{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:33:00Z","timestamp":1790836380653,"version":"4.1.0"},"reference-count":91,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Autoimmune hepatitis (AIH) remains difficult to study mechanistically in patients because disease initiation is rarely observed directly, the relevant autoantigens differ across subsets, and clinically meaningful outcomes such as chronic inflammation, fibrosis, relapse, and treatment response evolve over time. Animal models therefore remain indispensable. At the same time, the field has become increasingly heterogeneous. Acute immune\u2010mediated hepatitis systems, especially concanavalin A (ConA), dominate the recent literature because they are rapid, inexpensive, and experimentally tractable. However, ConA\u2010induced hepatitis is not an antigen\u2010driven autoimmune response and is better interpreted as acute bystander immune\u2010mediated liver injury than as a stand\u2010alone model of chronic AIH. In contrast, antigen\u2010driven adenoviral models based on cytochrome P450 2D6 (CYP2D6) or formiminotransferase cyclodeaminase (FTCD), as well as genetically predisposed or spontaneous tolerance\u2010defect models, provide stronger insight into loss of hepatic tolerance, chronicity, fibrosis, and the interaction between antigenic context and host susceptibility. This review proposes a pragmatic framework for evaluating AIH models on the basis of face validity, construct validity, predictive validity, chronicity, host susceptibility, and mechanistic fitness for a specific biological question. Using that framework, we classify current models into acute surrogate models, immunization\u2010 and xenoantigen\u2010based systems, adenoviral antigen\u2010driven chronic models, spontaneous and genetically predisposed models, transgenic or neoantigen\u2010driven tolerance models, and humanized or microbiota\u2010sensitive hybrid systems. We then synthesize what these systems have taught the field about central and peripheral tolerance, MHC and non\u2010MHC genetic susceptibility, sex\u2010 and age\u2010related disease context, CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell biology, B\u2010cell function, regulatory T\u2010cell instability, impaired suppressive function, defective IL\u20102\u2010dependent regulation, macrophage and innate lymphocyte participation, cell\u2010death programmes, and gut\u2010liver or liver\u2010microbiome interactions. A central conclusion emerges: AIH models are complementary tools with markedly different levels of disease fidelity, and they should not be treated as interchangeable. Acute systems remain useful for effector\u2010phase biology and first\u2010pass intervention studies, but the strongest translational inferences for chronic AIH come from antigen\u2010defined chronic models and selected tolerance\u2010defect systems. Future progress will depend on better benchmarking across models, stronger alignment with human immune profiling and ex\u00a0vivo validation platforms, and wider use of tolerance\u2010restoring rather than purely anti\u2010inflammatory therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1111\/liv.70797","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:12:28Z","timestamp":1784023948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Experimental Models of Autoimmune Hepatitis: Disease Fidelity and Translational Relevance"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0051-2044","authenticated-orcid":false,"given":"Laura Elisa","family":"Buitrago\u2010Molina","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Disease and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2827-7787","authenticated-orcid":false,"given":"Matthias","family":"Hardtke\u2010Wolenski","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Disease and Endocrinology Hannover Medical School  Hannover Germany"},{"name":"Institute of Medical Microbiology University Hospital Essen, University Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.05.017"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000341114"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000282067"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2005.11.001"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23536"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2016.12.001"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13665"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12242854"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.1117"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxres\/tfaf036"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840050511"},{"issue":"2","key":"e_1_2_16_13_1","first-page":"276","article-title":"Adoptive Transfer of Experimental Autoimmune Hepatitis in Mice\u2013Cellular Interaction Between Donor and Recipient Mice","volume":"73","author":"Ogawa M.","year":"1988","journal-title":"Clinical and Experimental Immunology"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6551069"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2023.10.001"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20109"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2021.10.006"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071859"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.11.001"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2013.05.001"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2016.02.007"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26380"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14296"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27998"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12843"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65414"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27639"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.6077"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.01.002"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1253649"},{"key":"e_1_2_16_31_1","doi-asserted-by":"crossref","unstructured":"K.Hao K. 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