Uneven distribution of hepatic copper concentration and diagnostic value of double-sample biopsy in Wilson's disease

Abstract

Background and aims. Determination of hepatic copper (Cu) concentration is important in Wilson's disease (WD) diagnosis. The aim of this study was to evaluate uneven distribution of liver Cu concentration and the utility of double-sample biopsy in WD diagnosis. Methods. Thirty-five WD patients (20 male; mean age 41 ± 9 years) were enrolled in the study and double-liver samples for biopsy were obtained. A further 30 WD patients, in whom Cu determination was performed using single-liver samples, were also enrolled as controls. Results. A marked difference in hepatic Cu concentration was observed between the two sample groups (p < 0.0001). This difference is statistically significant for all levels of liver fibrosis (p < 0.001) and for the comparison of hepatic and neurological phenotypes (p < 0.01). The sensitivity of the Cu concentrations obtained from the double-sample biopsies for the conventional cut-off value of 250 mg/g dry weight of tissue was 85.7% compared to 80% in the single-sample biopsies. By lowering the cut-off value from 250 to 50 µg/g of dry weight of tissue, the sensitivity of Cu content to diagnose WD increased to 97% for double-sample liver biopsy compared to 93% for single-sample liver biopsy. Conclusions. Liver Cu content was unevenly distributed in the WD subjects, irrespective of fibrosis levels and disease phenotypes; hence WD can be misdiagnosed using single-sample liver Cu measurement. Double-sample biopsy sensitivity is greater than that obtained with single-sample biopsy and should therefore be considered to evaluate liver Cu concentration at initial diagnosis in all patients.

Key Words::

• biopsy
• diagnosis
• hepatic copper
• liver
• Wilson's disease

Acknowledgments

We thank Barry Mark Wheaton for his invaluable linguistic assistance. M Liggi: study concept and design, analysis and interpretation of critical data, revision of the manuscript for important intellectual content, statistical analysis, drafting of the manuscript. C Mais: acquisition of data, analysis and interpretation of critical data, drafting of the manuscript. M Demurtas: acquisition of data, analysis and interpretation of critical data. O Sorbello: revision of the manuscript for important intellectual, administrative, technical content or material support. E Demelia: acquisition of data. A Civolani: revision of the manuscript for important intellectual, administrative, technical content or material support. Luigi Demelia: study supervision.

Declaration of interest: I certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.