Primary biliary cholangitis: Its science and practice

Abstract

Primary biliary cholangitis (PBC) is an autoimmune liver disorder characterized by progressive destruction of intrahepatic bile ducts, leading to cholestasis, cirrhosis, and liver failure. The etiology of PBC is unknown; however a complex interaction between genetic, environmental, and autoimmune factors is believed to play a role. The major hallmark of PBC is the presence of antimitochondrial antibodies (AMA), with sensitivity and specificity for PBC >90-95%. The immunodominant epitopes recognized by AMA are all mapped within the lipoyl domains of the E2 subunits of the pyruvate dehydrogenase complex (PDC-E2). In addition to autoantibodies, PBC is characterized by an enrichment of autoreactive CD4+ and CD8+ T cells, by enhanced natural killer (NK) cell activity and monocyte responses and accumulation of Th17 cells around damaged bile ducts. Controversial findings regarding numbers and function of regulatory T cells have been reported. The development of several animal models has aided the study and understanding of different aspects of PBC pathogenesis; however no "perfect model" has been developed to date. Novel therapeutic avenues targeting bile acids, nuclear receptors, immune cell receptors, and cytokines have been developed with promising results.