Update on primary biliary cirrhosis

Abstract 

Primary biliary cirrhosis is an autoimmune chronic liver disease characterized by progressive bile duct destruction eventually leading to cirrhosis, liver failure, and death. The autoimmune pathogenesis is supported by a plethora of experimental and clinical data, such as the presence of autoreactive T cells and serum autoantibodies. The aetiology remains unknown, although evidence suggests a role for both genetic susceptibility and environmental factors that remain to be determined. In fact, a number of chemicals and infectious agents have been proposed to induce the disease in predisposed individuals. The recent availability of several murine models will significantly help in understanding pathophysiology mechanisms. In this review, we critically summarize the most recent data on the aetiopathogenesis of primary biliary cirrhosis, discuss the latest theories and developments, and suggest directions for future research.

Abbreviations: PBC, primary biliary cirrhosis, AMA, anti-mitochondrial antibodies, IgM, immunoglobulin M, ANA, anti-nuclear antibody, PDC-E2, E2 subunit of pyruvate dehydrogenase, HLA, human leukocyte antigen, XCI, X-chromosome inactivation, dnTGFβRII, dominant negative form of transforming grown factor β receptor II, NOD, non-obese diabetic, Treg, regulatory T cell, NK, natural killer, PAMPs, pathogen-associated molecular patterns, TLRs, toll-like receptors, OADC, 2-oxoacid dehydrogenase, OADC-E2, E2 components of 2-oxo glutarate dehydrogenase, BCOADC-E2, E2 components of branched-chain 2-oxo-acid dehydrogenase, E3BP, E3 binding protein, PDC-E1α, E1α subunit of the pyruvate dehydrogenase complex, IIF, indirect immunofluorescence, ND, nuclear dots, PML, promyelocytic leukaemia proteins, NPC, nuclear pore complex, ACA, anti-centromere antibodies, BEC, biliary epithelial cells

Keywords: Autoantibodies, Autoimmune cholangitis, Tolerance breakdown