Primary Biliary Cholangitis

Primary Biliary Cholangitis is a chronic progressive autoimmune liver disease characterized by destruction of intrahepatic bile ducts. The pathophysiology involves loss of tolerance to self-antigens on mitochondrial proteins (particularly PDC-E2, a component of the pyruvate dehydrogenase complex), leading to autoimmune attack primarily on small to medium-sized bile ducts. This triggers both innate and adaptive immune responses including autoreactive T cells and B cells producing antimitochondrial antibodies (AMA). Progressive bile duct destruction leads to cholestasis (impaired bile flow) and subsequent liver inflammation, fibrosis, and eventual cirrhosis if the disease progresses unchecked. PBC typically presents insidiously with fatigue and pruritus as early symptoms. Many patients are asymptomatic at diagnosis, discovered through abnormal liver function tests on routine screening. Cholestasis markers (alkaline phosphatase, gamma-glutamyl transferase) are characteristically elevated. Antimitochondrial antibody (AMA) positivity is virtually diagnostic, present in 90-95% of patients. Progressive disease leads to portal hypertension, ascites, hepatic encephalopathy, and eventual liver failure. Ursodeoxycholic acid (UDCA), the standard first-line therapy, slows but does not halt disease progression in all patients. Approximately 25-30% of patients show inadequate biochemical response to UDCA. Bone disease (osteoporosis) is common due to cholestasis-induced malabsorption of vitamin D and increased bone turnover.