{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:11:19Z","timestamp":1790428279893,"version":"4.1.0"},"reference-count":73,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":9984,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1988,5]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Primary biliary cirrhosis is a chronic, progressive, cholestatic liver disease thought to be related to abnormalities in immune regulation. The disease is associated with granulomatous bile duct destruction, cholestasis, hepatic copper overloading and the development of hepatic fibrosis or cirrhosis or both. There have been numerous therapeutic trials evaluating immunosuppres-sive, antifibrotic and cupruretic agents. Prednisolone, D-penicillamine, azathioprine, colchicine and chloram-bucil have been evaluated in controlled clinical trials, and biochemical improvement of liver function has been noted with all of the agents, except D-penicillamine. Improved survival has also been reported in patients treated long-term with azathioprine and colchicine. However, none of the therapeutic agents has been demonstrated to halt histologic progression of the disease or to induce a complete clinical, biochemical and histologic remission as has been reported in patients with autoimmune chronic active hepatitis treated with corticoste-roids. Many of the trials did not use a double-blind design, failed to use the \u201cintent to treat\u201d rule or failed to define an objective time to analyze results. Many of the studies involved small numbers of patients with short-term follow-up and thus potentially were inadequate to appreciate drug effects that might be of clinical benefit. Currently, there is no totally effective therapy for primary biliary cirrhosis. We believe that well-designed clinical trials can provide important information to better understand this disease until a totally effective therapy is available. New clinical trials should use well-established methodologic guidelines in study design and well-accepted statistical standards in the analysis and interpretation of results.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840080339","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T21:24:49Z","timestamp":1172957089000},"page":"668-676","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":51,"title":["Clinical and statistical analyses of new and evolving therapies for primary biliary cirrhosis"],"prefix":"10.1097","volume":"8","author":[{"given":"Russell H.","family":"Wiesner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia M.","family":"Grambsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith D.","family":"Lindor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurgen","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolland E.","family":"Dickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840080339-BIB1","first-page":"487","volume":"6","author":"Dickson","year":"1979","journal-title":"Prog Liver Dis"},{"key":"10.1002\/hep.1840080339-BIB2","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1056\/NEJM198702263160907","volume":"316","author":"Kaplan","year":"1987","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840080339-BIB3","doi-asserted-by":"crossref","first-page":"500","DOI":"10.7326\/0003-4819-99-4-500","volume":"99","author":"James","year":"1983","journal-title":"Ann Intern Med"},{"key":"10.1002\/hep.1840080339-BIB4","first-page":"553","volume":"55","author":"Bernstein","year":"1984","journal-title":"Clin Exp Immunol"},{"key":"10.1002\/hep.1840080339-BIB5","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/0016-5085(80)90136-5","volume":"79","author":"James","year":"1980","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB6","first-page":"297","volume":"61","author":"Nouri-Aria","year":"1985","journal-title":"Clin Exp Immunol"},{"key":"10.1002\/hep.1840080339-BIB7","first-page":"636","volume":"99","author":"Lindgren","year":"1982","journal-title":"J Lab Clin Med"},{"key":"10.1002\/hep.1840080339-BIB8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/hep.1840040102","volume":"4","author":"Lindgren","year":"1984","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840080339-BIB9","first-page":"432","volume":"105","author":"Lindgren","year":"1985","journal-title":"J Lab Clin Med"},{"key":"10.1002\/hep.1840080339-BIB10","first-page":"427","volume":"88","author":"Potter","year":"1976","journal-title":"J Lab Clin Med"},{"key":"10.1002\/hep.1840080339-BIB11","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1056\/NEJM197802022980502","volume":"298","author":"Wands","year":"1978","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840080339-BIB12","first-page":"19","volume":"34","author":"Gupta","year":"1978","journal-title":"Clin Exp Immunol"},{"key":"10.1002\/hep.1840080339-BIB13","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/S0016-5085(82)80206-0","volume":"83","author":"Goldberg","year":"1982","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB14","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/BF01308306","volume":"25","author":"Zetterman","year":"1980","journal-title":"Dis Sci"},{"key":"10.1002\/hep.1840080339-BIB15","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1172\/JCI109982","volume":"66","author":"James","year":"1980","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.1840080339-BIB16","first-page":"1741","volume":"90","author":"Lindor","year":"1986","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB17","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0098-2997(85)90009-3","volume":"8","author":"McFarlane","year":"1985","journal-title":"Molec