TREATMENT Wilson’s Disease
Recommended anticopper treatments are listed in Table 408-2. Penicillamine was previously the primary anticopper treatment but now plays only a minor role because of its toxicity and because it often worsens existing neurologic disease if used as initial therapy. If penicillamine is given, it should always be accompanied by pyridoxine (25 mg/d). Trientine is a less toxic chelator and is supplanting penicillamine when a chelator is indicated.
For patients with hepatitis or cirrhosis but without evidence of hepatic decompensation or neurologic/psychiatric symptoms, zinc is the therapy of choice although some experts advocate therapy with trientine. Zinc has proven efficacy in Wilson’s disease and is essentially nontoxic. It produces a negative copper balance by blocking intestinal absorption of copper, and it induces hepatic metallothionein synthesis, thereby sequestering additional toxic copper. All presymptomatic patients should be treated prophylactically because the disease is close to 100% penetrant.
The first step in evaluating patients presenting with hepatic decompensation is to establish disease severity, which can be estimated with the Nazer prognostic index (Table 408-3). Patients with scores <7 can usually be managed with medical therapy. Patients with scores >9 should be considered immediately for liver transplantation. For patients with scores between 7 and 9, clinical judgment is required in deciding whether to recommend transplantation or medical therapy. A combination of trientine and zinc has been used to treat patients with Nazer scores as high as 9, but such patients should be watched carefully for indications of hepatic deterioration, which mandates transplantation.
For initial medical treatment of patients with hepatic decompensation, the recommended regimen is a chelator (preferably trientine) plus zinc (Table 408-2). Zinc should not, however, be ingested simultaneously with trientine, which chelates zinc and forms therapeutically ineffective complexes. Administration of the two drugs should be separated by at least 1 h.
For initial neurologic therapy, tetrathiomolybdate is emerging as the drug of choice because of its rapid control of free copper, preservation of neurologic function, and low toxicity. Penicillamine and trientine should be avoided because both have a high risk of worsening the neurologic condition. Until tetrathiomolybdate is commercially available, zinc therapy is recommended. Although it is relatively slow-acting, zinc itself does not exacerbate neurologic abnormalities. Although hepatic transplantation may alleviate neurologic symptoms, it does so only by copper removal, which can be done more safely and inexpensively with anticopper drugs. Pregnant patients should be treated with zinc or trientine throughout pregnancy but without tight copper control because copper deficiency can be teratogenic.
Anticopper therapy must be lifelong. With treatment, liver function usually recovers after about a year although residual liver damage is usually present. Neurologic and psychiatric symptoms usually improve after 6–24 months of treatment.