What is the first-line treatment for a patient with Primary Biliary Cholangitis (PBC)?

Primary Biliary Cholangitis Treatment

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

First-Line Therapy: UDCA

UDCA represents the cornerstone of PBC management based on multiple placebo-controlled trials demonstrating significant reductions in serum bilirubin, alkaline phosphatase, GGT, cholesterol, and IgM compared to placebo. 2, 3 More importantly, long-term UDCA treatment delays histological progression when initiated early and reduces the likelihood of liver transplantation or death in patients with moderate to severe disease. 2, 3

Dosing and Administration

• Standard dose: 13-15 mg/kg/day 1, 2, 3
• Target: 90% of patients should receive therapy at adequate dose or be documented as intolerant 1
• Critical warning: Never use high-dose UDCA (>20 mg/kg/day) as this has been associated with worse outcomes in cholestatic liver diseases 4, 3
• Timing consideration: UDCA must be given 2-4 hours before or after cholestyramine if both are prescribed, typically giving UDCA at night 1

Baseline Assessment Before Starting Treatment

Before initiating UDCA, perform the following evaluations:

• Abdominal ultrasound to exclude alternative causes of cholestasis (required in 90% of patients) 1, 3
• Confirm absence of decompensated cirrhosis (Child-Pugh B or C) or portal hypertension (ascites, varices, persistent thrombocytopenia) 5
• Document presence/absence of fatigue and pruritus 1, 3
• Osteoporosis risk assessment (should be completed within 5 years in 80% of patients) 1, 3

Response Assessment After 1 Year

After 12 months of UDCA therapy at adequate dosing, perform biochemical response evaluation using validated risk stratification tools:

• Preferred tools: GLOBE or UK-PBC Risk Scores (most accurate) 2, 3
• Documentation standard: 80% of patients should have response status recorded 1, 2
• Purpose: Identify patients at risk of progressive disease who may require second-line therapy 1

Inadequate Response Criteria

Patients not meeting UDCA response criteria after 1 year should be considered for:

• Clinical trials of second-line therapies 1
• Second-line agents including obeticholic acid (if no contraindications), fibrates, or newer PPAR agonists 6, 7

Second-Line Therapy Considerations

Obeticholic Acid (OCA)

Absolute contraindications (per FDA labeling): 5

• Decompensated cirrhosis (Child-Pugh B or C)
• Prior decompensation event
• Compensated cirrhosis with evidence of portal hypertension (ascites, varices, persistent thrombocytopenia)

Dosing if appropriate: 5

• Start 5 mg once daily for 3 months
• Increase to maximum 10 mg once daily if inadequate ALP/bilirubin reduction and tolerating medication
• Major limitation: High propensity to induce or worsen pruritus 6

Alternative Second-Line Options

• Bezafibrate or fenofibrate: Off-label use with biochemical improvements and potential pruritus benefit 2, 6
• Elafibranor and seladelpar: Recently approved PPAR agonists showing biochemical improvements 6, 7
• These agents may be preferred over OCA in patients with existing pruritus 6

Symptom Management

Pruritus Treatment Algorithm

UDCA does not improve pruritus, requiring separate management. 2, 3

First-line: Cholestyramine 4-16 g/day (must be given 2-4 hours apart from UDCA) 1

Second-line: Rifampicin 300-600 mg/day 1

• Start at 150 mg once to twice daily, titrate based on symptoms and LFTs
• Check LFTs in 2-4 weeks due to hepatotoxicity risk 1
• Consider vitamin K supplementation if icteric 1

Third-line options: 1

• Naltrexone 50 mg/day (start at 12.5 mg/day, titrate slowly to avoid withdrawal symptoms)
• Sertraline 100 mg/day (titrate to symptoms)
• Gabapentin (dose titrate as tolerated)

Fatigue Management

No consistently effective treatment exists for PBC-related fatigue. 2 Patients with profound psychological distress associated with fatigue should be referred to appropriate psychological services. 1 Cognitive behavioral therapy may provide benefit based on experience in other chronic conditions. 1

Ongoing Monitoring Requirements

• Regular liver biochemistry to assess treatment response 2, 3
• Annual symptom documentation (fatigue and pruritus in 90% of patients) 1, 3
• Close monitoring in compensated cirrhosis for new evidence of portal hypertension or increases in bilirubin/INR 5
• Transplant referral if bilirubin >50 μmol/L or any evidence of decompensated liver disease 1

Post-Transplant Management

If liver transplantation has been performed for PBC, UDCA should be administered lifelong at 10-15 mg/kg/day to prevent disease recurrence and improve graft survival. 2, 3

Common Pitfalls to Avoid

• Never use UDCA >20 mg/kg/day - associated with adverse outcomes 4, 3
• Never prescribe OCA in decompensated cirrhosis or with portal hypertension - risk of hepatic decompensation and death 5
• Never give cholestyramine simultaneously with UDCA - prevents UDCA absorption 1
• Do not delay second-line therapy in inadequate responders identified at 1 year 1, 6