• Open Access

Association between Liver Copper Concentration and Subclinical Hepatitis in Doberman Pinschers


Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, University Utrecht, Yalelaan 8, 3584 CM Utrecht, The Netherlands; e-mail: p.j.j.mandigers@vet.uu.nl.


The prevalence of subclinical hepatitis was investigated in a group of 106 randomly selected 3-year-old Doberman Pinschers. Histopathologic examination of liver samples from 65 dogs (52 dogs with high bile acids, alkaline phosphatase activity, or alanine aminotransferase activity or with copper granules in hepatocytes in a liver aspirate and 13 normal dogs) revealed subclinical hepatitis in 22 dogs (19 females and 3 males). Liver copper concentrations measured by instrumental neutron activation analysis was significantly higher (mean ± SD; 419 ± 414 μg/g dry matter) in dogs with hepatitis than those without liver disease (197 ± 113 μg/g; P= .0008). At 2.6 ± 0.6 years hepatitis persisted in 5 of 16 dogs available for examination. One dog with a high copper concentration but normal liver subsequently developed subclinical hepatitis after 3 years. During the follow-up period, the average copper concentration of the 6 dogs with persistent subclinical hepatitis was 939 ± 299 μg/g and had continued to rise significantly (P= .02). The hepatitis in these dogs was associated with apoptotic hepatocytes and copper-laden Kupffer cells in centrolobular regions. The results of this study suggest that there is a relationship among copper storage, hepatocellular damage, and hepatitis in Doberman Pinschers.