hepatic and biliary disorders
Primary Biliary Cholangitis (PBC)
Etiology of Primary Biliary Cholangitis
Primary biliary cholangitis (PBC) is the most common liver disease associated with chronic cholestasis in adults. Most (95%) cases occur in women aged 35 to 70. PBC also clusters in families. A genetic predisposition, perhaps involving the X chromosome, probably contributes. There may be an inherited abnormality of immune regulation. An autoimmune mechanism has been implicated; antibodies to antigens located on the inner mitochondrial membranes occur in>95% of cases. These antimitochondrial antibody (AMA), the serologic hallmarks of PBC, are not cytotoxic and are not involved in bile duct damage. PBC is associated with other autoimmune disorders, such as Systemic Sclerosis , T cells attack the small bile ducts. CD4 and CD8 T lymphocytes directly target biliary epithelial cells. The trigger for the immunologic attack on bile ducts is unknown. Exposure to foreign antigens, such as an infectious (bacterial or viral) or toxic agent, may be the instigating event. These foreign antigens might be structurally similar to endogenous proteins (molecular mimicry); then the subsequent immunologic reaction would be autoimmune and self-perpetuating. Destruction and loss of bile ducts lead to impaired bile formation and secretion (cholestasis). Retained toxic materials such as bile acids then cause further damage, particularly to hepatocytes. Chronic cholestasis thus leads to liver cell inflammation and scarring in the periportal areas. Eventually, hepatic inflammation decreases as Hepatic Fibrosis progresses to AMA -negative PBCis characterized by autoantibodies, such as antinuclear antibodies (ANAs), anti–smooth muscle antibodies, or both and has a clinical course and response to treatment that are similar to those of PBC. However, AMA is absent. 