What is the treatment for Wilson disease?

Treatment of Wilson Disease

The first-line treatment for Wilson disease is a chelating agent, with trientine being preferred over D-penicillamine due to its better safety profile, at a dosage of 750-1500 mg/day in 2-3 divided doses for adults. 1

Initial Treatment Approach

Symptomatic Patients

1. Chelation therapy:

   • Trientine: 750-1500 mg/day in 2-3 divided doses (first-line) 1
   • D-penicillamine: 750-1500 mg/day in 2-3 divided doses (alternative) 2, 1
     • Add pyridoxine (vitamin B6) 25-50 mg daily with D-penicillamine 1
     • Note: D-penicillamine has severe side effects in ~30% of patients 1

2. For patients with decompensated cirrhosis without encephalopathy:

   • Combination therapy: Chelator + zinc (separated by 5-6 hours) 2
   • Typical regimen: Zinc (50 mg elemental) as first and third doses, trientine (500 mg) as second and fourth doses 2
   • May transition to monotherapy after 3-6 months if responding 1

3. For acute liver failure:

   • Liver transplantation is life-saving and definitive 2, 1
   • While awaiting transplant: Plasmapheresis, hemofiltration, or albumin dialysis 2, 1
   • Nazer prognostic score ≥7 indicates poor survival without transplant 1

Asymptomatic/Presymptomatic Patients

• Zinc therapy: Preferred for presymptomatic children under 3 years 2
• Chelating agents (D-penicillamine or trientine) are also effective 2

Maintenance Therapy

After 1-5 years of successful chelation therapy, patients may transition to zinc maintenance therapy if they are:

• Clinically well
• Have normal liver function tests
• Normal non-ceruloplasmin bound copper
• 24-hour urinary copper in the range of 200-500 μg/day on treatment 2, 1

Monitoring Treatment

• Frequency: At minimum twice yearly, more frequently during initial treatment phase 2
• Physical examination: Look for evidence of liver disease and neurological symptoms 2
• Laboratory monitoring:
  • Liver function tests: Every 3 months during first year, then every 3-6 months 1
  • 24-hour urinary copper excretion:
    • On chelation therapy: Target 200-500 μg/day 2, 1
    • On zinc therapy: Target <75 μg/day 1
  • Non-ceruloplasmin bound copper: Should normalize with effective treatment 1
  • Urinary zinc excretion (~2 mg/24 hours): To ensure compliance with zinc therapy 1

Special Considerations

Pregnancy

• Treatment must be maintained throughout pregnancy 2, 1
• Zinc salts: Maintain same dosage throughout pregnancy 2, 1
• Chelating agents: Reduce dosage by 25-50% during the last trimester 2, 1
• Women taking D-penicillamine should not breast-feed 2

Neurological Disease

• Neurological worsening can occur in two patterns 3:
  • Early worsening (≤3 months): Treatment-associated, occurs in 26.1% of neurological patients
  • Late worsening (>12 months): Often associated with non-adherence
• Liver transplantation is not recommended as primary treatment for neurologic WD 2

Dietary Management

• Avoid foods high in copper: shellfish, nuts, chocolate, mushrooms, organ meats 1
• Check copper content of water if using copper pipes 1
• Dietary management alone is insufficient and must be combined with medical treatment 1

Important Warnings and Pitfalls

• Never discontinue treatment indefinitely - this can lead to serious complications including fulminant hepatic failure 2, 1
• Do not administer zinc and chelators simultaneously - separate by at least 5-6 hours 1
• Monitor for side effects:
  • D-penicillamine: Proteinuria, rash, bone marrow depression 1, 4
  • Trientine: Sideroblastic anemia (rare) 1
  • Zinc: Gastric irritation 1
• Watch for neurological deterioration after initiating therapy, which can occur with all treatments but may be more common with D-penicillamine 2, 3

Wilson disease treatment is lifelong, and interruption of therapy has been associated with acute liver failure and other serious complications. Regular monitoring is essential to ensure treatment efficacy and detect potential adverse effects early.