What is the initial treatment for Primary Biliary Cholangitis (PBC)?

Initial Treatment for Primary Biliary Cholangitis (PBC)

Ursodeoxycholic acid (UDCA) at a dose of 13-15 mg/kg/day is the recommended first-line therapy for all patients with Primary Biliary Cholangitis. 1, 2

First-Line Treatment

• UDCA should be offered to all patients with PBC at a dose of 13-15 mg/kg/day, typically divided into two doses 1
• UDCA has been demonstrated to markedly decrease serum bilirubin, alkaline phosphatase, gamma-glutamyl transferase, cholesterol, and immunoglobulin M levels 1
• Long-term treatment with UDCA delays histological progression of the disease when started at an early stage 1
• UDCA should be continued lifelong in patients with PBC to prevent disease progression 1
• The British Society of Gastroenterology recommends that at least 90% of PBC patients should receive UDCA therapy at adequate dose or be documented to be intolerant 1

Monitoring Response to Treatment

• Biochemical response to UDCA should be assessed after 1 year of therapy 1, 2
• Individualized risk stratification using biochemical response indices should be performed to identify patients at risk of progressive disease 1
• The goal of therapy should be normalization of alkaline phosphatase and bilirubin below 0.6 times the upper limit of normal 3
• Patients should be routinely monitored during treatment for biochemical response, tolerability, and progression of PBC 4

Second-Line Treatment for UDCA Non-Responders

• Patients with inadequate response to UDCA after 12 months of treatment are at high risk of progressive disease and need second-line treatment 3
• Obeticholic acid is FDA-approved as second-line therapy for patients with inadequate response to UDCA or who are intolerant to UDCA 4, 5
• Fibrates (bezafibrate, fenofibrate) have shown benefit in improving liver biochemistries in UDCA non-responders, though they are often used off-label 1, 6, 7
• Recently, additional PPAR agonists (elafibranor, seladelpar) have been approved for use in PBC patients with inadequate response to UDCA 5

Special Considerations

• UDCA is safe to continue during pregnancy and breastfeeding in women with PBC 1
• Obeticholic acid should be discontinued during pregnancy and breastfeeding due to lack of safety data 1
• Fibrates may be used after the first trimester of pregnancy if the clinical team believes the benefits outweigh the risks 1
• Patients with PBC should be evaluated for symptoms, particularly fatigue and pruritus, which may require specific management 1
• Risk assessment for osteoporosis should be performed in all PBC patients 1

Management of Symptoms

• For pruritus, first-line treatment is cholestyramine (4-16 g/day), which must be given 2-4 hours before or after UDCA 1
• Second-line treatment for pruritus is rifampicin (300-600 mg/day), with monitoring for hepatotoxicity 1
• Patients with profound psychological distress associated with fatigue should be referred to appropriate psychological services 1
• All patients should be offered the chance to seek support from patient support groups 1

By following this treatment algorithm, patients with PBC can receive optimal care to reduce disease progression, manage symptoms, and improve quality of life.