{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T07:45:24Z","timestamp":1785743124955,"version":"3.56.0"},"reference-count":173,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474179"],"award-info":[{"award-number":["82474179"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medicinal Research Reviews"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Immune checkpoint inhibitors and adoptive cell therapies have revolutionized cancer treatment, yet their success is accompanied by immune\u2010related hepatotoxicity that can range from asymptomatic enzyme elevation to life\u2010threatening liver failure. Unlike conventional drug\u2010induced liver injury, immune\u2010mediated hepatotoxicity arises from complex, therapy\u2010specific mechanisms that remain incompletely understood, creating critical knowledge gaps in risk prediction and prevention. This review incorporates current evidence on the clinical presentation, mechanistic pathways, and risk factors underlying hepatotoxicity across major immune and cell therapy platforms, with emphasis on translating mechanistic insights into actionable management strategies. We systematically examine hepatotoxicity patterns for immune checkpoint inhibitors, CAR\u2010T cell therapies, bispecific T\u2010cell engagers, and tumor\u2010infiltrating lymphocyte therapy, integrating clinical trial data, real\u2010world evidence, and mechanistic studies. Our analysis shows distinct injury mechanisms: T\u2010cell\u2010mediated hepatocyte destruction following checkpoint blockade, cytokine\u2010driven bystander injury during cytokine release syndrome, and emerging on\u2010target\/off\u2010tumor toxicity from engineered lymphocytes. Critical risk modifiers include pre\u2010existing liver disease, concomitant hepatotoxic medications, gut microbiome dysbiosis from antibiotic exposure, and host pharmacogenomic variation. We propose three priority research directions: development of predictive biomarkers enabling pretreatment risk stratification, microbiome\u2010directed interventions to preserve hepatic immune tolerance, and implementation of Safety\u2010by\u2010Design engineering strategies that integrate hepatotoxicity prevention into therapeutic design. This review provides a mechanistic framework for transitioning from reactive toxicity management to predictive, personalized prevention, essential for maximizing the therapeutic potential of immune and cell therapies while protecting patient safety in this rapidly expanding treatment landscape.<\/jats:p>","DOI":"10.1002\/med.70093","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:55:50Z","timestamp":1785740150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatotoxicity in the Era of Precision Medicine: Toxicological Mechanisms and Management of Immune and Cell Therapy\u2010Induced Liver Injury"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5846-0395","authenticated-orcid":false,"given":"Yujian","family":"Fan","sequence":"first","affiliation":[{"name":"School of Medicine The Chinese University of Hong Kong Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2907-3841","authenticated-orcid":false,"given":"Xiaokai","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Medicine The Chinese University of Hong Kong Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Lyu","sequence":"additional","affiliation":[{"name":"School of Medicine The Chinese University of Hong Kong Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8011-6085","authenticated-orcid":false,"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine The Chinese University of Hong Kong Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanjie","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Medicine The Chinese University of Hong Kong Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzhen","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Affiliated Hospital of The Chinese University of Hong Kong Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2217-6758","authenticated-orcid":false,"given":"Yisheng","family":"He","sequence":"additional","affiliation":[{"name":"School of Medicine The Chinese University of Hong Kong Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,2]]},"reference":[{"issue":"7","key":"e_1_2_15_2_1","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.6026\/973206300211880","article-title":"Current Trends on Immunotherapy for Oncology","volume":"21","author":"Chander N. 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