immune tolerance against mitochondrial antigens and the subsequent presence of an articulated immunologic response that involves both humoral and cellular responses. Both environmental factors and genetic variants increase PBC susceptibility. Biliary epithelial cells have often been considered a passive target of the immune attack in PBC; however, cholangiocyte dedifferentiation, senescence, stress, and deoxyribonucleic acid damage have been recognized to play an active role in the pathogenesis of PBC. This review highlights and discusses the most relevant pathogenetic mechanisms in PBC, focusing on the key factors that lead to the onset of cholestasis and immune activation.