Aspects Med"},{"key":"10.1002\/hep.1840080339-BIB18","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/BF00929460","volume":"5","author":"James","year":"1985","journal-title":"J Clin Immunol"},{"key":"10.1002\/hep.1840080339-BIB19","first-page":"351","volume":"47","author":"Bhan","year":"1982","journal-title":"Clin Exp Immunol"},{"key":"10.1002\/hep.1840080339-BIB20","first-page":"365","volume":"57","author":"Culp","year":"1982","journal-title":"Mayo Clin Proc"},{"key":"10.1002\/hep.1840080339-BIB21","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/S0016-5085(19)30497-4","volume":"78","author":"Crowe","year":"1980","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB22","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1136\/ard.37.1.42","volume":"37","author":"Clarke","year":"1978","journal-title":"Ann Rheum Dis"},{"key":"10.1002\/hep.1840080339-BIB23","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/0016-5085(85)90001-0","volume":"88","author":"Portmann","year":"1985","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB24","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/BF00915293","volume":"4","author":"Si","year":"1984","journal-title":"J Clin Immunol"},{"key":"10.1002\/hep.1840080339-BIB25","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/S0140-6736(84)91108-5","volume":"2","author":"Ballardini","year":"1984","journal-title":"Lancet"},{"key":"10.1002\/hep.1840080339-BIB26","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/S0046-8177(81)80081-0","volume":"12","author":"Bernuau","year":"1981","journal-title":"Hum Pathol"},{"key":"10.1002\/hep.1840080339-BIB27","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0016-5085(85)90325-7","volume":"89","author":"Beswick","year":"1985","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB28","doi-asserted-by":"crossref","first-page":"485","DOI":"10.7326\/0003-4819-106-3-485","volume":"106","author":"Mulrow","year":"1987","journal-title":"Ann Intern Med"},{"key":"10.1002\/hep.1840080339-BIB29","volume-title":"Fundamentals of clinical trials","author":"Friedman","year":"1985","unstructured":", . Fundamentals of clinical trials, 2nd ed. Littleton, Massachusetts: PSG Publishing Company, 1985."},{"key":"10.1002\/hep.1840080339-BIB30","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/bjc.1976.220","volume":"34","author":"Peto","year":"1976","journal-title":"Br J Cancer"},{"key":"10.1002\/hep.1840080339-BIB31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/bjc.1977.1","volume":"35","author":"Peto","year":"1977","journal-title":"Br J Cancer"},{"key":"10.1002\/hep.1840080339-BIB32","first-page":"909","volume":"23","author":"Bassendine","year":"1982","journal-title":"Gut"},{"key":"10.1002\/hep.1840080339-BIB33","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1002\/hep.1840050613","volume":"5","author":"Bodenheimer","year":"1985","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840080339-BIB34","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/S0140-6736(81)92456-9","volume":"1","author":"Epstein","year":"1981","journal-title":"Lancet"},{"key":"10.1002\/hep.1840080339-BIB35","doi-asserted-by":"crossref","first-page":"499","DOI":"10.2307\/2531021","volume":"39","author":"Schoenfeld","year":"1983","journal-title":"Biometrics"},{"key":"10.1002\/hep.1840080339-BIB36","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0197-2456(81)90001-5","volume":"2","author":"Lachin","year":"1981","journal-title":"Controlled Clin Trials"},{"key":"10.1002\/hep.1840080339-BIB37","first-page":"227","volume":"16","author":"Howat","year":"1966","journal-title":"Rev Int Hepatol"},{"key":"10.1002\/hep.1840080339-BIB38","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0016-5085(55)80027-3","volume":"28","author":"Carman","year":"1955","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB39","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1002\/hep.1840060609","volume":"6","author":"Mitchison","year":"1986","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840080339-BIB40","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1001\/jama.1964.03070100042008","volume":"189","author":"Sternlieb","year":"1964","journal-title":"JAMA"},{"key":"10.1002\/hep.1840080339-BIB41","doi-asserted-by":"crossref","first-page":"57","DOI":"10.7326\/0003-4819-75-1-57","volume":"75","author":"Deiss","year":"1971","journal-title":"Ann Intern