Hepatic organelle pathology in primary biliary cirrhosis and the response to low-dose D-penicillamine therapy.

1. Analytical subcellular fractionation in combination with enzymic microanalysis has been used to investigate the hepatic organelle pathology of primary biliary cirrhosis. Activities of plasma membrane and lysosomal enzymes in hepatic needle biopsies were increased, but marker enzymes for other organelles were normal. 2. Seven patients were treated with a low dose of penicillamine, 250 mg daily, over a 3--6 month period. The initially raised serum alkaline phosphatase and IgM levels were significantly reduced. In four patients with markedly elevated hepatic copper there was a small decrease, but urinary copper excretion was unaltered. Hepatic organelle pathology was significantly improved. 3. No serious side-effects were noted and it is suggested that a controlled trial of low-dose D-penicillamine therapy is indicated in patients with primary biliary cirrhosis.