1Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
2European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, 20900 Monza, Italy.
3Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy.
4Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, 20089 Rozzano, Italy.
Primary Biliary Cholangitis (PBC) is a rare autoimmune disease of the liver, affecting mostly females. There is evidence that epigenetic changes have a pathogenic role in PBC. Epigenetic modifications are related to methylation of CpG DNA islands, post-translational modifications of histone proteins, and non-coding RNAs. In PBC, there are data showing a dysregulation of all these levels, especially in immune cells. In addition, epigenetics seems to be involved in complex phenomena such as X monosomy or abnormalities in the process of X chromosome inactivation, which have been reported in PBC and appear to influence its sex imbalance and pathogenesis. We review here historical data on epigenetic modifications in PBC, present new data, and discuss possible links among X-chromosome abnormalities at a genetic and epigenetic level, PBC pathogenesis, and PBC sex imbalance.