What is the first-line treatment for a patient with 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

All patients with PBC should be offered UDCA therapy at 13-15 mg/kg/day as first-line treatment, with a target of 90% of patients receiving therapy at an adequate dose or being documented as intolerant. 1, 2, 3 This recommendation is based on multiple placebo-controlled trials and long-term case-control studies demonstrating that UDCA:

• Significantly decreases serum bilirubin, alkaline phosphatase, GGT, cholesterol, and IgM levels compared to placebo 2, 3
• Delays histological progression when started at early disease stages 2, 3
• Reduces the likelihood of liver transplantation or death in patients with moderate to severe disease 2, 3

Critical contraindication: Never use high-dose UDCA (>20 mg/kg/day) as this has been associated with worse outcomes in cholestatic liver diseases. 4, 3

Pre-Treatment Assessment

Before initiating UDCA, perform the following baseline evaluations:

• Abdominal ultrasound in 90% of patients to exclude alternative causes of cholestasis 1, 2, 3
• Symptom assessment for fatigue and pruritus, documented in 90% of patients 1, 2
• Osteoporosis risk assessment within 5 years in 80% of patients 1, 2
• Exclude decompensated cirrhosis, prior decompensation events, or evidence of portal hypertension (ascites, gastroesophageal varices, persistent thrombocytopenia), as these are contraindications to treatment 5

Monitoring and Response Assessment

After 1 year of UDCA therapy at 13-15 mg/kg/day, perform biochemical response evaluation using validated risk stratification tools such as the GLOBE or UK-PBC Risk Scores, with documentation in 80% of patients. 1, 2, 3 These tools are the most accurate for identifying patients at risk of progressive disease. 2, 3

Regular monitoring should include:

• Liver biochemistry to assess treatment response 2, 4, 3
• Annual symptom evaluation for fatigue and pruritus in 90% of patients 1, 2
• Bilirubin monitoring: Refer patients with bilirubin >50 μmol/L or evidence of decompensated liver disease to a hepatologist linked to a transplant center 1

Important Limitations and Caveats

UDCA does not significantly improve pruritus or fatigue, which are common symptoms in PBC. 2, 4, 3 These symptoms require separate management strategies:

• For pruritus: First-line therapy is cholestyramine (4-16 g/day), given 2-4 hours before or after UDCA to avoid interaction 1
• Second-line for pruritus: Rifampicin (300-600 mg/day) with regular LFT monitoring 1
• Additional options: Naltrexone, sertraline, or gabapentin for refractory cases 1, 2

Second-Line Therapy Considerations

For patients with inadequate biochemical response after 1 year of UDCA (approximately 40% of patients), second-line therapies should be considered. 6, 7 Options include:

• Obeticholic acid (OCA): FDA-approved second-line agent, starting at 5 mg once daily for 3 months, then increasing to 10 mg once daily if tolerated and inadequate response 5

  • Absolute contraindications: Decompensated cirrhosis (Child-Pugh B or C), prior decompensation event, or compensated cirrhosis with evidence of portal hypertension 5
  • Major limitation: High propensity to induce pruritus 6

• Fibrates (bezafibrate, fenofibrate): May improve biochemistry and potentially improve pruritus symptoms 2, 6, 8

• Newer agents: Elafibranor and seladelpar recently approved as second-line therapies 6, 8

Post-Transplant Management

If a patient has undergone liver transplantation for PBC, UDCA should be administered lifelong at 10-15 mg/kg/day to prevent disease recurrence, improve graft survival, and enhance long-term overall survival. 2, 3

Key Clinical Pitfalls to Avoid

• Never delay UDCA initiation while awaiting liver biopsy in patients with typical presentation (cholestatic LFTs and positive AMA) 1
• Do not use UDCA at inadequate doses (<13 mg/kg/day) as this reduces efficacy 1, 2
• Avoid prescribing OCA to patients with any evidence of portal hypertension or decompensated cirrhosis, as this can lead to hepatic decompensation and failure, sometimes fatal or requiring transplant 5
• Ensure cholestyramine is taken separately from UDCA (2-4 hours apart) to prevent binding and reduced UDCA absorption 1