What is the management of primary biliary cholangitis (PBC)?

Management of Primary Biliary Cholangitis (PBC)

All patients with Primary Biliary Cholangitis should be treated with ursodeoxycholic acid (UDCA) at a dose of 13-15 mg/kg/day as first-line therapy, with second-line options for those with inadequate response. 1

Diagnostic Approach

• Abdominal ultrasound is essential in all patients with suspected PBC to exclude alternative causes of cholestasis (target: 90% of patients) 2
• Diagnosis typically based on:
  • Cholestatic liver biochemistry
  • Presence of antimitochondrial antibodies

Treatment Algorithm

First-line Treatment

• UDCA at 13-15 mg/kg/day for all patients 1
• Continue UDCA lifelong, including after liver transplantation to prevent recurrence 1
• Monitor response after 12 months of therapy using biochemical response indices 1

Assessment of Treatment Response

• Evaluate at 12 months using biochemical markers:
  • Alkaline phosphatase (ALP)
  • Total bilirubin
  • Transaminases (AST/ALT)
  • Albumin
• Monitor these parameters every 3 months 1

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 1
• Elevated GGT >3.2-fold ULN at 12 months
• APRI score >0.54 after 12 months of UDCA therapy 1

Second-line Treatment Options

1. Obeticholic acid (OCA) for patients with inadequate response to UDCA:

   • Starting dose: 5 mg once daily for 3 months
   • May titrate to 10 mg once daily based on tolerability 1
   • Important contraindications:
     • Decompensated cirrhosis (Child-Pugh Class B or C)
     • Prior decompensation events
     • Compensated cirrhosis with evidence of portal hypertension
     • Complete biliary obstruction
     • Bilirubin >3 mg/dL 1, 3

2. Bezafibrate (off-label):

   • Used in combination with UDCA
   • Monitor for myalgia and serum creatinine 1

Management of Symptoms

Pruritus

• Document presence/absence in 90% of patients annually 1
• Treatment options:
  1. First-line: Cholestyramine
  2. Second-line: Rifampicin (with liver monitoring) 1

Fatigue

• Evaluate in 90% of patients annually 1
• Consider psychological support for profound psychological distress 2
• Cognitive behavioral therapy may be beneficial 2

Osteoporosis Prevention

• Risk assessment for all patients with PBC (target: 80% assessment within 5 years) 2, 1
• Treatment according to national osteoporosis guidelines

Monitoring for Disease Progression

Liver Transplantation Consideration

• Discuss with transplant center for patients with:
  • Bilirubin >50 μmol/L
  • Evidence of decompensated liver disease 1

Monitoring for Complications

• Watch for signs of hepatic decompensation:
  • Ascites
  • Jaundice
  • Variceal bleeding
  • Hepatic encephalopathy 3

Patient Support

• Offer patients the opportunity to seek support from patient support groups 2
• Recommend resources such as:
  • The PBC Foundation
  • LIVErNorth
  • Liver4Life 2

Special Considerations

• Pregnancy: UDCA can be continued, but OCA is not recommended 1
• Overlap with autoimmune hepatitis: Rare but should be confirmed with liver biopsy when suspected 2
• Lipid monitoring: OCA can lower HDL-C levels, requiring periodic lipid assessment 3

Treatment Caveats

• FDA has issued a boxed warning for OCA due to reports of hepatic decompensation and failure in PBC patients with cirrhosis 1
• Triple therapy (UDCA, OCA, bezafibrate) may be considered in patients showing inadequate response to dual therapy 4
• The goal of therapy should be normalization of ALP and bilirubin below 0.6 times the upper limit of normal 4, 5