{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T02:02:38Z","timestamp":1788832958241,"version":"build-2803163510"},"reference-count":17,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1985,2]]},"abstract":"<jats:p>One hundred and eighty nine patients with primary biliary cirrhosis were entered into a double blind, placebo controlled randomised trial starting in January 1978 to assess the therapeutic value of d-penicillamine 1200 mg daily. Eighteen of the 98 patients receiving d-penicillamine and 22 of the 91 placebo treated patients died during the study. Thirty six per cent of those on d-penicillamine and 8% of those on placebo were withdrawn from the study. No difference in overall survival was noted between the two groups of patients whether the results were analysed for the entire period of observation or only during the period in which the patients were receiving therapy. The mortality rate of those receiving d-penicillamine in histological stage I to II, however, was one third of that of the placebo group although this difference did not reach statistical significance. Using the occurrence rate ratio as the statistical method of analysis, no effect of d-penicillamine was noted on any clinical, biochemical or histological features examined, except the serum alanine aminotransferase activity which was greater in those on active treatment. In this trial we have been unable to establish any therapeutic benefit from the drug.<\/jats:p>","DOI":"10.1136\/gut.26.2.114","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"114-119","source":"Crossref","is-referenced-by-count":95,"title":["Double blind controlled trial of d-penicillamine in patients with primary biliary cirrhosis."],"prefix":"10.1136","volume":"26","author":[{"given":"J","family":"Neuberger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Portmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Caballeria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Rodes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Ranek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Tygstrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1985,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0016-5085(55)80027-3","article-title":"Effect of steroid therapy on the chemical and laboratory features of primary biliary cirrhosis","volume":"28","author":"Carman, C.T.; Giansiracusa, J.E.","year":"1955","unstructured":"Carman CT, Giansiracusa JE. Effect of steroid therapy on the chemical and laboratory features of primary biliary cirrhosis. Gastroenterology 1955; 28: 193-215.","journal-title":"Gastroenterology"},{"key":"ref_2","first-page":"227","article-title":"The late results of long-term treatment of primary biliary cirrhosis by corticosteroids","volume":"16","author":"Howat, H.T.; Ralston, A.J.; Varley, H.; Wilson, J.A.C.","year":"1966","unstructured":"Howat HT, Ralston AJ, Varley H, Wilson JAC. The late results of long-term treatment of primary biliary cirrhosis by corticosteroids. Rev Int Hepatol 1966; 16: 227-38.","journal-title":"Rev Int Hepatol"},{"key":"ref_3","first-page":"1005","article-title":"Azathioprine in primary biliary cirrhosis. A preliminary report of","volume-title":"an international trial. Gastroenterology 1980","volume":"78","author":"Crowe, J.; Christensen, E.; Smith, M.","unstructured":"Crowe J, Christensen E, Smith M et al. Azathioprine in primary biliary cirrhosis. 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N Engl J Med 1979; 300: 274-8.","journal-title":"N Engl J Med"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/S0021-9258(18)91751-5","article-title":"A defect in the intramolecular and intermolecular cross linking of collagen caused by d-penicillamine","volume":"244","author":"Desmukh, K.; Nimms, M.E.","year":"1969","unstructured":"Desmukh K, Nimms ME. A defect in the intramolecular and intermolecular cross linking of collagen caused by d-penicillamine. J Biol Chem 1969; 244: 1787-95.","journal-title":"J Biol Chem"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S0140-6736(75)91309-4","article-title":"Effect of penicillamine on peripheral blood lymphocytes in rheumatoid arthritis","volume":"1","author":"Brandt, L.; Svensson, B.","year":"1975","unstructured":"Brandt L, Svensson B. Effect of penicillamine on peripheral blood lymphocytes in rheumatoid arthritis. 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New York: Grune and Stratton, 1979: 487-502."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/bjc.1977.1","article-title":"Design and analysis of randomised clinical trial requiring prolonged observation of each patient","volume":"35","author":"Peto, R.; Pike, M.C.; Armitage, P.","year":"1977","unstructured":"Peto R, Pike MC, Armitage P et al. Design and analysis of randomised clinical trial requiring prolonged observation of each patient. II Analysis and example. Br J Cancer 1977; 35: 1-39.","journal-title":"II Analysis and example. Br J Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1056\/NEJM198301063080101","article-title":"The prognostic importance of clinical and histologic features in asymptomatic and symptomatic primary biliary cirrhosis","volume":"308","author":"Roll, JR, Boyer; JL, Barry; D, Klatskin; G.","year":"1983","unstructured":"Roll JR, Boyer JL, Barry D, Klatskin G. 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