What is Wilson's disease (Hepatolenticular degeneration)?

From the Guidelines

Wilson's disease patients should be treated with lifelong copper chelation therapy, with penicillamine, trientine, or zinc acetate being the primary treatment options, as they have been shown to dramatically improve symptoms and induce long-term remission in most patients with chronic liver disease 1. When managing Wilson's disease, it is essential to consider the potential complications, including neurological dysfunction, hemolytic anemia, and renal involvement. The choice of medication depends on symptom severity and side effect profiles, with penicillamine being the most effective for acute copper removal but having more side effects, while trientine is better tolerated 1. Key aspects of treatment include:

• Lifelong copper chelation therapy with medications like penicillamine, trientine, or zinc acetate
• Initial dose of penicillamine: 250-500mg daily, gradually increased to 1000-1500mg daily in divided doses
• Dose of trientine: 1000-2000mg daily in divided doses
• Dose of zinc acetate: 50mg three times daily
• Low-copper diet, avoiding foods like liver, shellfish, chocolate, nuts, and mushrooms
• Regular monitoring, including liver function tests, complete blood counts, 24-hour urinary copper excretion, and free serum copper levels every 3-6 months Liver transplantation is necessary only for patients with decompensated cirrhosis who fail to respond to medical therapy or for those who present with fulminant hepatic failure, as it can reverse all of the metabolic abnormalities associated with Wilson disease and improve survival rates, which have ranged from 80% to 90% 1 year after transplantation 1.

From the FDA Drug Label

Wilson's disease (hepatolenticular degeneration) occurs in individuals who have inherited an autosomal-recessive defect that leads to an accumulation of copper far in excess of metabolic requirements The excess copper is deposited in several organs and tissues, and eventually produces pathological effects primarily in the liver, where damage progresses to postnecrotic cirrhosis, and in the brain, where degeneration is widespread Two types of patients require treatment for Wilson's disease: (1) the symptomatic, and (2) the asymptomatic in whom it can be assumed the disease will develop in the future if the patient is not treated Treatment has two objectives: (1) to minimize dietary intake of copper; (2) to promote excretion and complex formation (i.e., detoxification) of excess tissue copper.

Wilson's Disease Treatment

• The treatment objectives are to minimize dietary intake of copper and promote excretion of excess tissue copper.
• A copper chelating agent, such as penicillamine or trientine, is used to achieve the second objective.
• In symptomatic patients, treatment usually produces marked neurologic improvement, fading of Kayser-Fleischer rings, and gradual amelioration of hepatic dysfunction and psychic disturbances.
• Treatment of asymptomatic patients has been carried out for over 30 years, and symptoms and signs of the disease appear to be prevented indefinitely if daily treatment with penicillamine or trientine is continued 2, 3.

From the Research

Overview of Wilson's Disease

• Wilson's disease is an autosomal recessive disorder related to copper metabolism, causing copper deposition in various tissues such as the liver, brain, kidney, and cornea 4.
• The clinical symptoms of Wilson's disease are due to copper toxicity in these tissues 4, 5, 6, 7.

Treatment and Management

• The key strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering copper-chelating agents and a low copper diet 4.
• D-Penicillamine is considered the first choice as a copper-chelating agent, with a daily dose of 15-25 mg/kg in the early stages of treatment 4.
• Trientine is also used as a copper-chelating agent, particularly when D-penicillamine has to be withdrawn due to side effects, with a daily dose of 40-50 mg/kg 4, 8.
• Zinc salt administration is used as a supportive therapy, with a daily dose of 5-7.5 mg/kg, to inhibit copper absorption 4, 5, 6.
• Liver transplantation is an option for patients with fulminant or chronic progressive types of Wilson's disease 4, 7, 8.

Therapeutic Goals and Challenges

• The therapeutic goal is to normalize free copper in serum, which is achievable by inducing metallothionein with chelators and zinc 5.
• A challenge in the treatment of Wilson's disease is the full restoration of neurological deficits, which can be difficult to achieve with available chelators 5, 8.
• The use of bis-choline-tetrathiomolybdate as an intracellular copper chelator is being explored as a potential option for treating Wilson's disease 5.

Efficacy and Safety of Treatments

• Chelating agents such as D-penicillamine and trientine are effective therapies for most patients with Wilson's disease, with comparable outcomes 8.
• However, D-penicillamine has a higher rate of adverse events compared to trientine, including systemic lupus erythematosus and nephrotic syndrome 4, 8.
• Neurologic deterioration is less frequent in patients treated with D-penicillamine compared to those treated with trientine 8.