8%, 95% CI = 48.6%-80.4%). Moreover, basal urinary copper was directly correlated find more with the age at diagnosis (r = 0.58, P < 0.0001) in children with WD but not in the control group. The daily urinary copper level after PCT did not statistically differ between patients with WD (771.3 ± 103.3 μg/24 hours) and controls (585.5 ± 63.8 μg/24 hours, P = 0.69). Among WD patients, only 3 of 25 (12%) presented values

> 1575 μg/24 hours: all of them had fibrosis at liver biopsy and basal copper excretion > 100 μg/24 hours. Among controls, 3 of 58 (5.2%) had PCT cupriuria > 1575 μg/24 hours, and they presented with NASH, NRH, or AIH type 1. The ROC analysis (area under the curve = 0.61, P = 0.10) of 25 WD patients and 58 controls showed that at the cutoff value of 1575 μg/24 hours, the sensitivity was only 12% (95% CI = 2.5%-31.2%); it was raised to 64% (95% CI = 42.5%-82%) and 88% (95% CI = 68.8%-97.4%) only when the threshold was lowered to >500 μg/24 hours and >200 μg/24 hours, respectively. Liver

copper levels were measured in 30 WD patients and 24 control subjects and significantly differed between the two groups (813.6 ± 81.7 versus 38.4 ± 17 μg/g of dry weight, P < 0.0001). Only 2 of 30 WD patients (7%) had a liver copper level < 75 μg/g of dry weight, which has been proposed as a novel diagnostic threshold19; this website the remaining 28 had values > 250 μg/g of dry weight. Liver copper levels in WD patients did not directly correlate with the severity of the histological picture (data not shown) or the age at liver biopsy (r = 0.38, P = 0.03). Among controls, 4 of 24 (6%)

had liver copper levels > 50 μg/g of dry weight; 2 had CDG (318 and 250 μg/g of dry weight, respectively), 1 had NRH, and 1 had cryptogenic liver disease. The two patients affected by CDG also had low ceruloplasmin levels. The sensitivity and specificity of ceruloplasmin, basal 24-hour urinary copper, and 24-hour urinary copper after PCT at different thresholds are summarized in Table 3. MCE An evaluation of all items of the WD scoring system proposed by Ferenci et al.11 was possible in 30 patients with WD and in 24 control subjects. When the considered cutoff value for basal urinary copper was 40 μg/24 hours, only two patients with WD scored less than 4; when the cutoff value was 100 μg/24 hours, three patients did. Only two control subjects, both of whom had CDG, had a score of 4 regardless of the considered cutoff value (Fig. 3). When we considered 40 μg/24 hours instead of 100 μg/24 hours as the urinary copper ULN, the scoring system had the best diagnostic accuracy: a sensitivity of 93% versus 90%, a specificity of 91.6% versus 91.6%, a positive predictive value of 93% versus 93.1%, and a negative predictive value of 91.6% versus 88%. It is remarkable that all the patients with WD were positive for at least ceruloplasmin or basal urinary copper excretion.