Pathogenesis of primary biliary cholangitis

The initial requirement is a genetically susceptible host, which may involve an inability to suppress an immunologically mediated attack on bile duct cells once it has begun. Some triggering event is required to set this process in motion; it could be any event that damages bile duct cells and exposes the unique primary biliary cholangitis bile duct cell antigen to the cellular or humoral immune system. Progressive damage to bile duct cells causes cholestasis. This sets up a vicious cycle in which retention of toxic substances, such as bile acids, cause chemical damage to hepatocytes. Cholestasis also causes increased expression of HLA Class I and II antigens on bile duct cells and hepatocytes which make them better targets for activated lymphocytes. The gradual loss of bile ducts causes progressive scarring, cirrhosis, portal hypertension, and eventually, liver failure.