Genetics and epigenetics in the pathogenesis of primary biliary cholangitis

Primary biliary cholangitis (PBC) is a chronic, slowly progressive cholestatic autoimmune liver disease predominantly afflicting women. PBC is characterized by the presence of disease-specific antimitochondrial antibodies and the histological destruction of intrahepatic bile ducts, which eventually lead to cirrhosis and hepatic failure. Fortunately, ursodeoxycholic acid therapy has improved the outcome of the vast majority of PBC cases. Although the etiology of PBC has not yet been elucidated, human leukocyte antigen (HLA) class II alleles have been consistently associated with disease onset for decades. PBC patients may also have genetically determined risk factors in non-HLA regions. Meanwhile, exposure to environmental factors, such as infectious diseases and harmful chemicals, can produce epigenetic alterations in some individuals and subsequent PBC onset. In this review, we describe the influence of HLA alleles and other gene polymorphisms on PBC along with the results of genome-wide association studies on this disease and its future prospects in terms of epigenetics.