Med"},{"key":"10.1002\/hep.1840080339-BIB42","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/newbio240220a0","volume":"240","author":"Nimni","year":"1972","journal-title":"Nature"},{"key":"10.1002\/hep.1840080339-BIB43","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1056\/NEJM197902083000602","volume":"300","author":"Epstein","year":"1979","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840080339-BIB44","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1172\/JCI109759","volume":"65","author":"Lipsky","year":"1980","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.1840080339-BIB45","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1136\/gut.26.2.114","volume":"26","author":"Neuberger","year":"1985","journal-title":"Gut"},{"key":"10.1002\/hep.1840080339-BIB46","first-page":"1032","volume":"4","author":"Epstein","year":"1984","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840080339-BIB47","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1056\/NEJM198504183121602","volume":"312","author":"Dickson","year":"1985","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840080339-BIB48","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1056\/NEJM198202113060602","volume":"306","author":"Matloff","year":"1982","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840080339-BIB49","first-page":"919","volume":"21","author":"Triger","year":"1980","journal-title":"Gut"},{"key":"10.1002\/hep.1840080339-BIB50","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/j.1600-0676.1983.tb00887.x","volume":"3","author":"Taal","year":"1983","journal-title":"Liver"},{"key":"10.1002\/hep.1840080339-BIB51","first-page":"49","volume":"1","author":"Epstein","year":"1985","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840080339-BIB52","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/S0016-5085(76)80250-8","volume":"70","author":"Heathcote","year":"1976","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB53","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/0016-5085(80)90784-2","volume":"78","author":"Crowe","year":"1980","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB54","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/0016-5085(85)90213-6","volume":"89","author":"Christensen","year":"1985","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB55","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1073\/pnas.69.4.892","volume":"69","author":"Diegelmann","year":"1972","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/hep.1840080339-BIB56","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/1523-1747.ep12530243","volume":"79","author":"Bauer","year":"1982","journal-title":"J Invest Dermatol"},{"key":"10.1002\/hep.1840080339-BIB57","first-page":"99","volume":"50","author":"Ilfeld","year":"1982","journal-title":"Clin Exp Immunol"},{"key":"10.1002\/hep.1840080339-BIB58","first-page":"438","volume":"57","author":"Ilfeld","year":"1984","journal-title":"Clin Exp Immunol"},{"key":"10.1002\/hep.1840080339-BIB59","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1002\/art.1780180729","volume":"18","author":"Malawista","year":"1975","journal-title":"Arthritis Rheum"},{"key":"10.1002\/hep.1840080339-BIB60","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/0016-5085(79)90018-0","volume":"77","author":"Kershenobich","year":"1979","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB61","first-page":"1309","volume":"78","author":"Koldinger","year":"1980","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB62","first-page":"1022","volume":"4","author":"Warnes","year":"1984","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840080339-BIB63","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00432479","volume":"379","author":"Ludwig","year":"1978","journal-title":"Virchows Arch (Pathol Anat)"},{"key":"10.1002\/hep.1840080339-BIB64","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1056\/NEJM198612043152304","volume":"315","author":"Kaplan","year":"1986","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840080339-BIB65","first-page":"1172","volume":"6","author":"Bodenheimer","year":"1986","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840080339-BIB66","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1056\/NEJM198004243021701","volume":"302","author":"Williams","year":"1980","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840080339-BIB67","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/0016-5085(86)90183-6","volume":"91","author":"Hoofnagle","year":"1986","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB68","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1056\/NEJM198102193040801","volume":"304","author":"Berk","year":"1981","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840080339-BIB69","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1001\/archinte.1979.03630410067021","volume":"139","author":"Gruenwald","year":"1979","journal-title":"Arch Intern Med"},{"key":"10.1002\/hep.1840080339-BIB70","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S0016-5085(19)33223-8","volume":"63","author":"Soloway","year":"1972","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080339-BIB71","first-page":"1020","volume":"5","author":"Wiesner","year":"1985","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840080339-BIB72","first-page":"1025","volume":"7","author":"Balasubramaniam","year":"1987","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840080339-BIB73","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/S0140-6736(87)91610-2","volume":"1","author":"Poupon","year":"1987","journal-title":"Lancet"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.1840080339","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-198805000-00038","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T18:19:17Z","timestamp":1742840357000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-198805000-00038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1988,5]]},"references-count":73,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1988]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.1840080339","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[1988,5]]}}}