What treatment options are available for a patient with pruritus and decompensated liver (liver) disease?

Treatment of Pruritus in Decompensated Liver Disease

Rifampicin should be considered as first-line treatment for pruritus in patients with decompensated liver disease, starting at 150 mg twice daily and potentially increasing to 600 mg twice daily as needed. 1

Treatment Algorithm for Hepatic Pruritus

First-line Treatment:

• Rifampicin: 150 mg twice daily initially, with potential increase to 600 mg twice daily 1
  • Requires close monitoring for hepatotoxicity with liver function tests every 2-4 weeks 2
  • Two meta-analyses support rifampicin's effectiveness in reducing hepatic pruritus 1
  • Monitor for side effects including change in color of secretions (orange-red urine, tears, sweat)

Second-line Treatment:

• Cholestyramine: 9 g daily orally 1
  • Binds bile salts in the gut lumen, preventing absorption in terminal ileum
  • Should be administered at least 4 hours apart from other medications
  • Common side effects include constipation and GI discomfort

Third-line Treatment:

• Sertraline: 75-100 mg daily orally 1
  • Well-tolerated in patients with hepatic pruritus
  • One small RCT supports its efficacy 1

Fourth-line Treatment:

• Opioid antagonists: Naltrexone 50 mg daily orally or nalmefene (0.25-1 mg/kg/day IV) 1
  • Associated with more side effects than cholestyramine and rifampicin
  • May cause opioid withdrawal-like symptoms initially

Fifth-line Options:

• Systemic dronabinol
• Phenobarbital
• Propofol
• Topical tacrolimus ointment 1

Important Considerations and Cautions

Monitoring for Rifampicin Therapy

• Liver function tests: Prior to therapy and every 2-4 weeks during treatment 2
• Signs of hepatotoxicity: Jaundice, fatigue, abdominal pain, nausea
• Discontinue immediately if signs of hepatic damage occur or worsen 2

Risk of Rifampicin-Induced Hepatitis

• Significant hepatitis occurs in approximately 7.3% of patients treated for cholestatic liver disease 3
• Can lead to impaired hepatic synthetic function in severe cases 3
• Particularly concerning in patients with pre-existing decompensated liver disease

Medications to Avoid

• Gabapentin: Not recommended in hepatic pruritus 1
• Ondansetron: Insufficient evidence to support routine use 1

Clinical Presentation of Hepatic Pruritus

• Often worse in evenings and early night
• Commonly affects palms and soles but can be generalized 4
• Skin may be hyperpigmented and excoriated, particularly hands and feet 1
• Pruritus with fatigue may indicate more aggressive liver disease 1

Pathophysiology and Mechanisms

The pathogenesis of cholestatic pruritus is complex and not fully understood. Potential contributors include:

• Bile salts accumulation
• Autotaxin (enzyme producing lysophosphatidic acid) 4
• Opioid system dysregulation
• Histamine and progesterone metabolites 4

For patients with severe, treatment-resistant pruritus, experimental therapies such as UV light therapy or nasobiliary drainage may be considered in specialized centers 4, 5.

Remember that pruritus in decompensated liver disease significantly impacts quality of life and requires prompt, effective management with careful monitoring of liver function throughout treatment.