What is the first-line treatment 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 who do not have decompensated cirrhosis or evidence of portal hypertension. 1, 2, 3

Treatment Initiation and Dosing

• All patients with PBC should be offered UDCA therapy at 13-15 mg/kg/day as initial treatment, with a goal of 90% of patients receiving an adequate dose or being documented as intolerant 1, 2
• This dosing is established based on multiple placebo-controlled trials and long-term case-control studies demonstrating significant improvements in disease outcomes 2, 4, 3
• UDCA should be started immediately upon diagnosis without waiting for disease progression 3

Benefits of UDCA Treatment

UDCA provides multiple measurable benefits that directly impact disease progression and survival:

• Significantly decreases serum bilirubin, alkaline phosphatase, GGT, cholesterol, and IgM levels compared to placebo 2, 4, 3
• Delays histological progression when started at early stages of disease 2, 4, 3
• Reduces the likelihood of liver transplantation or death in patients with moderate to severe disease 2, 4, 3
• Long-term treatment results in improved transplant-free survival 4

Critical Contraindications

Do not use UDCA in patients with:

• Decompensated cirrhosis (Child-Pugh B or C) 5
• Prior decompensation events 5
• Compensated cirrhosis with evidence of portal hypertension (ascites, gastroesophageal varices, persistent thrombocytopenia) 5

Never use high-dose UDCA (>20 mg/kg/day) as this has been associated with worse outcomes in cholestatic liver diseases 2, 3

Baseline Assessment Before Starting Treatment

Before initiating UDCA, perform the following evaluations:

• Abdominal ultrasound to exclude alternative causes of cholestasis in 90% of patients 1, 3
• Osteoporosis risk assessment as PBC increases fracture risk 1, 3
• Document presence or absence of fatigue and pruritus as these symptoms significantly impact quality of life 1, 3
• Confirm absence of decompensated cirrhosis or portal hypertension 5

Response Assessment After 1 Year

After 1 year of UDCA therapy, perform biochemical response evaluation using validated risk stratification tools:

• Use GLOBE or UK-PBC Risk Scores, which are the most accurate predictive tools 2, 3
• Document response status in 80% of patients receiving UDCA therapy 1, 2
• Regular monitoring of liver biochemistry is essential to assess treatment response 2, 4, 3
• Patients who fail to achieve adequate biochemical response are at higher risk for disease progression and should be considered for second-line therapy 2

Important Limitations of UDCA

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

• Rifampicin for severe pruritus 2
• Bile acid sequestrants 2
• Opioid antagonists (naltrexone, nalmefene) 2
• Sertraline as first-line treatment for cholestatic pruritus 2

Post-Transplant Considerations

If a patient undergoes liver transplantation for PBC, UDCA should be administered lifelong at 10-15 mg/kg/day to prevent disease recurrence 2, 3. Post-transplant UDCA reduces the risk of PBC recurrence and improves graft survival and long-term overall survival 2, 3.

Common Pitfalls to Avoid

• Do not delay treatment initiation while waiting for disease progression—early treatment is critical 2, 4, 3
• Do not use inadequate dosing (<13 mg/kg/day)—this reduces efficacy 1, 2
• Do not use excessive dosing (>20 mg/kg/day)—this worsens outcomes 2, 3
• Do not forget to assess response at 1 year—this identifies patients needing second-line therapy 1, 2, 3
• Do not use UDCA in patients with decompensated cirrhosis or portal hypertension—this is contraindicated 5