Zinc inhibits intestinal copper uptake, an effect utilized for treating Wilson’s disease (WD). We used copper-64 (64Cu) PET/CT to examine how much four weeks of treatment with different zinc regimens reduced the hepatic 64Cu content after oral 64Cu administration and test if alternative regimens were noninferior to the standard regimen of zinc acetate 50 mg × 3 daily. Forty healthy persons were randomized to four different zinc protocols. The WD standard treatment zinc acetate 50 mg × 3 reduced the hepatic 64Cu content from 26.9 ± 7.5% to 13.3 ± 5.6% of the administered 64Cu. Zinc gluconate 50 mg × 3 was noninferior (P = 0.02) (35.8 ± 9.0% to 17.4 ± 7.5%). Zinc acetate 150 mg × 1 (33.1 ± 9.9% to 17.4 ± 7.5%) and zinc gluconate 150 mg × 1 (28.1 ± 6.7% to 22.0 ± 6.7%) were less effective. These effects were intra- and inter-individually highly variable, and 14% had no effect of any zinc regimen, which may explain disparities in zinc treatment efficacy in WD patients.

Background: In Wilson disease (WD), mutations in the gene encoding the ATP7B copper transport protein causes accumulation of copper especially in liver and brain. WD typically presents with hepatic and/or neuropsychiatric symptoms. Impaired cognition is a well-described feature in patients neurological WD, while the reports on cognition in hepatic WD patients are fewer and less conclusive. We examined cognition in a cohort of WD patients with both phenotypes. Methods: In this cross-sectional pilot study, we investigated cognition in 28 stable Danish WD patients by portosystemic encephalopathy (PSE) and continuous reaction time (CRT) tests. Half of the patients were female and median age was 35.5 years (IQR 24.5). The phenotype was hepatic in 14 (50%), neurologic in 10 (36%) and mixed in 4 4 (14%). The duration of treatment was >2 year in all patients, and the condition stable as judged by urinary copper excretion, liver enzymes, and clinical assessment.Results: In total, 16 (57%) patients performed worse than normal in the PSE and/or CRT tests. The two tests correlated (rho=0.60, p=0.0007) with each other, but neither correlated with phenotype, MELD-, Child-Pugh score, 24h-U-Cu, or treatment type.Conclusion: Measurable cognitive impairment was present in more than half of the stable WD patients independent of phenotype. Thus, our data questions the existence of a purely hepatic phenotype.

Background: In Wilson disease (WD), mutations in the gene encoding the ATP7B copper transport protein causes accumulation of copper especially in liver and brain. WD typically presents with hepatic and/or neuropsychiatric symptoms. Impaired cognition is a well-described feature in patients neurological WD, while the reports on cognition in hepatic WD patients are fewer and less conclusive. We examined cognition in a cohort of WD patients with both phenotypes.Methods: In this cross-sectional pilot study, we investigated cognition in 28 stable Danish WD patients by portosystemic encephalopathy (PSE) and continuous reaction time (CRT) tests. Half of the patients were female and median age was 35.5 years (IQR 24.5). The phenotype was hepatic in 14 (50%), neurologic in 10 (36%) and mixed in 4 4 (14%). The duration of treatment was >2 year in all patients, and the condition stable as judged by urinary copper excretion, liver enzymes, and clinical assessment.Results: In total, 16 (57%) patients performed worse than normal in the PSE and/or CRT tests. The two tests correlated (rho=0.60, p=0.0007) with each other, but neither correlated with phenotype, MELD-, Child-Pugh score, 24h-U-Cu, or treatment type. Conclusion:Measurable cognitive impairment was present in more than half of the stable WD patients independent of phenotype. Thus, our data questions the existence of a purely hepatic phenotype.

No abstract