{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:02:12Z","timestamp":1790226132258,"version":"4.1.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Autoimmune hepatitis (AIH) requires long-term immunosuppressive therapy, yet the comparative safety profiles of key drugs remain incompletely characterized. The objective of this study was to conduct a systematic evaluation of the adverse drug event (ADE) signals associated with glucocorticoids, specifically dexamethasone, methylprednisolone, and prednisolone, in addition to azathioprine and mycophenolate mofetil, in the treatment of AIH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Disproportionality analysis was performed on ADE reports from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, covering the most recent data available from the first quarter of 2004 through the fourth quarter of 2024. Reporting odds ratios (RORs), proportional reporting ratios (PRRs), and Bayesian confidence propagation neural network metrics were calculated to identify significant ADE signals. Stratified analyses examined demographic and reporting factors influencing ADE patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 720 reports, females accounted for a higher proportion of ADE reports (62.9%). Infections and gastrointestinal disorders were predominant signals across therapies. Glucocorticoid monotherapy showed strong SOC signals for infections, endocrine disorders, and metabolism and nutrition disorders, with opportunistic infections at the PT level. Azathioprine monotherapy exhibited gastrointestinal and neoplasm signals, alongside drug intolerance. Glucocorticoid-azathioprine showed gastrointestinal, infection, and drug intolerance signals; glucocorticoid-mycophenolate mofetil linked to infections. Mycophenolate mofetil monotherapy exhibited medication management failures. Stratified analyses revealed higher ADE reporting frequencies in females, patients \u226565 years, and differential reporting patterns by occupation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identified distinct ADE profiles for AIH therapies. These findings underscore the need for personalized monitoring strategies to mitigate treatment-specific ADEs in AIH management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1889345","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:37:33Z","timestamp":1790224653000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Detection of adverse event signals associated with key immunosuppressants for autoimmune hepatitis: insights from the food and drug administration adverse event reporting system database"],"prefix":"10.3389","volume":"17","author":[{"given":"Luyuan","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Hebei Medical University Third Hospital","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yize","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Burn and Plastic Surgery Department, Hebei Medical University Third Hospital","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hebei Medical University Third Hospital","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hebei Medical University Third Hospital","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hebei Medical University Third Hospital","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hebei Medical University Third Hospital","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Allergy Department, Hebei Medical University First Hospital","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hebei Medical University Third Hospital","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e13178","DOI":"10.1111\/tid.13178","article-title":"Treatment of latent TB infection and the risk of tuberculosis after solid organ transplantation: comprehensive review","volume":"21","author":"Abad","year":"2019","journal-title":"Transpl. Infect. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1186\/s12876-025-04206-1","article-title":"Mycophenolate mofetil versus azathioprine as a first-line treatment for autoimmune hepatitis: a comparative systematic review and meta-analysis","volume":"25","author":"Ali","year":"2025","journal-title":"BMC Gastroenterol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3285","DOI":"10.1007\/s00210-025-04721-8","article-title":"Biological sex differences in pharmacokinetics and adverse drug reactions","volume":"399","author":"Aljohmani","year":"2026","journal-title":"Naunyn Schmiedeb. Arch. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/s41397-021-00255-3","article-title":"Association of ITPA gene polymorphisms with adverse effects of AZA\/6-MP administration: a systematic review and meta-analysis","volume":"22","author":"Barba","year":"2022","journal-title":"Pharmacogenomics J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1007\/s12016-023-08963-3","article-title":"Perspectives on mycophenolate mofetil in the management of autoimmunity","volume":"65","author":"Bhat","year":"2023","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.phrs.2018.07.021","article-title":"Diagnostic accuracy of NUDT15 gene variants for thiopurine-induced leukopenia: a systematic review and meta-analysis","volume":"135","author":"Cargnin","year":"2018","journal-title":"Pharmacol. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1007\/s12325-022-02067-8","article-title":"Genotype-guided prescription of azathioprine reduces the incidence of adverse drug reactions in TPMT intermediate metabolizers to a similar incidence as normal metabolizers","volume":"39","author":"Casaj\u00fas","year":"2022","journal-title":"Adv. Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e37","DOI":"10.1093\/cid\/ciad474","article-title":"Unintended consequences: risk of opportunistic infections associated with long-term glucocorticoid therapies in adults","volume":"78","author":"Chastain","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1080\/17512433.2025.2465425","article-title":"Effectiveness and safety of thiopurines in inflammatory bowel disease patients with NUDT15 polymorphism: a real-world retrospective study","volume":"18","author":"Chatterjee","year":"2025","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"4913","DOI":"10.2147\/idr.s414763","article-title":"Co-Infection Talaromyces marneffei and Pneumocystis jirovecii in a patient with systemic lupus erythematosus","volume":"16","author":"Chen","year":"2023","journal-title":"Infect. Drug Resist"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e46512","DOI":"10.1097\/md.0000000000046512","article-title":"Closed-loop medication safety management reduces inappropriate medication in elderly patients with rheumatic and immunologic diseases","volume":"105","author":"Chen","year":"2026","journal-title":"Med. Baltim."},{"key":"B12","doi-asserted-by":"publisher","first-page":"100601","DOI":"10.1016\/j.jhepr.2022.100601","article-title":"Long-term results of mycophenolate mofetil vs. azathioprine use in individuals with autoimmune hepatitis","volume":"4","author":"Dalekos","year":"2022","journal-title":"JHEP Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.jhep.2025.03.017","article-title":"EASL Clinical Practice Guidelines on the management of autoimmune hepatitis","volume":"83","author":"Dalekos","year":"2025","journal-title":"J Hepatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"6757524","DOI":"10.1155\/2019\/6757524","article-title":"Gastrointestinal tract disorders in older age","volume":"2019","author":"Dumic","year":"2019","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1111\/apt.14968","article-title":"Inequity of care provision and outcome disparity in autoimmune hepatitis in the United Kingdom","volume":"48","author":"Dyson","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e13200","DOI":"10.1111\/tid.13200","article-title":"Outcomes of solid organ transplant recipients with invasive aspergillosis and other mold infections","volume":"22","author":"Farges","year":"2020","journal-title":"Transpl. Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"500","DOI":"10.3390\/life14040500","article-title":"Are gender differences important for autoimmune liver diseases?","volume":"14","author":"Floreani","year":"2024","journal-title":"Life (Basel)"},{"key":"B18","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.jhep.2020.07.032","article-title":"Update of the simplified criteria for autoimmune hepatitis: evaluation of the methodology for immunoserological testing","volume":"74","author":"Galaski","year":"2021","journal-title":"J. Hepatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.cld.2023.07.001","article-title":"Treatment of autoimmune hepatitis","volume":"28","author":"Goel","year":"2024","journal-title":"Clin. Liver Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3350\/cmh.2020.0189","article-title":"Recent updates on the management of autoimmune hepatitis","volume":"27","author":"Komori","year":"2021","journal-title":"Clin. Mol. Hepatol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e0006019","DOI":"10.1128\/cmr.00060-19","article-title":"Human listeriosis","volume":"36","author":"Koopmans","year":"2023","journal-title":"Clin. Microbiol. Rev."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e0334500","DOI":"10.1371\/journal.pone.0334500","article-title":"Mining and analysis of reported ARDS population in FAERS database","volume":"20","author":"Lai","year":"2025","journal-title":"PLoS One"},{"key":"B23","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.cgh.2020.05.061","article-title":"Trends in incidence of autoimmune liver diseases and increasing incidence of autoimmune hepatitis","volume":"19","author":"Lamba","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"493","DOI":"10.14218\/jcth.2025.00008","article-title":"The role of novel immunomodulators in the treatment of autoimmune hepatitis","volume":"13","author":"Li","year":"2025","journal-title":"J. Clin. Transl. Hepatol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1111\/j.1532-5415.1985.tb07117.x","article-title":"Longitudinal studies on the rate of decline in renal function with age","volume":"33","author":"Lindeman","year":"1985","journal-title":"J. Am. Geriatr. Soc."},{"key":"B26","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1002\/hep.31065","article-title":"Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American association for the study of liver diseases","volume":"72","author":"Mack","year":"2020","journal-title":"Hepatology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1443794","DOI":"10.3389\/fphar.2024.1443794","article-title":"In vitro mechanistic study on mycophenolate mofetil drug interactions: effect of prednisone, cyclosporine, and others","volume":"15","author":"Mao","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e070201","DOI":"10.1136\/bmj-2022-070201","article-title":"Diagnosis and management of autoimmune hepatitis","volume":"380","author":"Muratori","year":"2023","journal-title":"Bmj"},{"key":"B29","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1517\/14740338.2016.1140743","article-title":"Long-term side effects of glucocorticoids","volume":"15","author":"Oray","year":"2016","journal-title":"Expert Opin. Drug Saf."