{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:32:38Z","timestamp":1788622358115,"version":"build-2803163510"},"reference-count":28,"publisher":"American Veterinary Medical Association (AVMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["javma"],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>Objective<\/jats:bold>\u2014To determine signalments, clinical features, clinicopathologic variables, imaging findings, treatments, and survival time of cats with presumed primary copper-associated hepatopathy (PCH) and to determine quantitative measures and histologic characteristics of the accumulation and distribution of copper in liver samples of cats with presumed PCH, extrahepatic bile duct obstruction, chronic nonsuppurative cholangitis-cholangiohepatitis, and miscellaneous other hepatobiliary disorders and liver samples of cats without hepatobiliary disease.<\/jats:p>\n<jats:p><jats:bold>Design<\/jats:bold>\u2014Retrospective cross-sectional study.<\/jats:p>\n<jats:p><jats:bold>Animals<\/jats:bold>\u2014100 cats with hepatobiliary disease (PCH [n = 11], extrahepatic bile duct obstruction [14], cholangitis-cholangiohepatitis [37], and miscellaneous hepatobiliary disorders [38]) and 14 cats without hepatobiliary disease.<\/jats:p>\n<jats:p><jats:bold>Procedures<\/jats:bold>\u2014From 1980 to 2013, cats with and without hepatobiliary disease confirmed by liver biopsy and measurement of hepatic copper concentrations were identified. Clinical, clinicopathologic, and imaging data were compared between cats with and without PCH.<\/jats:p>\n<jats:p><jats:bold>Results<\/jats:bold>\u2014Cats with PCH were typically young (median age, 2.0 years); clinicopathologic and imaging characteristics were similar to those of cats with other liver disorders. Copper-specific staining patterns and quantification of copper in liver samples confirmed PCH (on the basis of detection of &gt; 700 \u03bcg\/g of liver sample dry weight). Six cats with PCH underwent successful treatment with chelation (penicillamine; n = 5), antioxidants (5), low doses of elemental zinc (2), and feeding of hepatic support or high-protein, low-carbohydrate diets, and other hepatic support treatments. One cat that received penicillamine developed hemolytic anemia, which resolved after discontinuation of administration. Three cats with high hepatic copper concentrations developed hepatocellular neoplasia.<\/jats:p>\n<jats:p><jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014Results suggested that copper accumulates in livers of cats as primary and secondary processes. Long-term management of cats with PCH was possible.<\/jats:p>","DOI":"10.2460\/javma.244.1.68","type":"journal-article","created":{"date-parts":[[2013,12,17]],"date-time":"2013-12-17T21:15:49Z","timestamp":1387314949000},"page":"68-77","source":"Crossref","is-referenced-by-count":30,"title":["Presumed primary and secondary hepatic copper accumulation in cats"],"prefix":"10.2460","volume":"244","author":[{"given":"Brandi M.","family":"Hurwitz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon A.","family":"Center","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Randolph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P.","family":"McDonough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen 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Rep","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11894-011-0227-3","article-title":"Evolving perspectives in Wilson disease: diagnosis, treatment and monitoring","volume":"14","author":"Weiss","year":"2012"},{"key":"ref4","series-title":"Gastroenterol Hepatol (NY)","first-page":"438","article-title":"Wilson disease and hepatocellular carcinoma","volume":"4","author":"Xu","year":"2008"},{"key":"ref5","series-title":"Hum Mol Genet","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1093\/hmg\/8.3.501","article-title":"Genetic mapping of the copper toxicosis locus in Bedlington Terriers to dog chromosome 10, in a region syntenic to human chromosome region 2p13-p16","volume":"8","author":"van de Sluis","year":"1999"},{"key":"ref6","series-title":"J Vet Diagn Invest","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1177\/104063870001200201","article-title":"A perspective on copper and liver disease in the dog","volume":"12","author":"Thornburg","year":"2000"},{"key":"ref7","series-title":"Vet Pathol","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1177\/030098589503200414","article-title":"Hepatopathy associated with excessive hepatic copper in a Siamese cat","volume":"32","author":"Haynes","year":"1995"},{"key":"ref8","series-title":"Vet Pathol","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1354\/vp.42-1-97","article-title":"Copper-associated chronic hepatitis and cirrhosis in a European Shorthair cat","volume":"42","author":"Meertens","year":"2005"},{"key":"ref9","series-title":"Hokkaido Igaku Zasshi","first-page":"331","article-title":"Copper and liver injury: experimental studies of the dogs with biliary obstruction and copper