Diagnostic Value of Quantitative Hepatic Copper Determination in Patients With Wilson's Disease

Background & Aims: A 5-fold increase of hepatic copper concentration is considered as the best available test for diagnosis of hepatic Wilson's disease (WD). However, the sensitivity and specificity of this test have never been fully investigated. Methods: Copper content was measured by flame atomic absorption spectroscopy in 114 liver biopsies obtained at diagnosis of WD, in 219 patients with noncholestatic liver diseases (including 144 with chronic hepatitis C and 44 with nonalcoholic fatty liver disease), and in 26 without evidence of liver disease. Results: Liver copper content was >250 μg/g in 95 WD patients (83.3%), between 50 and 250 μg/g in 15, and below 50 μg/g in 4. It did not correlate with age (r2 = .003), the grade of fibrosis, or the presence of stainable copper. Liver copper content was >250 or between 50 and 250 μg/g in 3 (1.4%) and 20 (9.1%) of 219 patients with noncholestatic liver diseases, respectively. By lowering the cutoff from 250 to 75 μg/g, the sensitivity of liver copper content to diagnose WD increased from 83.3% (95% confidence interval, 75.2%-89.6%) to 96.5% (91.3%-99.1%), but the specificity decreased from 98.6% (96.0%-99.7%) to 95.4% (91.8%-97.8%). Conclusions: There is no gold standard for the diagnosis of WD. Liver copper content is a useful parameter, but a value below 250 μg/g does not exclude WD. Diagnosis requires the combination of a variety of clinical and biochemical tests.