Primary biliary cholangitis (PBC) is a chronic, cholestatic disease, with a female predominance and a female-to-male ratio of approximately 10:1, that typically follows a slowly progressive, decades-long disease course. The disease is usually asymptomatic at the time of diagnosis and it is not uncommon for a patient to present with cirrhosis. Patients with PBC may also present with extrahepatic manifestations, including pruritus, chronic fatigue, and osteoporosis, while co-existence of other autoimmune diseases, such as autoimmune hepatitis, Hashimoto’s disease, Sjogren’s syndrome, or systemic sclerosis is not uncommon. The exact pathogenesis of PBC remains elusive with a variety of different factors, including genetic, epigenetic, and environmental ones, alongside immune dysregulation leading to a dysfunction of biliary “bicarbonate umbrella”, a protective mechanism by which cholangiocyte-secreted bicarbonate creates an alkaline microenvironment shielding the epithelium from bile acid-induced injury, and increased biliary epithelial cells apoptosis.