What are the treatment options for cholestasis?

Treatment Options for Cholestasis

Bezafibrate or rifampicin is the recommended first-line pharmacological treatment for cholestasis-associated pruritus, particularly in sclerosing cholangitis and other forms of fibrosing cholangiopathy. 1

Diagnostic Approach

Before initiating treatment, a systematic diagnostic approach is essential to determine the underlying cause of cholestasis:

1. Differentiate intrahepatic vs. extrahepatic cholestasis:

   • Abdominal ultrasound is mandatory as the first-line imaging procedure 1, 2
   • If ultrasound is inconclusive, MRCP or EUS should be performed (preferred over diagnostic ERCP due to ERCP's complication risks) 1, 2

2. Laboratory testing:

   • Test for antimitochondrial antibodies (AMA) in adults with chronic intrahepatic cholestasis 1, 2
   • If AMA negative, consider MRCP to evaluate for PSC and other biliary tract abnormalities 1
   • Liver biopsy may be needed for unexplained intrahepatic cholestasis 1

Treatment Algorithm for Cholestasis

1. Treat Underlying Cause

• Extrahepatic obstruction: Requires prompt intervention
  • Bile duct stones: Endoscopic removal
  • Strictures: Endoscopic balloon dilation or stenting 1
  • Tumors: Surgical or endoscopic decompression 3

2. Pharmacological Management for Cholestatic Pruritus

• First-line therapy:

  • Bezafibrate: Demonstrated clear benefit in the FITCH trial for moderate to severe cholestasis-associated pruritus 1
  • Rifampicin (150-300 mg daily): Alternative first-line option 1

• Second-line options:

  • Naltrexone (12.5-50 mg daily): Start at very low doses (12.5 mg) to avoid opioid withdrawal-like side effects 1
  • Sertraline (25-75 mg daily): Limited data for sclerosing cholangitis-associated itch 1

• Previously recommended but now less favored:

  • Cholestyramine (4-16 g/day): Limited evidence in sclerosing cholangitis compared to PBC; can impair absorption of other medications like UDCA 1

3. Non-Pharmacological Management for Pruritus

• Use emollients to prevent skin dryness
• Avoid hot baths or showers
• Apply cooling gels (e.g., menthol gels) to affected skin areas
• Keep nails shortened 1

4. Disease-Specific Treatments

• Primary Biliary Cholangitis (PBC):

  • Ursodeoxycholic acid (UDCA) at 13-15 mg/kg/day 1, 2
  • Obeticholic acid for patients with inadequate response to UDCA 4

• Primary Sclerosing Cholangitis (PSC):

  • Endoscopic treatment of dominant strictures 1
  • Bezafibrate in combination with UDCA for anticholestatic effects 1

Monitoring and Adverse Effects

Bezafibrate

• Monitor serum creatinine (may increase mildly)
• Watch for myalgia and myopathies (though not observed in short-term FITCH trial)
• Check serum transaminases periodically 1

Rifampicin

• May induce drug-induced hepatitis after 4-12 weeks in up to 12% of cholestatic patients
• First 2 weeks generally considered safe
• Regular liver function monitoring required 1

Obeticholic Acid

• Severe pruritus reported in 23% of patients receiving 10 mg dose
• Monitor for reduction in HDL-C levels
• Permanently discontinue in patients who develop hepatic decompensation 4

Special Considerations

1. Pregnancy-related cholestasis (ICP):

   • Characterized by intense pruritus in second/third trimester
   • Elevated serum ALT and fasting bile acid levels
   • Spontaneous relief after delivery 1

2. Drug-induced cholestasis:

   • Prompt withdrawal of suspected drug is crucial
   • UDCA may benefit some cases
   • Corticosteroids may help in hypersensitivity-induced cholestasis 1

3. Psychological impact:

   • Cholestasis-associated symptoms, particularly pruritus, can significantly impair quality of life
   • Consider psychological support and referral to patient support groups 1

By addressing both the underlying cause and managing symptoms like pruritus, treatment of cholestasis can significantly improve patient quality of life and potentially slow disease progression.