Liver injury in PBC is progressive and focused initially on the intra-hepatic bile ducts.
Injury to the ducts is typically accompanied by an immune cell infiltration into the portal tracts. Bile duct epithelial cell injury, typically through apoptosis, is initially compensated for by a homeostatic response in which the injured cells proliferate in an attempt to renew the bile ducts. Failure or exhaustion of this compensatory response, with senescence of the proliferated bile duct cells, results in progressive duct loss and cholestasis. Retention of toxic hydrophobic bile acids causes further bile duct epithelial cell injury and a worsening cycle of ductopenia.
Chronic injury to the liver form a combination of the direct primary process and the secondary cholestatic process triggers fibrosis which is progresses to cirrhosis (albeit at a rate which varies significantly between different patients).