Metallothionein and copper in liver disease with copper retention—a histopathological study

Abstract

We have examined the relationship between (a) histochemically demonstrable copper using rubeanic add, (b) copper-associated protein (CAP) using orcein, and (c) immunoreactive metallothionein (MT) using DNP hapten sandwich staining and have correlated these with histological lesions in 95 liver biopsies from patients with conditions associated with hepatic copper retention, 4 fetal livers, and 25 historically normal adult controls. No copper or CAP was present in normal adult liver but periportal CAP was present in fetal liver. MT was present in hepatocytes of normal livers with a predominantly perivenular (centrilobular) cytoplasmic distribution varying in staining intensify; all fetal hepatocytes stained strongly for MT. Fifty-two of 95 (55 per cent) abnormal livers contained CAP and 42 (44 per cent) contained both CAP and copper. In CAP-positive livers, the commonest histological lesions were piecemeal necrosis and cholestasis. CAP was present in (a) 15/15 cases of primary biliary cirrhosis including early cases with minimal pathology; and (b) 5/5 cases of Wilson's disease, 6/6 cases of biliary atresia, and 3/9 cases of sclerosing cholangitis. In other conditions, it was present in 25–50 per cent of cases. MT distribution was abnormal in most CAP-positive livers. Necrotic hepatocytes were intensely MT-positive and in Wilson's disease had a characteristic appearance.