Treatment of Wilson's Disease

Initial Treatment Based on Presentation

Symptomatic patients with Wilson's disease should receive a chelating agent (D-penicillamine or trientine) as first-line therapy, while zinc may be used as first-line therapy in neurological patients or for maintenance treatment, as recommended by the American Association for the Study of Liver Diseases 1, 2
D-penicillamine or trientine is recommended as first-line therapy for patients with hepatic symptoms, according to the European Association for the Study of the Liver 1, 2
Zinc monotherapy is not recommended for symptomatic liver disease due to reports of hepatic deterioration and even fatal outcomes, as stated by the American Association for the Study of Liver Diseases 1
For patients with acute liver failure due to Wilson's disease, liver transplantation is the only effective treatment option, as indicated by the American Association for the Study of Liver Diseases 3
Zinc may have a role as first-line therapy in patients with neurological symptoms, as suggested by the European Association for the Study of the Liver 1, 2
Neurological deterioration is uncommon with zinc therapy, according to the American Association for the Study of Liver Diseases 4

Treatment with either zinc or a chelating agent is effective in preventing disease symptoms or progression, as recommended by the American Association for the Study of Liver Diseases 5
Zinc appears preferable for presymptomatic children under the age of 3 years, according to the European Association for the Study of the Liver 6

Zinc induces enterocyte metallothionein which binds copper and prevents its absorption, as described by the American Association for the Study of Liver Diseases 4
Dosage for adults and larger children: 150 mg elemental zinc daily in three divided doses, as recommended by the American Association for the Study of Liver Diseases 5, 4
Dosage for smaller children (<50 kg): 75 mg/day in three divided doses, according to the European Association for the Study of the Liver 5, 4
Side effects are minimal, with gastric irritation being the most common, as reported by the American Association for the Study of Liver Diseases 2

Patients should be monitored at least twice yearly, more frequently during initial treatment phase, as recommended by the American Association for the Study of Liver Diseases 7
Laboratory testing should include liver function tests and indices of copper metabolism, according to the European Association for the Study of the Liver 7
For patients on chelators, 24-hour urinary copper excretion should be 200-500 μg/day (3-8 μmol/day), as indicated by the American Association for the Study of Liver Diseases 7
For patients on zinc, urinary copper excretion should be no more than 75 μg/day (1.2 μmol/day), as recommended by the American Association for the Study of Liver Diseases 7

Avoid foods with high copper concentrations (shellfish, nuts, chocolate, mushrooms, organ meats), as recommended by the American Association for the Study of Liver Diseases 5
Dietary management alone is not recommended as sole therapy, according to the European Association for the Study of the Liver 5
Vitamin E may have a role as adjunctive treatment, as suggested by the American Association for the Study of Liver Diseases 5, 2
Serum and hepatic vitamin E levels are often low in Wilson's disease, as reported by the American Association for the Study of Liver Diseases 5, 2

Treatment must be maintained throughout pregnancy, as recommended by the American Association for the Study of Liver Diseases 3
Interruption of treatment during pregnancy has resulted in acute liver failure, according to the American Association for the Study of Liver Diseases 3
Zinc dosage is maintained without change during pregnancy, as indicated by the European Association for the Study of the Liver 3
Dosages of chelating agents should be reduced by 25-50% during the last trimester, as recommended by the American Association for the Study of Liver Diseases 3
Liver transplantation is indicated for acute liver failure and decompensated cirrhosis unresponsive to medical therapy, according to the American Association for the Study of Liver Diseases 3
One-year survival following liver transplantation ranges from 79-87%, as reported by the American Association for the Study of Liver Diseases 3

Combination treatment with chelator plus zinc requires careful timing (5-6 hours between doses) to avoid having the chelator bind to zinc, as recommended by the American Association for the Study of Liver Diseases 3
Non-compliance with treatment can lead to hepatic deterioration, according to the European Association for the Study of the Liver 7
Overtreatment can lead to copper deficiency, resulting in neutropenia, anemia, and hyperferritinemia, as reported by the American Association for the Study of Liver Diseases 7