Hepatic copper accumulates in ferrets with and without hepatobiliary disease

OBJECTIVE To determine hepatic copper concentrations and zonal distribution in ferrets with and without hepatobiliary disease, validate rhodanine-based qualitative copper scoring and digital copper quantification in ferret hepatic samples, and ascertain whether clinical features predicted copper accumulation. ANIMALS 34 ferrets, including 7 with necroinflammatory disease, 5 with hepatocellular carcinoma, 13 with non-necroinflam-matory disease, and 9 with no hepatobiliary disease. PROCEDURES Rhodanine-based digital copper quantification was validated by use of liver dually measured by atomic absorption spectroscopy and digital scanning (R-2 = 0.98). Clinical features and hepatic copper scores and concentrations (dry weight liver) were compared between groups. Zonal copper distribution was determined. RESULTS Hepatic copper concentration was strongly correlated with copper scores (p = 0.88). Ferrets with hepatobiliary disease were significantly older and had significantly higher serum alkaline phosphatase and gamma-glutamyltransferase activities and creatinine concentrations. Centrilobular copper accumulated in 23 of 34 (64%) ferrets with (n = 15) and without (8) hepatobiliary disease. Median copper concentrations were not significantly different between ferrets with and without hepatobiliary disease but were significantly higher within neoplastic hepatic tissue in ferrets with hepatocellular carcinoma. Hepatic copper concentrations exceeded feline (> 180 mu g/g) and canine (> 400 mu g/g) reference limits in 19 and 9 ferrets, respectively. Hepatic copper > 1,000 mu g/g occurred in 5 ferrets with and 2 without hepatobiliary disease. Clinical features did not predict copper accumulation.