{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:13:45Z","timestamp":1793060025128,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Reports of moderate to severe liver injury associated with tocilizumab, an interleukin\u20106 (IL\u20106) receptor antagonist, have been reported in the post\u2010marketing setting. This case series aims to characterize cases of tocilizumab\u2010associated clinically significant hepatic injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed cases of severe acute liver injury associated with tocilizumab reported in the FDA Adverse Event Reporting System and the medical literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 12 cases in which tocilizumab was a suspected primary cause of liver injury and eight cases in which serious sequelae of underlying or coincident viral hepatitis were temporally associated with its use. Using the Drug\u2010Induced Liver Injury Network (DILIN) severity scale, five of 12 cases were Grade 5 (two liver transplants, three deaths), one was Grade 4 (liver failure) and six were Grade 3 (serious events with elevated bilirubin). Two cases reported liver atrophy with low hepatocellular expression of Ki\u201067, a marker of cellular proliferation. Among the eight cases of tocilizumab\u2010associated viral hepatitis exacerbation, three were scored as DILIN severity Grade 5 (one liver transplant, two deaths), one was Grade 4 (liver failure), and four were Grade 3. The reported viral hepatitis events were hepatitis B virus (HBV) reactivation (n\u00a0=\u00a03), hepatitis C virus (HCV) flare (n\u00a0=\u00a01), cytomegalovirus (CMV)\u2010induced liver failure (n\u00a0=\u00a01), Epstein\u2010Barr virus hepatitis (n\u00a0=\u00a01), acute hepatitis E (HEV, n\u00a0=\u00a01) and HEV\u2010induced macrophage activation syndrome (n\u00a0=\u00a01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Tocilizumab may be a primary cause of severe liver injury, as well as exacerbate underlying viral hepatitis. The disruption by tocilizumab of IL\u20106\u2010mediated immune protection and hepatocyte regeneration may aggravate clinical outcomes in some cases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14766","type":"journal-article","created":{"date-parts":[[2020,12,20]],"date-time":"2020-12-20T03:25:27Z","timestamp":1608434727000},"page":"515-528","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A case series analysis of serious exacerbations of viral hepatitis and non\u2010viral hepatic injuries in tocilizumab\u2010treated patients"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8719-9638","authenticated-orcid":false,"given":"Ann","family":"Biehl","sequence":"first","affiliation":[{"name":"Office of Pharmacovigilance and Epidemiology US FDA Center for Drug Evaluation and Research Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Harinstein","sequence":"additional","affiliation":[{"name":"Office of Pharmacovigilance and Epidemiology US FDA Center for Drug Evaluation and Research Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Brinker","sequence":"additional","affiliation":[{"name":"Office of Pharmacovigilance and Epidemiology US FDA Center for Drug Evaluation and Research Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Glaser","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Transplant Medicine Office of New Drugs US FDA Center for Drug Evaluation and Research Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Office of Pharmacovigilance and Epidemiology US FDA Center for Drug Evaluation and Research Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Avigan","sequence":"additional","affiliation":[{"name":"Office of Pharmacovigilance and Epidemiology US FDA Center for Drug Evaluation and Research Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Actemra Product Label","author":"Genentech, Inc"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30628-0"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.03.300"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102568"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2020.04.024"},{"key":"e_1_2_11_7_1","volume-title":"Genentech Provides an Update on the Phase III COVACTA Trial of Actemra in Hospitalized Patients With Severe COVID\u201019 Associated Pneumonia","author":"Genentech"},{"key":"e_1_2_11_8_1","volume-title":"Sanofi and Regeneron Provide Update on Kevzara\u00ae (sarilumab) Phase 3 U.S. Trial in COVID\u201019 Patients","author":"Sanofi"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2009.08.003"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.02.004"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201000085"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5291.1379"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4256352"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01057"},{"key":"e_1_2_11_15_1","volume-title":"Actemra Product Label","author":"Genentech, Inc"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40176"},{"key":"e_1_2_11_17_1","unstructured":"Postmarketing reporting of adverse drug experiences. 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