Long-term exclusive zinc monotherapy in symptomatic Wilson disease: Experience in 17 patients

Abstract

Exclusive monotherapy with zinc in symptomatic Wilson disease is controversial. Seventeen symptomatic patients with Wilson disease were treated with zinc only. The mean age at diagnosis and start of treatment was 18 years (range 13-26) with approximately half presenting as adolescents. Presentation was exclusively hepatic, exclusively neurologic, and combined in seven, five, and five patients, respectively. The median follow-up was 14 years (range 2-30). At baseline, two of the 12 patients with hepatic disease exhibited decompensated cirrhosis, five exhibited compensated cirrhosis, and five had less severe disease. Both patients with decompensated cirrhosis improved to a compensated state after initiation of therapy. Two of the five patients with initial compensated cirrhosis progressed to decompensated state, and three remain stable. Three of the five patients with moderate or mild liver disease remain stable and two improved. Apart from decreasing bilirubin levels, no significant changes occurred in the liver biochemistry or function during long-term follow-up. Nine of 10 neurologic patients improved markedly and one deteriorated. Two patients with exclusively neurologic presentation developed liver disease during zinc treatment. Two patients with exclusively hepatic presentation developed mild neurologic symptoms. According to 24-hour urinary copper excretions (213 ؎ 38 versus 91 ؎ 23 g: P ‫؍‬ 0.01) and serum non-ceruloplasmin-bound copper concentrations (11 ؎ 2 versus 7 ؎ 1 g/dL: P ‫؍‬ 0.1) at the end of follow-up, the efficacy of decoppering was less in the exclusively hepatic than in the neurologic group. The prescribed zinc dose and 24-hour urinary zinc excretions tended to be less in the exclusively hepatic group. Conclusion: The outcome of exclusive zinc therapy is generally good in cases of neurologic disease. A less satisfactory outcome in hepatic disease may relate to less efficient decoppering.

Evolving Perspectives in Wilson Disease: Diagnosis, Treatment and Monitoring

“…We found a significantly higher rate of inadequate response to therapy (in terms of worsening of liver function tests and increasing urinary copper excretion) in patients using zinc than with chelation treatment. Concerning the elevation of ALT and GGT, these findings are in line with a recently published series of 17 patients who showed a similar, but not statistically significant, trend with zinc monotherapy [53]. Constitutional risk factors for the failure of zinc therapy were not evident in our cohort [13••], as this event was not associated with sex, genotype, presentation, degree of liver dysfunction or age.…”

“…Consistently a lower or at least comparable rate of neurologic deterioration of neurologic patients with zinc monotherapy has been reported [42,[53][54][55]. However, studies or case series of patients receiving zinc salt as primary treatment are often restricted to asymptomatic [56,57] or only neurologically [42,55] affected patients.…”

Resolution of Cranial MRI and SPECT Abnormalities in a Patient with Wilson's Disease Following Oral Zinc Monotherapy

“…The present patient improved neurologically after her medication regimen was switched to zinc acetate, and repeated MRI showed a marked improvement in all brain and brainstem lesions. In a therapeutic study of long-term zinc monotherapy in patients with WD, exclusive zinc therapy generally yielded satisfactory results for neurological disease (10). To the best of our knowledge, apart from the present case, the improvement of T2WI signal alteration on follow-up brain MRIs has been documented in only two reported cases of WD patients undergoing zinc treatment (11,12).…”

Chronic hepatitis in man and in dog: a comparative update

“…The consequent progressive copper accumulation ultimately compromise hepatic function; when the hepatic storage capacity is 206 exceeded, unbound copper spills out of the liver and is deposited in other organs and tissues, where it also provokes damage and dysfunction. Chelating agents such as penicillamine, promoting copper excretion, represent the principal therapeutic weapon for Wilson's disease; zinc acetate is commonly used in maintaining therapy after copper depletion and has been shown to be effective in neurological syndrome and in children (49).…”