{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T09:44:45Z","timestamp":1785577485069,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Turkish Society of Gastroenterology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Azathioprine (AZA)-associated acute pancreatitis (AP) and gastrointestinal intolerance (GI-INT) are major causes of drug discontinuation in inflammatory bowel disease (IBD). This study compared HLA alleles, demographics, and clinical variables between AZA-AP and AZA-GI-INT. Methods: Data from five IBD centers included control (n = 88), AZA-AP (n = 44), and GI-INT (n = 44) groups. AP was defined by the Atlanta criteria, and GI-INT as acute dyspeptic symptoms related to AZA that resolved after withdrawal. Demographics, disease features, and HLA-DQA1\/DRB1 alleles were assessed for associations. Results: Among 176 patients, female sex was more frequent in AZA-AP and GI-INT than controls (p = 0.018, p &lt; 0.001). AZA-AP patients were older at diagnosis vs. controls (p = 0.016) but not vs. GI-INT (p = 0.15). Smoking and alcohol were more common in AZA-AP. The median onset of AP was four weeks, with 91% occurring within three months. GI-INT occurred rapidly, with a median of one day and a maximum of three days after the first dose. HLA-DQA1\/DRB1 positivity was comparable in GI-INT and controls (9.2% vs. 14.8%, p = 0.42) but higher in AZA-AP (27.3% vs. 14.8%, p = 0.08). Regression identified female sex, smoking, alcohol, budesonide, and HLA-DQA1\/DRB1 positivity (OR 3.01, 95% CI 1.004\u20139.058; p = 0.049) as independent risk factors for AZA-AP. Conclusions: AZA-AP, but not GI-INT, appears genetically influenced, with HLA-DQA1\/DRB1 association extending across populations. In IBD, AZA-AP usually emerges within three months and is linked to female sex, smoking, alcohol, and budesonide. GI-INT typically develops within hours to three days of initiation. These findings support AZA-AP and GI-INT as distinct idiosyncratic entities shaped by genetic, metabolic, and sensitivity factors.<\/jats:p>","DOI":"10.3390\/jcm14238539","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:20:29Z","timestamp":1765210829000},"page":"8539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparison of Azathioprine-Induced Pancreatitis and Gastrointestinal Intolerance in IBD: Role of Demographics, Clinical Variables, and HLA DQA1\/DRB1 Alleles"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3008-1940","authenticated-orcid":false,"given":"Tugce","family":"Eskazan","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, \u0130stanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8661-5791","authenticated-orcid":false,"given":"Oguz Kagan","family":"Bakkaloglu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, \u0130stanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8873-7426","authenticated-orcid":false,"given":"Murat","family":"Toruner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Ankara University Faculty of Medicine, Ankara 06620, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0042-9256","authenticated-orcid":false,"given":"Haluk Tarik","family":"Kani","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Marmara University Faculty of Medicine, \u0130stanbul 34722, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2203-4255","authenticated-orcid":false,"given":"Bilger","family":"Cavus","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, \u0130stanbul University Faculty of Medicine, \u0130stanbul 34093, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9625-1344","authenticated-orcid":false,"given":"Volkan","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Ankara University Faculty of Medicine, Ankara 06620, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8870-2450","authenticated-orcid":false,"given":"Nalan Gulsen","family":"Unal","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Ege University Faculty of Medicine, \u0130zmir 35040, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9695-9416","authenticated-orcid":false,"given":"Ozlen","family":"Atug","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Marmara University Faculty of Medicine, \u0130stanbul 34722, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burhan","family":"Cagcag","sequence":"additional","affiliation":[{"name":"HLA Tissue Typing Laboratory, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, \u0130stanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4354-2489","authenticated-orcid":false,"given":"Mehtap","family":"Dogruel","sequence":"additional","affiliation":[{"name":"HLA Tissue Typing Laboratory, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, \u0130stanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5133-4532","authenticated-orcid":false,"given":"Erkan","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"HLA Tissue Typing Laboratory, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, \u0130stanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7498-141X","authenticated-orcid":false,"given":"Filiz","family":"Akyuz","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, \u0130stanbul University Faculty of Medicine, \u0130stanbul 34093, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9460-1469","authenticated-orcid":false,"given":"Yusuf Ziya","family":"Erzin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, \u0130stanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8385-9253","authenticated-orcid":false,"given":"Ali Ibrahim","family":"Hatemi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, \u0130stanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aykut Ferhat","family":"Celik","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, \u0130stanbul 34098, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1097\/MIB.0b013e318281f28f","article-title":"Safety of Thiopurine Therapy in Inflammatory Bowel Disease: Long-term follow-up study of 3931 patients","volume":"19","author":"Chaparro","year":"2013","journal-title":"Inflamm. 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