loading","volume":"57","author":"Azumi","year":"1982"},{"key":"ref10","series-title":"Comp Hepatol","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1476-5926-2-5","article-title":"Animal models of copper-associated liver disease","volume":"2","author":"Fuentealba","year":"2003"},{"key":"ref11","series-title":"J Vet Diagn Invest","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1177\/1040638712445765","article-title":"Hepatic copper and iron accumulation and histologic findings in 104 feline liver biopsies","volume":"24","author":"Whittemore","year":"2012"},{"key":"ref12","series-title":"J Nutr","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1093\/jn\/113.10.1963","article-title":"Selected features of copper metabolism in the cat","volume":"113","author":"Doong","year":"1983"},{"key":"ref13","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.2460\/ajvr.74.12.1474","article-title":"Digital image analysis of rhodanine stained canine liver biopsies for calculation of hepatic copper concentrations","volume":"74","author":"Center","year":"2013"},{"key":"ref14","series-title":"Am J Vet Res","first-page":"1822","article-title":"Hematologic and biochemical abnormalities associated with induced extrahepatic bile duct obstruction in the cat","volume":"44","author":"Center","year":"1983"},{"key":"ref15","series-title":"Vet Pathol","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1177\/0300985810384409","article-title":"Histopathologic features, immunophenotyping, clonality, and eubacterial fluorescence in situ hybridization in cats with lymphocytic cholangitis\/cholangiohepatitis","volume":"48","author":"Warren","year":"2011"},{"key":"ref16","series-title":"Vet Clin North Am Small Anim Pract","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.cvsm.2004.10.002","article-title":"Feline hepatic lipidosis","volume":"35","author":"Center","year":"2005"},{"key":"ref17","series-title":"MacSween's pathology of the liver","first-page":"1","article-title":"Anatomy, pathophysiology, and basic mechanisms of disease","author":"Crawford","year":"2012"},{"key":"ref18","series-title":"Hepatology","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1002\/hep.1840160434","article-title":"Congenital diseases of intrahepatic bile ducts: variations on the theme \u201cductal plate malformation.\u201d","volume":"16","author":"Desmet","year":"1992"},{"key":"ref19","series-title":"J Am Vet Med Assoc","doi-asserted-by":"publisher","first-page":"372","DOI":"10.2460\/javma.242.3.372","article-title":"Hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis: 72 cases (1980\u20132010)","volume":"242","author":"Johnston","year":"2013"},{"key":"ref20","series-title":"Vet Pathol","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1354\/vp.07-VP-0097-I-FL","article-title":"The progenitor cell compartment in the feline liver: an (immuno)histochemical investigation","volume":"46","author":"Ijzer","year":"2009"},{"key":"ref21","series-title":"J Am Vet Med Assoc","doi-asserted-by":"publisher","first-page":"246","DOI":"10.2460\/javma.229.2.246","article-title":"Vacuolar hepatopathy in dogs: 336 cases (1993\u20132005)","volume":"229","author":"Sepesy","year":"2006"},{"key":"ref22","series-title":"Am J Pathol","first-page":"715","article-title":"The significance of variations in the distribution of copper in liver disease","volume":"99","author":"Goldfischer","year":"1980"},{"key":"ref23","series-title":"Gastroenterol Jpn","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/BF02782948","article-title":"Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson's disease and biliary diseases","volume":"23","author":"Miyamura","year":"1988"},{"key":"ref24","series-title":"J Nutr","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1093\/jn\/130.5.1287","article-title":"Dietary copper influences reproduction in cats","volume":"130","author":"Fascetti","year":"2000"},{"key":"ref25","series-title":"Aust Vet J","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1111\/j.1751-0813.1983.tb02815.x","article-title":"Copper storage disease with intravascular haemolysis in a Bedlington Terrier","volume":"60","author":"Watson","year":"1983"},{"key":"ref26","series-title":"Pediatr Transplant","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1111\/j.1399-3046.2006.00562.x","article-title":"Hepatocellular carcinoma in Wilson's disease: a rare association in childhood","volume":"10","author":"Savas","year":"2006"},{"key":"ref27","series-title":"Hepatology","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1053\/jhep.2000.17705","article-title":"Hepatocellular carcinoma cell cycle: study of Long-Evans cinnamon rats","volume":"32","author":"Masaki","year":"2000"},{"key":"ref28","series-title":"Hepatology","first-page":"614","article-title":"Prevention of spontaneous hepatocellular carcinoma in Long-Evans cinnamon rats with hereditary hepatitis by the administration of d-penicillamine","volume":"18","author":"Jong-Hon","year":"1993"}],"container-title":["Journal of the American Veterinary Medical 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