| アブストラクト | BACKGROUND AND AIMS: Reports of moderate to severe liver injury associated with tocilizumab, an interleukin-6 (IL-6) receptor antagonist, have been reported in the post-marketing setting. This case series aims to characterize cases of tocilizumab-associated clinically significant hepatic injury. METHODS: We analysed cases of severe acute liver injury associated with tocilizumab reported in the FDA Adverse Event Reporting System and the medical literature. RESULTS: 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-Induced 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-67, a marker of cellular proliferation. Among the eight cases of tocilizumab-associated 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 = 3), hepatitis C virus (HCV) flare (n = 1), cytomegalovirus (CMV)-induced liver failure (n = 1), Epstein-Barr virus hepatitis (n = 1), acute hepatitis E (HEV, n = 1) and HEV-induced macrophage activation syndrome (n = 1). CONCLUSION: Tocilizumab may be a primary cause of severe liver injury, as well as exacerbate underlying viral hepatitis. The disruption by tocilizumab of IL-6-mediated immune protection and hepatocyte regeneration may aggravate clinical outcomes in some cases. |
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| ジャーナル名 | Liver international : official journal of the International Association for the Study of the Liver |
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| 投稿日 | 2020/12/16 |
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| 投稿者 | Biehl, Ann; Harinstein, Lisa; Brinker, Allen; Glaser, Rachel; Munoz, Monica; Avigan, Mark |
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| 組織名 | Office of Pharmacovigilance and Epidemiology, US FDA Center for Drug Evaluation;and Research, Silver Spring, MD, USA.;Division of Rheumatology and Transplant Medicine, Office of New Drugs, US FDA;Center for Drug Evaluation and Research, Silver Spring, MD, USA. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/33320444/ |
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