Relative Exchangeable and Exchangeable Copper: Emerging New Biomarkers for Diagnosis and Therapy Monitoring in...

Wilson's disease (WD) is a genetic disorder of copper metabolism in which early diagnosis remains challenging, particularly in acute liver failure (ALF). Relative exchangeable copper (REC) and exchangeable copper (CuEXC) are emerging biomarkers for diagnosis and monitoring, but data from larger cohorts are limited. This monocentric retrospective cohort study evaluated the diagnostic accuracy of REC in WD patients, including adult ALF and assessed the utility of CuEXC during monitoring.

299 paediatric/adult patients with liver disease were analysed; 215 had confirmed WD (Leipzig score ≥ 4). Clinical data, parameters of copper metabolism and liver function tests were collected. REC was analysed in the full cohort. CuEXC was evaluated longitudinally at three standardized timepoints over 12 months in treated adult WD patients and compared with 24-h urinary copper excretion (UCE) after 48-h treatment interruption.

REC demonstrated excellent diagnostic accuracy with an AUC of 0.955 (sensitivity 88.4%, specificity 91.7%). In adult ALF, REC perfectly discriminated WD (n = 2/2, 100%) from other causes. CuEXC declined significantly in therapy-naïve patients and differentiated these from very stable patients, but showed limited discrimination between stable versus unstable patients during median follow-up. UCE off-treatment showed parallel trajectories to CuEXC.

REC is a highly accurate diagnostic biomarker for WD, including adult ALF. CuEXC is useful to characterize initial treatment response and copper control, but its role as a routine monitoring biomarker between stable and unstable patients remains uncertain and requires prospective validation, whereas UCE remains as a robust follow-up parameter in these patients.