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Time: December 27, 2022

Although the clinical management of primary biliary cholangitis (PBC) has been significantly improved in the last two decades, the current understanding of this multifactorial disease leaves several important nuances to be appreciated. PBC is classically regarded as an autoimmune disease resulting from an attack aimed at the cholangiocytes lining the small intrahepatic bile ducts. This autoimmune attack is triggered by a combinatorial interaction of genetic, epigenetic and environmental factors that leads to tolerance breakdown. Furthermore, microbiota alterations induced by bile acids have a profound impact on the immune cell responses, which are instrumental in the pathogenesis of the disease. Accumulating evidence indicates that not only do different clinical phenotypes exist between sexes but also deep racial diversities and disparities exist that influence outcomes. The clinical course of patients with PBC may be complicated by the unexpected development of primary liver cancer, not only hepatocellular carcinoma but also cholangiocarcinoma. Ursodeoxycholic acid and other second-line treatments can substantially alter the natural history of the disease, but their efficacy remains limited in patients with advanced disease. Starting from these considerations, in this Special Issue, we aim to shed light on these unresolved questions regarding a yet enigmatic disease.

Major Research Topics of this Special issue are as follows:

1. Genetics, epigenetics and environmental triggers in PBC pathogenesis
2. Immunobiology, microbiota and bile acids: translational perspectives in PBC
3. Molecular mechanisms of early biliary damage in PBC
4. Gender and racial differences in PBC phenotypes
5. Malignancy risk of PBC
6. Treatment options and flowchart for PBC