A prospective clinical trial of D-penicillamine in the treatment of primary biliary cirrhosis

Authors

  • Henry C. Bodenheimer Jr. M.D.,

    Corresponding author
    1. Department of Medicine, Division of Gastroenterology, Brown University and Rhode Island Hospital, Providence, Rhode Island 02902; Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029; and Liver Research Center Albert Einstein College of Medicine, Bronx, New York 10461
    • Department of Medicine, Division of Gastroenterology, Rhode Island Hospital, 593 Eddy Street, APC Room 421, Providence, Rhode Island 02902
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  • Fenton Schaffner,

    1. Department of Medicine, Division of Gastroenterology, Brown University and Rhode Island Hospital, Providence, Rhode Island 02902; Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029; and Liver Research Center Albert Einstein College of Medicine, Bronx, New York 10461
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  • Irmin Sternlieb,

    1. Department of Medicine, Division of Gastroenterology, Brown University and Rhode Island Hospital, Providence, Rhode Island 02902; Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029; and Liver Research Center Albert Einstein College of Medicine, Bronx, New York 10461
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  • Franklin M. Klion,

    1. Department of Medicine, Division of Gastroenterology, Brown University and Rhode Island Hospital, Providence, Rhode Island 02902; Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029; and Liver Research Center Albert Einstein College of Medicine, Bronx, New York 10461
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  • Salvatore Vernace,

    1. Department of Medicine, Division of Gastroenterology, Brown University and Rhode Island Hospital, Providence, Rhode Island 02902; Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029; and Liver Research Center Albert Einstein College of Medicine, Bronx, New York 10461
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  • John Pezzullo

    1. Department of Medicine, Division of Gastroenterology, Brown University and Rhode Island Hospital, Providence, Rhode Island 02902; Department of Medicine, Division of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029; and Liver Research Center Albert Einstein College of Medicine, Bronx, New York 10461
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Abstract

We conducted a prospective clinical trial to assess the relative efficacy and safety of high- vs. low-dose D-penicillamine in patients with primary biliary cirrhosis. Following clinical tests and liver biopsy diagnostic of primary biliary cirrhosis, 56 patients were randomized to receive either 250 or 750 mg D-penicillamine daily. Patients were monitored with clinical tests and annual liver biopsy. Randomization produced two groups without differences in demographic, clinical or histologic characteristics. During the trial, no differences were seen between the mean change in liver test results in patients in either treatment group. The 11% per year rise of bilirubin in the 750 mg dose group during the first 3 years was not significantly different from the 18% per year rise in the 250 mg dose group. No patient showed improvement on liver biopsy although patients on 750 mg D-penicillamine deteriorated more slowly. Side effects, particularly rash and dysgeusia, were more common in the 750 mg dose group. The frequency and severity of side effects were responsible for the early conclusion of our trial. Twenty-six patients experienced side effects necessitating discontinuation of D-penicillamine. No evidence of increased efficacy was demonstrated by high-dose D-penicillamine therapy, and side effects were observed in patients on 250 mg D-penicillamine daily. With the severity of adverse effects and continued progression of disease, D-penicillamine is not a clinically useful therapy in primary biliary cirrhosis.

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