A controlled trial of D-penicillamine therapy in primary biliary cirrhosis.

D-penicillamine, 900 mg daily, was used in a randomised controlled trial for treatment of patients with primary biliary cirrhosis. 19 patients received D-penicillamine and 13 received placebo. The two groups were similar in age, duration of illness, liver function tests, and liver histology. Before entry into the trial liver-copper concentration was raised in 25 of the 27 patients in whom it was measured. After three months patients taking D-penicillamine showed a significant reduction in serum-aspartate-transaminase concentrations compared with the placebo group, and this reduction seemed to be sustained. In the 4 patients on D-penicillamine for a year, a second liver biopsy showed that mean liver-copper concentration fell from 310 +/- 128 (S.E.M.) to 84 +/- 36 microng/g dry liver, compared with a reduction from 511 +/- 169 to 454 +/- 128 in the 7 patients in the placebo group in whom serial liver-copper measurements were available. Liver histology demonstrated a comparative improvement in cholestasis in patients on penicillamine, but the degree of inflammation, necrosis, and the histological stage of disease remained similar in both groups. In 5 of the 19 patients in the D-penicillamine group the drug was discontinued because of side-effects. D-penicillamine seems to be a promising treatment for patients with primary biliary cirrhosis. It may produce its effect by reducing liver-copper concentration.