D-penicillamine treatment improves survival in primary biliary cirrhosis.

The copper-chelating, immunological, and antifibrotic effects of D-penicillamine indicated that it might be suitable for the treatment of primary biliary cirrhosis (PBC). In a randomised clinical trail, 55 PBC patients received penicillamine (600 mg daily), and 32 received a placebo. Drug reactions developed in 16 patients on penicillamine. All deaths occurred in patients with stage 3 or 4 (late stage) liver histology on entry to the study. 5 (14%) of 37 penicillamine-treated patients and 10 (43%) of 23 placebo patients have died (p less than 0.01). Improvement in survival only became evident after 18 months. Survivors in the penicillamine group demonstrated a significant fall in serum aspartate transaminase, serum immunoglobulins, and liver copper concentrations. On follow-up liver biopsy 12-72 months (median 33) after joining the study, 21% of penicillamine-treated patients had less pronounced inflammation and piecemeal necrosis, whereas there had been no improvement in patients on placebo (p less than 0.02). Penicillamine did not retard the histological evolution of the liver disease from the early prefibrotic stages to the late fibrotic or cirrhotic stages. Both the copper-chelating and immunological effects of penicillamine are probably important in improving survival. The excellent prognosis of patients with PBC in its early histological stages, and the failure of penicillamine to prevent histological progression from early to late stages, suggests that penicillamine treatment should not be given to patients with PBC in the early (stage 1 or 2) histological phase of the disease. Penicillamine treatment is recommended in patients once liver biopsy has demonstrated histological results typical of late stage 3 or 4 PBC.

RCT Entities:   Population Interventions Outcomes