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. PBC is frequently associated with other autoimmune conditions and primarily affects middle-aged women. In the early stages, PBC is typically asymptomatic. Fatigue is the most common initial symptom. 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 alkaline phosphatase (ALP) levels, antimitochondrial antibodies (AMA), and liver biopsy findings can establish the diagnosis. Management involves supportive care, e.g., management of cholestasis-associated pruritus, and slowing disease progression with ursodeoxycholic acid. Liver transplantation is the only definitive treatment.
- PBC is considered an autoimmune disease and is thought to be triggered by environmental factors in individuals with a genetic predisposition. 
- Positive family history is a predisposing factor.
- Often associated with other autoimmune conditions, e.g.: 
- 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) 
Patients with PBC are usually initially asymptomatic. 
- Fatigue: most common and often the first symptom
- Marked pruritus: generalized or localized, typically worse at night 
- Symptoms of cholestasis
- Signs of cirrhosis and portal hypertension
- Hyperpigmentation 
- Xanthomas and xanthelasma 
- May be accompanied by clinical features of any associated autoimmune diseases (e.g., sclerodactyly in scleroderma, xerophthalmia in sicca syndrome)
- Suspect PBC in patients with chronic cholestasis.
- Obtain laboratory studies for all patients.
- Consider liver biopsy if the diagnosis remains unclear.
- Diagnosis is confirmed if ≥ 2 of the following are present: 
- Imaging can help exclude alternative diagnoses.
- Liver chemistries: cholestatic pattern of injury
- Liver synthetic function tests: ↓ albumin, ↑ INR in patients with advanced disease
- CBC: thrombocytopenia, e.g., in patients with hypersplenism due to portal hypertension or concomitant ITP 
- Lipid panel: hypercholesterolemia
- PBC-specific autoantibodies
- Immunoglobulins (nonspecific)
Liver biopsy 
- Most patients do not require a liver biopsy to confirm PBC.
- Obtain in certain patients to either:
- Supportive findings
Imaging is not routinely indicated but may be used to exclude alternative diagnoses and/or evaluate for complications. See also “Diagnostics” in “Jaundice and cholestasis.”
- (See “ for details.)
- Biliary obstruction (malignant or benign)
- Drug-induced liver disease
- See also “Common cholestatic causes of conjugated hyperbilirubinemia.”
The differential diagnoses listed here are not exhaustive.
- Start pharmacotherapy with ursodeoxycholic acid for all patients.
- Offer supportive care, including .
- Screen for complications and comorbidities.
- Patients with PBC-AIH overlap should receive simultaneous treatment of AIH (i.e., immunosuppression). 
- Liver transplantation is necessary if liver cirrhosis is advanced.
Liver transplantation is the only definitive treatment, although most cases of PBC can be managed effectively with pharmacotherapy.
- First-line: ursodeoxycholic acid (UDCA, ) : a hydrophilic, nontoxic bile acid with immunomodulatory, anti-inflammatory, choleretic, and cytoprotective effects ; 
Obeticholic acid (OCA): an agonist of the farnesoid X receptor, which is a nuclear receptor that inhibits bile acid synthesis and intake
- Consider in addition to UDCA if there is an inadequate response after 1 year of treatment. 
- Consider as monotherapy in patients with sensitivity or intolerance to UDCA.
- Contraindicated in patients with advanced cirrhosis, i.e., a history of decompensation or signs of decompensated cirrhosis or portal hypertension. 
- Fibrates, e.g., fenofibrate (off-label): may be considered for patients without decompensated cirrhosis and inadequate response to UDCA 
- Obeticholic acid (OCA): an agonist of the farnesoid X receptor, which is a nuclear receptor that inhibits bile acid synthesis and intake
Supportive care 
- Treatment of in patients with
- Prevention of complications
Monitoring and screening 
- Monitoring for disease progression
- Screening for complications of cholestasis
- Screening for complications of cirrhosis
- Measure TSH annually.
- Regularly assess for signs and symptoms of commonly associated autoimmune diseases (see “Etiology”).