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

Treatment of Primary Biliary Cholangitis (PBC)

Ursodeoxycholic acid (UDCA) at a dose of 13-15 mg/kg/day is the first-line treatment for all patients with Primary Biliary Cholangitis and should be offered to every patient upon diagnosis. 1

First-Line Treatment

• UDCA is the cornerstone of PBC therapy with strong evidence supporting its use:
  • Recommended dose: 13-15 mg/kg/day, divided into two doses
  • Standard of care: 90% of patients should receive adequate UDCA dosing or be documented as intolerant 1
  • Long-term benefits: Improves liver biochemistry, delays histological progression, and increases transplant-free survival 2, 3

Monitoring Treatment Response

After initiating UDCA therapy, response should be assessed at 12 months using biochemical response indices:

• Key monitoring parameters:

  • Alkaline phosphatase (ALP)
  • Bilirubin
  • Transaminases (AST/ALT)
  • Albumin
  • Monitor every 3 months 4

• Inadequate response criteria (any of the following):

  • ALP ≥1.67 × upper limit of normal (ULN)
  • Total bilirubin >ULN
  • Less than 15% reduction in ALP from baseline 4

Second-Line Therapy for UDCA Non-Responders

For patients with inadequate response to UDCA after 12 months:

1. Obeticholic acid (OCA) - FDA and EMA approved second-line therapy:

   • Starting dose: 5 mg once daily for 3 months
   • Can be titrated to 10 mg once daily based on tolerability and response 4
   • Important safety warning: Contraindicated in patients with decompensated cirrhosis (Child-Pugh Class B or C), prior decompensation events, or complete biliary obstruction due to risk of liver failure 4, 5

2. Bezafibrate - Used off-label in combination with UDCA:

   • Has shown efficacy in reducing ALP levels and improving pruritus
   • Requires monitoring of serum creatinine and watching for myalgia 4
   • Not FDA approved for this indication but supported by clinical evidence 6

Management of Symptoms

1. Pruritus:

   • Common symptom requiring specific management
   • First-line: Cholestyramine
   • Second-line: Rifampicin (with liver monitoring)
   • Document presence/absence of pruritus in 90% of patients annually 1

2. Fatigue:

   • Evaluate for presence in 90% of patients annually 1
   • Consider psychological support for patients with profound psychological distress associated with fatigue 1

Monitoring for Complications

1. Osteoporosis:

   • Risk assessment for all patients with PBC
   • 80% of patients should have assessment within 5 years of diagnosis 1
   • Treatment according to national osteoporosis guidelines

2. Liver transplantation consideration:

   • All patients with bilirubin >50 μmol/L or evidence of decompensated liver disease should be discussed with a transplant center 1

Special Considerations

1. Post-transplant management:

   • UDCA should be given lifelong after liver transplantation to prevent recurrence 1
   • No specific immunosuppressive regimen is recommended over another to prevent recurrence 1

2. Pregnancy:

   • UDCA can be continued during pregnancy 4
   • OCA is not recommended during pregnancy due to lack of safety data 4

Common Pitfalls to Avoid

1. Inadequate UDCA dosing:

   • Ensure proper weight-based dosing (13-15 mg/kg/day)
   • Underdosing may lead to suboptimal response

2. Delayed recognition of non-response:

   • Failure to assess treatment response at 12 months
   • Missing the window for timely second-line therapy initiation

3. Overlooking OCA contraindications:

   • Using OCA in patients with decompensated cirrhosis can lead to fatal outcomes
   • Always assess liver function before initiating OCA 5

4. Neglecting symptom management:

   • Symptoms like pruritus and fatigue significantly impact quality of life
   • Proactive management improves patient outcomes and satisfaction

By following this evidence-based approach to PBC management, clinicians can optimize outcomes and improve quality of life for patients with this chronic liver disease.