How to manage pruritus (itching) in patients with fatty liver disease?

Management of Pruritus in Fatty Liver Disease

For patients with fatty liver disease experiencing pruritus, rifampicin is recommended as first-line therapy due to its proven efficacy and safety profile in hepatic pruritus. 1

Pathophysiology and Clinical Presentation

Pruritus in fatty liver disease is primarily related to cholestasis, though the exact mechanism remains incompletely understood. Recent evidence suggests that:

• Autotaxin enzyme and lysophosphatidic acid may play key roles in cholestatic pruritus 2
• Bile acid retention alone does not fully explain pruritus severity 3
• Pruritus often worsens in the evening and night
• Common locations include palms, soles, and can become generalized 4

Treatment Algorithm

First-line Treatment:

• Rifampicin (300-600 mg/day)
  • Start at 150 mg once to twice daily
  • Titrate upwards based on symptoms and liver function tests
  • Maximum dose: 600 mg daily
  • Monitor liver function tests after 2-4 weeks of treatment
  • Use with caution in advanced liver disease 1

Second-line Treatment:

• Cholestyramine (4 g/day to maximum 16 g/day)
  • Administration: Give at breakfast time (1 hour before or after eating)
  • Must be taken 2-4 hours apart from other medications including UDCA
  • Mixing with orange squash and refrigerating overnight improves palatability
  • Monitor for constipation 1

Third-line Treatment:

• Sertraline (100 mg/day)
  • Titrate dose according to symptoms and tolerance
  • Side effects include dry mouth 1

Fourth-line Treatment:

• Naltrexone (50 mg/day)
  • Start at 12.5 mg/day and titrate slowly
  • Monitor for opiate withdrawal-like reactions
  • Some patients may require intravenous induction 1

Fifth-line Treatments:

• Consider:
  • Systemic dronabinol
  • Phenobarbitone
  • Propofol
  • Topical tacrolimus ointment 1

Special Considerations

Treatments to Avoid:

• Gabapentin is specifically NOT recommended for hepatic pruritus 1
• Sedative antihistamines should be avoided long-term except in palliative care due to dementia risk 1

Non-pharmacological Approaches:

• Broadband UVB (BB-UVB) phototherapy is effective for cholestatic pruritus 1
• Transcutaneous electrical nerve stimulation may benefit patients with hepatic pruritus 1
• Combined UVA and UVB therapy may provide relief 1

Experimental Approaches (for refractory cases):

• Extracorporeal dialysis techniques
• Nasobiliary drainage
• Liver transplantation (for persistent, intractable pruritus) 1

Monitoring and Follow-up

• Assess response to therapy after 2-4 weeks
• For rifampicin: Monitor liver function tests regularly due to potential hepatotoxicity
• Consider vitamin K supplementation if patient is icteric while on rifampicin 1
• If pruritus remains intractable despite multiple therapeutic trials, consider referral for liver transplantation evaluation 1

Pitfalls and Caveats

• Rapid weight loss in NAFLD patients can worsen portal inflammation and fibrosis; aim for gradual weight reduction (<1 kg/week) 1, 5
• Obeticholic acid, while effective for NASH, can cause severe itching and increased LDL-C, potentially outweighing benefits 1
• When using cholestyramine, be aware of potential drug interactions; separate administration from other medications 6
• Antihistamines have limited specific efficacy for hepatic pruritus but may be useful adjuncts due to sedative properties 1

The management of pruritus in fatty liver disease requires a systematic approach with careful monitoring of treatment efficacy and side effects. Rifampicin has demonstrated the strongest evidence for efficacy in hepatic pruritus and should be considered first-line therapy when appropriate.