{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T16:01:05Z","timestamp":1765382465175,"version":"build-2065373602"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T00:00:00Z","timestamp":1699142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Record"],"published-print":{"date-parts":[[2024,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Copper\u2010associated chronic hepatitis (CuCH) is poorly characterised in Cavalier King Charles spaniels (CKCS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Hepatic copper accumulation was qualitatively and quantitatively assessed, and blood samples were used for genetic testing to screen for known CuCH\u2010associated genetic variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The study included 13 CKCS with CuCH and eight unaffected controls. Increased transaminase activities, elevated biliary enzyme concentrations and portal hypertension were documented in 100%, 73% and 38% of dogs with CuCH, respectively. Five dogs had three or more abnormalities in measures of liver function. All 11 dogs with CuCh that underwent genetic testing were homozygous negative for the\n                      <jats:italic>COMMD1<\/jats:italic>\n                      deletion and\n                      <jats:italic>ATP7A<\/jats:italic>\n                      variant but homozygous positive (\n                      <jats:italic>n<\/jats:italic>\n                      = 7) or heterozygous (\n                      <jats:italic>n<\/jats:italic>\n                      = 4) for the\n                      <jats:italic>ATP7B<\/jats:italic>\n                      variant. Liver histology often demonstrated marked architectural distortion by severe, bridging fibrosis and regenerative nodules with lymphoplasmacytic inflammation. Centrilobular copper accumulation characterised early cases with minimal fibrosis. When fibrosis was significant, copper was often differentially concentrated within regenerative nodules. Chelation therapy resolved laboratory derangements and portal hypertension in five of seven dogs. Of the 7 non\u2010surviving dogs with CuCH, 6 had not received chelation therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Limitations<\/jats:title>\n                    <jats:p>Limitations include a small cohort size and the lack of pedigree analyses to corroborate heritability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CuCH should be considered in CKCS with suspected liver disease. Long\u2010term prognosis seems favourable in dogs receiving chelation therapy, notwithstanding the presence of previously reported negative prognostic markers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/vetr.3561","type":"journal-article","created":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T22:56:31Z","timestamp":1699224991000},"source":"Crossref","is-referenced-by-count":3,"title":["Copper\u2010associated chronic hepatitis in Cavalier King Charles spaniels"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5523-6411","authenticated-orcid":false,"given":"Ran","family":"Nivy","sequence":"first","affiliation":[{"name":"Ben\u2010Shemen Specialist Referral Centre Ben\u2010Shemen Israel"},{"name":"Koret School of Veterinary Medicine The Hebrew University of Jerusalem  Rehovot 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