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1016\/j.cgh.2018.12.035","article-title":"Predniso(lo)ne dosage and chance of remission in patients with autoimmune hepatitis","volume":"17","author":"Pape","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"7200","DOI":"10.3390\/ijms26157200","article-title":"ER\u03b136 promotes MDR1-Mediated adriamycin resistance via non-genomic signaling in triple-negative breast cancer","volume":"26","author":"Poyonov","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e0458","DOI":"10.1097\/hc9.0000000000000458","article-title":"Autoimmune hepatitis: current and future therapies","volume":"8","author":"Reau","year":"2024","journal-title":"Hepatol Commun."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1007\/s15010-024-02314-w","article-title":"Epidemiology and risk factors of community-acquired pneumonia in patients with different causes of immunosuppression","volume":"52","author":"Reichel","year":"2024","journal-title":"Infection"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.3390\/cells14171363","article-title":"Molecular aspects of geriatric pharmacotherapy","volume":"14","author":"Rzeczycki","year":"2025","journal-title":"Cells"},{"key":"B35","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1111\/apt.15157","article-title":"Systematic review with meta-analysis: mycophenolate mofetil as a second-line therapy for autoimmune hepatitis","volume":"49","author":"Santiago","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2687","DOI":"10.1111\/liv.16035","article-title":"Unmet needs in autoimmune hepatitis: results of the prospective multicentre european reference network registry (R-LIVER)","volume":"44","author":"Schregel","year":"2024","journal-title":"Liver Int."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1016\/j.ekir.2024.04.043","article-title":"Infectious disease prophylaxis during and after immunosuppressive therapy","volume":"9","author":"Schweitzer","year":"2024","journal-title":"Kidney Int. Rep."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1545373","DOI":"10.3389\/fneph.2025.1545373","article-title":"Treatment burden in glomerular diseases: advances and challenges in immunosuppressive therapy","volume":"5","author":"Shankar","year":"2025","journal-title":"Front. Nephrol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cld.2023.06.002","article-title":"Autoimmune hepatitis: epidemiology, subtypes, and presentation","volume":"28","author":"Shiffman","year":"2024","journal-title":"Clin. Liver Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e41","DOI":"10.1016\/j.jhep.2024.02.022","article-title":"Autoimmune hepatitis: mycophenolate mofetil vs. azathioprine as first-line therapy","volume":"81","author":"\u015eim\u015fek","year":"2024","journal-title":"J. Hepatol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e12745","DOI":"10.1111\/tid.12745","article-title":"Legionnaires' disease in transplant recipients: a 15-year retrospective study in a tertiary referral center","volume":"19","author":"Sivagnanam","year":"2017","journal-title":"Transpl. Infect. Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.jhep.2023.11.032","article-title":"An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis","volume":"80","author":"Snijders","year":"2024","journal-title":"J. Hepatol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"105280","DOI":"10.1016\/j.ejps.2020.105280","article-title":"Impact of gastrointestinal physiology on drug absorption in special populations--An UNGAP review","volume":"147","author":"Stillhart","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1111\/apt.15528","article-title":"Adverse events related to low dose corticosteroids in autoimmune hepatitis","volume":"50","author":"van den Brand","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1052692","DOI":"10.3389\/fimmu.2022.1052692","article-title":"PROS1 shapes the immune-suppressive tumor microenvironment and predicts poor prognosis in glioma","volume":"13","author":"Wang","year":"","journal-title":"Front. Immunol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1021\/acs.molpharmaceut.1c00792","article-title":"In Vitro predictive dissolution test should be developed and recommended as a bioequivalence standard for the immediate-release solid oral dosage forms of the highly variable mycophenolate mofetil","volume":"19","author":"Wang","year":"","journal-title":"Mol. Pharm."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1002628","DOI":"10.3389\/fphar.2022.1002628","article-title":"Population pharmacokinetics of mycophenolate mofetil in pediatric patients early after liver transplantation","volume":"13","author":"Wei","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.therap.2023.11.003","article-title":"Drug-induced tumoral disease: a global pharmacovigilance database analysis","volume":"79","author":"Zelmat","year":"2024","journal-title":"Therapie"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1820377","DOI":"10.3389\/fmed.2026.1820377","article-title":"Detection of drug-induced acute respiratory distress syndrome risk signals in FAERS: a real-world pharmacovigilance study","volume":"13","author":"Zhao","year":"2026","journal-title":"Front. Med. (Lausanne)"},{"key":"B50","doi-asserted-by":"publisher","first-page":"6348","DOI":"10.3748\/wjg.v27.i38.6348","article-title":"Biomarkers for gastrointestinal adverse events related to thiopurine therapy","volume":"27","author":"Zudeh","year":"2021","journal-title":"World J. Gastroenterol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1889345\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:37:47Z","timestamp":1790224667000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1889345\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":50,"alternative-id":["10.3389\/fphar.2026.1889345"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1889345","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"article-number":"1889345"}}