Trial of Penicillamine in Advanced Primary Biliary Cirrhosis

• Published in: The New England journal of medicine Vol. 312; no. 16; pp. 1011 - 1015
• Main Authors: Dickson, E. Rolland, Fleming, C. Richard, Fleming, Thomas R, Wiesner, Russell H, Baldus, William P, Ludwig, Jurgen, McCall, John T
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 18.04.1985
• Subjects: Antigens; Bile; Biological and medical sciences; Clinical Trials as Topic; Copper; Digestive system; Double-Blind Method; Drug dosages; Endoscopy; Family medical history; Female; Follow-Up Studies; Gallbladder diseases; Gastroenterology; Hepatitis; Humans; Internal medicine; Liver - pathology; Liver cirrhosis; Liver Cirrhosis, Biliary - drug therapy; Liver Cirrhosis, Biliary - mortality; Liver Cirrhosis, Biliary - pathology; Liver diseases; Male; Medical sciences; Middle Aged; Patients; Penicillamine - adverse effects; Penicillamine - therapeutic use; Pharmacology. Drug treatments; Phosphatase; Prospective Studies; Random Allocation; Urinalysis; Human; Cirrhosis; Chemotherapy; Treatment; Double blind study; Controlled therapeutic trial; Hepatobiliary disease
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198504183121602

A total of 227 patients with histologically advanced primary biliary cirrhosis entered a double-blind, randomized, controlled trial to determine whether penicillamine (1 g per day) was therapeutically effective; 111 patients received the drug, and 116 received placebo. The two groups were highly comparable at entry with regard to clinical, biochemical, and histologic features. Penicillamine therapy did not result in an overall improvement in survival as compared with placebo. Clinical symptoms and serial hepatic laboratory values reflected the progressive nature of the disease and were similar in both groups. There were no substantial differences between treatment groups in the morphologic features of sequential biopsy specimens. The development of major side effects led to permanent discontinuation of penicillamine in 22 per cent of the patients taking the drug. We conclude that penicillamine is not useful for patients with histologically advanced primary biliary cirrhosis. The trial is being continued in patients with early histologic disease whose better prognosis necessitates longer follow-up. (N Engl J Med 1985; 312: 1011–5.) Primary biliary cirrhosis, a chronic liver disease of unknown cause, is characterized by inflammation and necrosis of intrahepatic bile ducts, cholestasis, cirrhosis, and hepatic failure. 1 The primary pathologic event appears to be destruction of the interlobular bile ducts, which may be mediated by immunologic mechanisms. Increased hepatic copper concentrations, found primarily in advanced disease (histologic Stage 3 or 4), are secondary to progressive intrahepatic cholestasis and diminished hepatobiliary clearance of copper. 2 There is no effective treatment for primary biliary cirrhosis, and the medical approach to patients with the disease has been limited to supportive care. On the basis of the . . .