Treatment of Wilson's Disease
The primary treatment for Wilson's disease consists of copper chelating agents (D-penicillamine or trientine) for symptomatic patients, while zinc therapy may be used for maintenance treatment or as first-line therapy in neurological patients. 1, 2
Initial Treatment Based on Clinical Presentation
Symptomatic Hepatic Disease
- D-penicillamine or trientine is recommended as first-line therapy for patients with hepatic symptoms 2
- Zinc monotherapy is not recommended for symptomatic liver disease due to reports of hepatic deterioration and even fatal outcomes 2
- Typical dosage of D-penicillamine is 750-1500 mg/day administered in two or three divided doses, taken 1 hour before meals 1
- For children, D-penicillamine dosing is 20 mg/kg/day in divided doses 1
- Trientine dosage is typically 750-1500 mg/day in two or three divided doses, with 750-1000 mg used for maintenance therapy 1
Neurological Presentation
- Zinc may be preferred as first-line therapy in patients with neurological symptoms as neurological deterioration is uncommon with zinc therapy 2
- Tetrathiomolybdate is an experimental chelating agent that may be preferable for patients with neuropsychiatric symptoms as it appears less likely to cause neurological deterioration 3
- Neurological worsening can occur in 10-50% of patients during early phase of treatment with chelating agents, particularly D-penicillamine 3
Acute Liver Failure
- Liver transplantation is the only effective treatment option for patients with acute liver failure due to Wilson's disease 2
- Until transplantation can be performed, plasmapheresis, hemofiltration, exchange transfusion, or dialysis may protect the kidneys from copper-mediated tubular damage 1
Decompensated Cirrhosis
- Patients with decompensated chronic liver disease may be treated with a combination of chelator (D-penicillamine or trientine) plus zinc 1
- The two types of treatment must be temporally dispersed (5-6 hours between doses) to avoid having the chelator bind the zinc 1
- A typical regimen is zinc (50 mg elemental, or 25 mg elemental in children) given as first and third doses, and trientine (500 mg, or 10 mg/kg in children) given as second and fourth doses 1
Asymptomatic/Presymptomatic Patients
- Either zinc or a chelating agent is effective in preventing disease symptoms or progression 1
- Zinc appears preferable for presymptomatic children under the age of 3 years 1
- Treatment with D-penicillamine or zinc has been shown to effectively prevent disease symptoms or progression 1
Maintenance Therapy
- After adequate treatment with a chelator (typically 1-5 years), stable patients may be continued on a lower dosage of the chelating agent or shifted to treatment with zinc 1
- Zinc is more selective for removing copper than penicillamine or trientine and is associated with fewer side effects 1
- Dosage for adults: 150 mg elemental zinc daily in three divided doses 2
- Dosage for children (<50 kg): 75 mg/day in three divided doses 2
Monitoring Treatment
- Adequacy of treatment can be monitored by measuring 24-hour urinary copper excretion 1
- For patients on chelators, 24-hour urinary copper excretion should be 200-500 μg/day (3-8 μmol/day) 2
- For patients on zinc, urinary copper excretion should be no more than 75 μg/day (1.2 μmol/day) 2
- Non-ceruloplasmin bound copper concentration should normalize with effective treatment 1
- Patients should be monitored at least twice yearly, more frequently during initial treatment phase 2
Special Considerations
Pregnancy
- Treatment must be maintained throughout pregnancy for all patients with Wilson's disease 1
- Interruption of treatment during pregnancy has resulted in acute liver failure 1
- Zinc dosage is maintained without change during pregnancy 2
- Dosages of chelating agents should be reduced to the minimum necessary during pregnancy, especially for the last trimester 1
- For patients with Wilson's disease on D-penicillamine, it is recommended that the daily dosage be limited to 750 mg during pregnancy 4
Side Effects and Monitoring
- D-penicillamine can cause hypersensitivity reactions, bone marrow suppression, proteinuria, and autoimmune disorders 4
- Trientine has fewer side effects than D-penicillamine but can cause iron deficiency and pancytopenia in rare cases 1
- Zinc's most common side effect is gastric irritation 2
- Liver function tests and indices of copper metabolism should be monitored regularly 2
Important Pitfalls to Avoid
- Treatment must never be terminated indefinitely, even if symptoms resolve, as interruption of treatment has resulted in fulminant hepatic failure 3
- Non-compliance with treatment can lead to hepatic deterioration and is a major problem, especially in adolescents 5
- Overtreatment can lead to copper deficiency, resulting in neutropenia, anemia, and hyperferritinemia 2
- When using combination treatment with chelator plus zinc, careful timing (5-6 hours between doses) is essential to avoid having the chelator bind to zinc 1