What is the first-line treatment medication for Primary Biliary Cholangitis (PBC)?

First-Line Treatment for Primary Biliary Cholangitis

Ursodeoxycholic acid (UDCA) at 13-15 mg/kg/day is the first-line treatment for all patients with Primary Biliary Cholangitis (PBC) who do not have decompensated cirrhosis or evidence of portal hypertension. 1, 2, 3

Initial Treatment Approach

UDCA Dosing and Administration

• Start UDCA at 13-15 mg/kg/day immediately upon diagnosis for patients without cirrhosis or with compensated cirrhosis without portal hypertension 1, 2, 3
• UDCA can be taken with or without food 4
• If taking bile acid binding resins (like cholestyramine), separate UDCA by at least 4 hours to avoid interaction 1, 4
• 90% of patients should receive therapy at adequate dose or be documented as intolerant 1, 2

Evidence Supporting UDCA

UDCA is established based on multiple placebo-controlled trials demonstrating that it:

• Significantly decreases serum bilirubin, alkaline phosphatase, GGT, cholesterol, and IgM 2, 5
• Delays histological progression when started early 2, 5
• Reduces likelihood of liver transplantation or death in moderate to severe disease 2, 5

Baseline Assessment Requirements

Before starting treatment, ensure the following evaluations are completed:

• Abdominal ultrasound to exclude alternative causes of cholestasis (90% of patients) 1, 2, 3
• Liver function tests to establish baseline and rule out decompensated cirrhosis 3, 4
• Assessment for portal hypertension (ascites, varices, thrombocytopenia) as UDCA contraindications exist in these patients 3, 4
• Osteoporosis risk assessment (should be done within 5 years in 80% of patients) 1, 2

Monitoring and Response Assessment

Biochemical Response Evaluation at 1 Year

• After 12 months of UDCA therapy, perform biochemical response assessment using validated risk stratification tools (GLOBE or UK-PBC Risk Scores) 2, 3
• Document response status in 80% of patients 1, 2
• Regular monitoring of liver biochemistry is essential 2, 5

Symptom Monitoring

• Evaluate and document presence of fatigue and pruritus annually in 90% of patients 1, 2, 3
• Note that UDCA does not significantly improve pruritus or fatigue 2, 5, 3

Critical Safety Considerations

Absolute Contraindications to UDCA

• Never use high-dose UDCA (>20 mg/kg/day) as this has been associated with worse outcomes in cholestatic liver diseases 5, 3
• Decompensated cirrhosis (Child-Pugh B or C) 4
• Complete biliary obstruction 4

When to Refer or Escalate

• Refer to transplant hepatology if bilirubin exceeds 50 μmol/L or any evidence of decompensated liver disease develops 1, 3
• Patients with inadequate response at 1 year require consideration of second-line therapies 2, 6

Management of Common Symptoms

Pruritus Management (if present)

Since UDCA does not improve pruritus 2, 5, use the following stepwise approach:

• First-line: Cholestyramine (taken separately from UDCA by at least 4 hours) 1
• Second-line: Rifampicin with appropriate monitoring for side effects 1
• Additional options: Naltrexone (start at 12.5 mg/day, titrate slowly), sertraline, or gabapentin 1, 2

Fatigue Management

• No consistently effective pharmacological treatment exists for PBC-related fatigue 2
• Refer patients with profound psychological distress to appropriate psychological services 1
• Consider patient support groups for all patients 1

Post-Transplant Considerations

• If patient has undergone liver transplantation for PBC, continue UDCA lifelong at 10-15 mg/kg/day to prevent disease recurrence 2, 3
• Post-transplant UDCA reduces risk of PBC recurrence and improves graft survival 2, 3

Common Pitfalls to Avoid

• Do not delay UDCA initiation while waiting for additional testing beyond basic cholestasis workup 1, 2
• Do not use UDCA and cholestyramine simultaneously without proper time separation (4+ hours) 1, 4
• Do not wait beyond 12 months to assess response as earlier criteria (Xi'an criterion at 1 month) may identify non-responders sooner 7
• Do not assume UDCA will improve symptoms - it primarily affects biochemical markers and disease progression, not fatigue or pruritus 2, 5, 3