{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:08:49Z","timestamp":1787656129437,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:00:00Z","timestamp":1523923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>In Wilson disease (<jats:styled-content style=\"fixed-case\">WD<\/jats:styled-content>), copper accumulates in the liver and other tissues because of mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>7B<\/jats:italic> copper transporter gene. Early and effective anticopper treatment is crucial. However, routine diagnostic methods based on clinical findings, copper metabolism tests, liver biopsies and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> analyses do not always provide a conclusive diagnosis. The aim was to evaluate radioactive copper incorporation as a diagnostic test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included cases with a diagnosis of <jats:styled-content style=\"fixed-case\">WD<\/jats:styled-content> supported by radiocopper testing and later, when available, confirmed by <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> analysis. Incorporation of <jats:sup>64<\/jats:sup>Cu was measured at 2, 24 and 48\u00a0hours following intravenous injection. Diagnostic accuracy (area under the receiver operating characteristic curve [<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>]), sensitivity, specificity and predictive value were assessed for 24\u00a0hours\/2\u00a0hours and 48\u00a0hours\/2\u00a0hours <jats:sup>64<\/jats:sup>Cu ratios and compared with serum measurements of ceruloplasmin, copper, non\u2010ceruloplasmin\u2010bound copper and urinary 24\u2010hours copper excretion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients having two pathogenic <jats:italic><jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>7B<\/jats:italic> mutations (homozygotes\/compound heterozygotes) (n\u00a0=\u00a074) had significantly lower 24\u00a0hours\/2\u00a0hours and 48\u00a0hours\/2\u00a0hours <jats:sup>64<\/jats:sup>Cu ratios than heterozygote controls (n\u00a0=\u00a021) (mean 0.14 and 0.12 vs 0.49 and 0.63, respectively; both <jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>.001). Of note, 24\u00a0hours\/2\u00a0hours and 48\u00a0hours\/2\u00a0hours <jats:sup>64<\/jats:sup>Cu ratios had excellent diagnostic accuracy, with <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>s approaching 1, and only 24\u2010hours urinary copper excretion displayed similar positive features. Other copper metabolism tests studied had lower accuracy, specificity and sensitivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The radioactive copper test had excellent diagnostic accuracy and may be useful in the evaluation of new therapies aimed at restoring <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>7B function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13715","type":"journal-article","created":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T13:26:40Z","timestamp":1518096400000},"page":"1860-1866","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Accuracy of the radioactive copper incorporation test in the diagnosis of Wilson disease"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1956-1866","authenticated-orcid":false,"given":"Anna","family":"Cz\u0142onkowska","sequence":"first","affiliation":[{"name":"2nd Department of Neurology Institute of Psychiatry and Neurology  Warsaw Poland"},{"name":"Department of Experimental and Clinical Pharmacology Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rodo","sequence":"additional","affiliation":[{"name":"Department of Genetics Institute of Psychiatry and Neurology  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Wierzchowska\u2010Ciok","sequence":"additional","affiliation":[{"name":"2nd Department of Neurology Institute of Psychiatry and Neurology  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Smolinski","sequence":"additional","affiliation":[{"name":"2nd Department of Neurology Institute of Psychiatry and Neurology  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Litwin","sequence":"additional","affiliation":[{"name":"2nd Department of Neurology Institute of Psychiatry and Neurology  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00004.2006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-7500-8_11"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2014.05.007"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70190-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22261"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.11.007"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S79121"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.55.8.692"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12320"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00868525"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0676.2003.00824.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63625-6.00014-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2016-310960"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63625-6.00003-3"},{"key":"e_1_2_9_16_1","first-page":"13","article-title":"Uptake of radiocopper by the liver. A study of patients with Wilson's disease and various control groups","volume":"24","author":"Osborne SB","year":"1963","journal-title":"Clin Sci"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(72)90100-3"},{"key":"e_1_2_9_18_1","first-page":"175","article-title":"Observation on copper metabolism in Wilson's disease","volume":"56","author":"Cz\u0142onkowska A","year":"1973","journal-title":"Acta Univ Carol Med Monogr"},{"key":"e_1_2_9_19_1","first-page":"79","volume-title":"Proceedings of the 5th Symposium on Wilson's Disease","author":"Bachamnn H","year":"1991"},{"key":"e_1_2_9_20_1","first-page":"21","volume-title":"Proceedings of the 5th Symposium on Wilson's Disease","author":"Van den Hamer CJ","year":"1991"},{"key":"e_1_2_9_21_1","first-page":"87","volume-title":"Proceedings of the 5th Symposium on Wilson's Disease","author":"Siegemund R","year":"1991"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12041-010-0065-3"},{"key":"e_1_2_9_23_1","first-page":"161","article-title":"An improved colorimetric enzymatic assay for ceruloplasmin","volume":"58","author":"Ravin HA","year":"1961","journal-title":"J Lab Clin Med"},{"key":"e_1_2_9_24_1","volume-title":"Wilson's Disease","author":"Scheinberg IH","year":"1984"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13171"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt035"},{"key":"e_1_2_9_27_1","article-title":"Neurological presentations revealing acquired copper deficiency: diagnosis features, etiologies and evolution in seven patients","author":"Poujois A","year":"2017","journal-title":"Intern Med\u00a0J"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12020"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pjnns.2014.05.002"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2007.11.001"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004563216676843"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(17)30293-5"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-81186-9_1"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41430-017-0002-0"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1070692"},{"key":"e_1_2_9_36_1","first-page":"84","article-title":"64Cu loading tests for monitoring zinc therapy in Wilson's disease","volume":"1","author":"Van den Hamer CJA","year":"1984","journal-title":"Trace Elem Med"},{"key":"e_1_2_9_37_1","first-page":"659","article-title":"Wilson disease. Comparative ultrastructure in a sibship of nine","volume":"100","author":"Lough J","year":"1976","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-009-9145-6"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.111.092361"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-25151"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.09.014"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.11.017"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.3155"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.13715","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.13715","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T18:15:40Z","timestamp":1694715340000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.13715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,17]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1111\/liv.13715"],"URL":"https:\/\/doi.org\/10.1111\/liv.13715","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,17]]},"assertion":[{"value":"2017-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}