| Title: |
Evaluation of novel assays of non-ceruloplasmin copper to monitor chelation treatment in patients with Wilson disease: Monitoring chelation treatment in Wilson disease. |
| Authors: |
Ott, Peter; Sandahl, Thomas; Ala, Aftab; Cassiman, David; Couchonnal-Bedoya, Eduardo; Cury, Rubens Gisbert; Czlonkowska, Anna; Denk, Gerald; D'Inca, Renata; Gondim, Francisco de Assis Aquino; Moore, Joanna; Poujois, Aurelia; Twardowschy, Carlos Alexandre; Weiss, Karl Heinz; Zuin, Massimo; Kamlin, C. Omar F.; Schilsky, Michael L. |
| Source: |
ISSN:2589-5559 ; JHEP Rep. |
| Publication Year: |
2026 |
| Subject Terms: |
Exchangeable copper; bioavailable copper; free serum copper; protein speciation. Accurate non-ceruloplasmin copper; 3202 Clinical sciences |
| Description: |
BACKGROUND: We examined the use of two newer measures of non-ceruloplasmin bound copper (NCC) and 24-hour urinary Cu excretion (UCE) to monitor chelation therapy in clinically stable Wilson Disease (WD). METHODS: We post-hoc analyzed data from Chelate study, in which 77 clinically stable WD patients on penicillamine (DPA) entered a 12-week screening phase after which 53 were randomized to continued DPA or same dose trientine-tetrahydrochloride (TETA4) (weeks 12-60). Data included NCC measured by protein speciation (NCC-Sp), exchangeable copper (NCC-Ex), and UCE. RESULTS: In 32/53 patients with unchanged dose from week 1 to 60, NCC-Sp decreased from 57.9±21.1μg/L to 39.6±16.25μg/L (P=0.0002), while NCC-Ex decreased from 56.4±20.3μg/L to 46.2±11.5(P=0.01), likely due to improved adherence during participation in a clinical trial. UCE dropped by ∼50% after switching to TETA4 and gradually decreased in the DPA arm. Biomarker values did not reach steady state until week 60. The visit-to-visit coefficient of variance was 30% for NCC-Sp, 20% for NCC-Ex and 52% for UCE. Including all 45 patients who completed week 60, those with lower tertile values of NCC-Sp (16.3-30.9μg/L) and NCC-Ex (18.7-43.1μg/L) had lower and more stable AST and ALT, and higher and more stable S-Albumin and S-Protein than those with higher values. No neurological changes were noted despite these differences in NCC. Copper deficiency was not observed. CONCLUSION: Non-ceruloplasmin by protein speciation and exchangeable copper have potential to guide chelation in WD patients on maintenance therapy. Specific target ranges should be established, and we hypothesize they may include values below normal ranges. Further studies are required to improve our understanding of the responses to dose changes and non-adherence and if standardization of sampling conditions can reduce visit-to-visit variability. TRIAL NO: (NCT03539952) IMPACT AND IMPLICATIONS: The use of biomarkers of copper metabolism (non-ceruloplasmin and 24 hour urinary copper excretion) to ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://lirias.kuleuven.be/handle/20.500.12942/784296; https://doi.org/10.1016/j.jhepr.2026.101822; https://pubmed.ncbi.nlm.nih.gov/41831608 |
| DOI: |
10.1016/j.jhepr.2026.101822 |
| Availability: |
https://lirias.kuleuven.be/handle/20.500.12942/784296; https://hdl.handle.net/20.500.12942/784296; https://lirias.kuleuven.be/retrieve/6c766962-6900-4493-9b4d-6d035253897d; https://doi.org/10.1016/j.jhepr.2026.101822; https://pubmed.ncbi.nlm.nih.gov/41831608 |
| Rights: |
info:eu-repo/semantics/openAccess ; public |
| Accession Number: |
edsbas.9B56FCA0 |
| Database: |
BASE |