Primary biliary cholangitis (PBC; also known as primary biliary cirrhosis) is a chronic progressive liver disease of autoimmune origin that is characterized by destruction of the intralobular bile ducts. The pathogenesis of PBC is unclear; however, it primarily affects middle-aged women and is frequently associated with other autoimmune conditions. In the early stages, PBC is typically asymptomatic. Fatigue is the most common initial complaint. In advanced disease, increased fibrotic changes lead to typical signs of cholestasis (e.g., jaundice), portal hypertension (e.g., ascites, gastrointestinal bleeding), and severe hypercholesterolemia (e.g., xanthomas, xanthelasmas). Elevated cholestasis parameters (ALP, γ-GT, bilirubin) in addition to antimitochondrial antibodies (AMAs) help establish the diagnosis. Management consists of slowing disease progression with ursodeoxycholic acid and relieving symptoms. Liver transplantation is the only definitive treatment.
- The exact cause of PBC is still unclear; however, it is considered as an autoimmune disease.
- Associated with other autoimmune conditions (see “Clinical features” below)
- Positive family history is a predisposing factor.
- 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) 
- Fatigue (usually the first symptom)
- Marked generalized pruritus
- Hyperpigmentation 
- Hepatomegaly, dull lower margin, RUQ discomfort
- Pale stool, dark urine
- Maldigestion (may involve manifestations of deficiency of fat-soluble vitamins; e.g., osteoporosis) 
- Xanthomas and xanthelasma 
- Frequently associated with other autoimmune conditions 
- Laboratory tests
- Performed in case of suspicion for an overlap syndrome or uncertain diagnosis (e.g., if AMA are negative but clinical suspicion is strong)
- Necessary for staging
- (See “ .)
- Biliary obstruction (malignant or benign)
- Drug-induced liver damage
The differential diagnoses listed here are not exhaustive.
There is no cure for PBC. Treatment consists of slowing disease progression and alleviating symptoms. Liver transplantation is the only definitive treatment.
First-line medical therapy: ursodeoxycholic acid (also known as , or UDCA)
- Slows progression of the disease and improves clinical symptoms
- Delays the need for transplantation
- Active ingredient is a hydrophilic bile acid
- Second-line medical therapy: obeticholic acid (agonist of the farnesoid X receptor, a nuclear receptor that inhibits synthesis of cholesterol by promoting the transport of bile acids out of the hepatocytes)
- Liver transplantation necessary if liver cirrhosis is advanced