Clinical Features of Seven Cases of Copper-Associated Hepatitis in Dalmatians in Japan

Abstract

We investigated the clinical features of seven cases of copper-associated hepatitis in Dalmatians that occurred in Japan. The average age of the onset of all cases was 22 months old, and these cases commonly developed non-specific symptoms of anorexia and weight loss, accompanied by gastrointestinal symptoms of diarrhea and vomiting. Polydipsia was observed in four cases, and jaundice was in two most advanced cases. All the cases showed marked increases in blood concentrations of liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST). Diagnostic imaging of abdominal cavity showed no abnormal findings. Histopathological examinations of the liver in three cases revealed multifocal necrosis of hepatocytes and chronic hepatitis with severe copper accumulation in hepatocytes. Quantitative analysis of the copper level of the liver specimen of these three cases showed severe copper accumulation of more than 10,000 μg/g. Clinical symptoms and blood liver enzyme concentrations were improved after administering oral copper-chelating agents of penicillamine in two cases. Based on these results, this disease should be considered as one of the differential diagnoses for young Dalmatians showing gastrointestinal symptoms and severely increased blood concentrations of liver enzymes, and appropriate diagnostic modalities and treatment methods should be taken.