{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T10:22:03Z","timestamp":1779358923484,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,1,24]],"date-time":"2013-01-24T00:00:00Z","timestamp":1358985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ten percent of patients with autoimmune hepatitis (<jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content>) are nonresponsive or intolerant to thiopurine therapy. A skewed metabolism, leading to the preferential generation of (hepato)toxic thiopurine metabolites (6\u2010<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>s) instead of the metabolic active 6\u2010tioguanine (thioguanine) nucleotides (6\u2010<jats:styled-content style=\"fixed-case\">TGN<\/jats:styled-content>s), may explain this unfavourable outcome. Co\u2010administration of allopurinol to low\u2010dose thiopurine therapy may effectively revert this deviant metabolism, as has been shown in inflammatory bowel disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To describe the effect of adding allopurinol to low\u2010dose thiopurine therapy in patients with <jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content> with intolerance or nonresponse to normal thiopurine dosages due to a skewed metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We describe the clinical efficacy and tolerability of allopurinol\u2013thiopurine combination therapy with allopurinol 100\u00a0mg and low\u2010dose thiopurine (25\u201333% of the original dosage) in eight <jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content> patients with a skewed thiopurine metabolism. Patients were switched because of dose\u2010limiting intolerance (<jats:italic>n<\/jats:italic>\u00a0=\u00a03), nonresponse (<jats:italic>n<\/jats:italic>\u00a0=\u00a03) or loss of response (<jats:italic>n<\/jats:italic>\u00a0=\u00a02) to conventional thiopurine treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All eight patients showed biochemical improvement with a reduction in median alanine aminotransferase (<jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content>) levels of 62\u00a0U\/L at start to 35\u00a0U\/L at 1\u00a0month (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.03). This clinical benefit was sustained in seven patients. Allopurinol\u2013thiopurine combination therapy effectively bypassed thiopurine side effects in four of five patients. Median 6\u2010tioguanine nucleotides levels increased from 100 to 200\u00a0pmol\/8\u00a0\u00d7\u00a010<jats:sup>8<\/jats:sup> red blood cells (<jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content>) at 3\u00a0months (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.04). Median 6\u2010<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content> levels decreased in all patients from 6090 to 175\u00a0pmol\/8\u00a0\u00d7\u00a010<jats:sup>8<\/jats:sup> <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content> (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Allopurinol safely and effectively optimises thiopurine therapy in patients with autoimmune hepatitis with intolerance and\/or nonresponse due to an unfavourable thiopurine metabolism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.12223","type":"journal-article","created":{"date-parts":[[2013,1,24]],"date-time":"2013-01-24T17:34:19Z","timestamp":1359048859000},"page":"640-646","source":"Crossref","is-referenced-by-count":50,"title":["Allopurinol safely and effectively optimises thiopurine metabolites in patients with autoimmune hepatitis"],"prefix":"10.1111","volume":"37","author":[{"given":"Y. S.","family":"de Boer","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology VU University Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. M. F.","family":"van Gerven","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology VU University Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. K. H.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology VU University Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. J. J.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology VU University Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Bouma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology VU University Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. M. J.","family":"van Nieuwkerk","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology VU University Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,1,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23584"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.235259"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpgasthep1000"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(92)80347-S"},{"key":"e_1_2_7_6_1","first-page":"601","article-title":"Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase","volume":"29","author":"Weinshilboum R","year":"2001","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70140-5"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2005.02583.x"},{"key":"e_1_2_7_9_1","article-title":"Safety and effectiveness of long\u2010term allopurinol\u2010thiopurine maintenance treatment in inflammatory bowel disease","author":"Hoentjen F","year":"2012","journal-title":"Inflamm Bowel Dis"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2009.04221.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1093\/clinchem\/44.3.551","article-title":"Simultaneous determination of 6\u2010thioguanine and methyl 6\u2010mercaptopurine nucleotides of azathioprine in red blood cells by HPLC","volume":"44","author":"Dervieux T","year":"1998","journal-title":"Clin Chem"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(87)80340-7"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1373\/49.2.260"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(99)80297-9"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000116934"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25760"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-012-2151-2"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2008.02180.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04727.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.12.032"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.7.2.145"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e3181e44244"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapt.12223","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.12223","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T17:00:59Z","timestamp":1700672459000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.12223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,24]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1111\/apt.12223"],"URL":"https:\/\/doi.org\/10.1111\/apt.12223","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,24]]}}}