What is the treatment for Wilson's disease?

Treatment of Wilson's Disease

Initial treatment for symptomatic patients with Wilson's disease should include a chelating agent (D-penicillamine or trientine), while zinc therapy is appropriate for maintenance treatment or asymptomatic patients. 1

Initial Treatment Options

Chelating Agents (First-line for Symptomatic Patients)

• D-penicillamine is a first-line treatment that promotes urinary excretion of copper and may also act by inducing metallothionein 1, 2
• The maintenance dose of D-penicillamine is usually 750-1500 mg/day administered in two or three divided doses (20 mg/kg/day in children) 1
• D-penicillamine should be administered 1 hour before meals as food inhibits its absorption, and supplemental pyridoxine (25-50 mg/day) should be provided 1
• Trientine is an alternative chelating agent with similar efficacy but potentially fewer side effects than D-penicillamine 1, 3
• Tetrathiomolybdate is an experimental chelating agent that may be preferable for patients with neurological symptoms as it appears less likely to cause neurological deterioration during initial treatment 1, 3

Zinc Therapy

• Zinc is indicated for maintenance treatment of patients with Wilson's disease who have been initially treated with a chelating agent 4
• Zinc appears preferable for presymptomatic children under the age of 3 years 1
• Zinc is more selective for removing copper than penicillamine or trientine and is associated with fewer side effects 1, 3

Treatment Based on Clinical Presentation

Asymptomatic/Presymptomatic Patients

• Treatment with either a chelating agent (D-penicillamine or trientine) or zinc is effective in preventing disease symptoms or progression 1
• Zinc appears preferable for presymptomatic children under the age of 3 years 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
• Patients should be clinically well with normal liver function tests and 24-hour urinary copper in the range of 200-500 μg/day (3-8 μmol/day) before transitioning to maintenance therapy 1

Decompensated Cirrhosis

• Patients with decompensated chronic liver disease may be treated with a combination of a chelator (D-penicillamine or trientine) plus zinc 1
• These treatments must be temporally dispersed throughout the day (typically 5-6 hours apart) to prevent the chelator from binding to zinc 1
• A typical regimen is zinc (50 mg elemental, or 25 mg elemental in children) given as the first and third doses, and trientine (500 mg, or 10 mg/kg in children) given as the second and fourth doses 1

Acute Liver Failure

• Patients with acute liver failure due to Wilson's disease require liver transplantation, which is life-saving 1
• Until transplantation can be performed, plasmapheresis, exchange transfusion, hemofiltration, or dialysis may protect the kidneys from copper-mediated tubular damage 1

Monitoring Treatment

• Adequacy of treatment can be monitored by measuring 24-hour urinary copper excretion 1
• Target values for patients on chelation therapy should be 200-500 μg/day (3-8 μmol/day) 3
• Liver function tests should be monitored every 3 months during the first year of treatment 1

Special Considerations

Pregnancy

• Treatment must be maintained throughout pregnancy for all patients with Wilson's disease as interruption of treatment has resulted in acute liver failure 1
• Both chelating agents (penicillamine and trientine) and zinc salts have been associated with satisfactory outcomes for mother and fetus 1
• The dosage of zinc salts is maintained throughout pregnancy without change, while dosages of chelating agents should be reduced to the minimum necessary during pregnancy, especially for the last trimester 1

Long-term Management

• Treatment for Wilson's disease needs to be life-long once the diagnosis has been made 1
• No matter how well a patient appears, treatment should never be terminated indefinitely as patients who discontinue treatment risk development of intractable hepatic decompensation 1, 3

Important Precautions

• Neurological symptoms may worsen during initiation of therapy with D-penicillamine in 10-50% of patients 3, 2
• Despite this potential worsening, the drug should not be withdrawn as temporary interruption carries an increased risk of developing a sensitivity reaction upon resumption of therapy 2
• Dietary modifications to reduce copper intake should be implemented, especially during the first year of treatment - foods high in copper (shellfish, nuts, chocolate, mushrooms, and organ meats) should generally be avoided 1, 3

Wilson's disease is treatable when diagnosed early, and appropriate therapy can prevent lifelong neurological disabilities and/or cirrhosis 5, 6.