What is the management of primary biliary cholangitis (PBC)?

Management of Primary Biliary Cholangitis (PBC)

All patients with PBC should be offered therapy with ursodeoxycholic acid (UDCA) at a dose of 13-15 mg/kg/day as first-line treatment. 1

Diagnosis and Initial Assessment

• Diagnosis is based on:

  • Cholestatic liver biochemistry
  • Presence of antimitochondrial antibodies (AMAs)
  • Exclusion of other causes of cholestasis

• Initial workup should include:

  • Abdominal ultrasound to exclude alternative etiologies for cholestasis (standard: 90% of patients) 1
  • Assessment for symptoms, particularly fatigue and pruritus 1
  • Risk assessment for osteoporosis 1

Treatment Algorithm

First-Line Therapy

• UDCA at 13-15 mg/kg/day for all patients 1
  • Improves liver biochemistry
  • Delays progression to cirrhosis
  • Improves transplant-free survival

Response Assessment

• Evaluate biochemical response after 12 months of UDCA therapy 1
• Document response status using validated criteria (Paris-I, Paris-II, Toronto, or GLOBE)
• Response assessment should be documented in 80% of patients 1

Second-Line Therapy

For patients with inadequate response to UDCA:

• Obeticholic acid (OCA) - FDA approved for:
  • Patients with inadequate response to UDCA (in combination with UDCA)
  • Patients unable to tolerate UDCA (as monotherapy) 2
  • Contraindicated in decompensated cirrhosis or complete biliary obstruction 2

Special Considerations

Symptom Management

1. Pruritus

   • First-line: Cholestyramine
   • Second-line: Rifampicin or naltrexone 1
   • Monitor liver function with rifampicin due to potential hepatotoxicity

2. Fatigue

   • Exclude alternative causes (anemia, hypothyroidism, sleep disorders)
   • Consider psychological support for profound fatigue-related distress 1

3. Nutritional Support

   • Monitor for fat-soluble vitamin deficiencies (A, D, E, K)
   • Consider empirical vitamin supplementation in advanced disease

Monitoring and Follow-up

• Regular liver biochemistry monitoring
• Assess for disease progression and development of complications
• Risk stratification for progressive disease based on biochemical response
• Recent evidence suggests that achieving normal ALP levels (not just below 1.5×ULN) may provide additional survival benefit, particularly in patients with advanced fibrosis and/or younger age 3

Complications Management

1. Osteoporosis

   • Risk assessment for all patients (standard: 80% within 5 years) 1
   • Treatment according to national guidelines

2. Portal Hypertension

   • Endoscopic screening for varices in patients with cirrhosis
   • Standard management of portal hypertension complications

3. Liver Transplantation

   • Consider for patients with:
     • Bilirubin >50 μmol/L
     • Evidence of decompensated liver disease
     • Discussion with transplant center required

Patient Support

• Offer patients the opportunity to seek support from patient support groups 1
• Consider psychological services referral for patients with significant psychological distress 1

Pitfalls and Caveats

1. Do not use UDCA for prevention of colorectal cancer or cholangiocarcinoma
2. Corticosteroids and immunosuppressants are not indicated for classic PBC but may be considered in overlap syndromes with autoimmune hepatitis
3. Be vigilant for symptoms of disease progression in patients taking obeticholic acid, particularly those with cirrhosis
4. Monitor HDL-C levels in patients on obeticholic acid as it can lower HDL-C levels 2
5. When prescribing bile acid binding resins (cholestyramine), administer at least 4 hours before or after other medications 2

Emerging Therapies

While UDCA and obeticholic acid are the current approved treatments, several other therapies are being investigated:

• Fibrates (off-label, particularly for patients with pruritus) 4
• Novel therapies in clinical trials including FXR agonists, PPAR agonists, and other agents 4