Etiology
- PBC is considered an autoimmune disease
- Often associated with other autoimmune conditions, e.g.:
- CREST syndrome
- Sicca syndrome
- Autoimmune thyroid disease, especially Hashimoto thyroiditis
- Celiac disease
- Rheumatoid arthritis
Pathophysiology
Inflammation and progressive destruction (likely due to an autoimmune reaction) of the small and medium-sized intrahepatic bile ducts (progressive ductopenia) → defective bile duct regeneration → chronic cholestasis → secondary hepatocyte damage due to increased concentration of toxins that typically get excreted via bile → gradual portal and periportal fibrotic changes → liver failure → liver cirrhosis and portal hypertension (in advanced stage)
Diagnostics
- Liver chemistries: cholestatic pattern of injury
- ↑ ALP, ↑ GGT, ↑ direct bilirubin
- Mild transaminitis (or normal AST and ALT)
Treatment
General principles
- Start pharmacotherapy with ursodeoxycholic acid for all patients.
- Offer supportive care, including management of cholestasis-associated pruritus.
- Liver transplantation is necessary if liver cirrhosis is advanced.
Pharmacotherapy
- First-line: ursodeoxycholic acid (UDCA, ursodiol): a hydrophilic, nontoxic bile acid with immunomodulatory, anti-inflammatory, choleretic, and cytoprotective effects
- Slows disease progression and development of complications (e.g., esophageal varices)
- Prolongs transplant-free and overall survival
- Also used in primary sclerosing cholangitis, cholestasis of pregnancy, and small cholesterol stones