| アブストラクト | OBJECTIVE: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database. METHODS: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020. RESULTS: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes. CONCLUSION: Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity. |
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| 投稿者 | Pop, Alexander; Halegoua-DeMarzio, Dina; Barnhart, Huiman; Kleiner, David; Avigan, Mark; Gu, Jiezhun; Chalasani, Naga; Ahmad, Jawad; Fontana, Robert J; Lee, William; Barritt, A Sidney; Durazo, Francisco; Hayashi, Paul H; Navarro, Victor J |
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| 組織名 | Albert Einstein Medical Center, Sidney Kimmel Medical College, Philadelphia, PA,;USA.;Thomas Jefferson University Hospital, Sidney Kimmel Medical College,;Philadelphia, PA, USA.;Duke Clinical Research Institute, Duke University Medical Center, Durham, NC,;National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.;FDA, Silver Spring, MD, USA.;Indiana University School of Medicine, Indianapolis, USA.;Mt. Sinai-Icahn School of Medicine, New York, USA.;University of Michigan, Ann Arbor, MI, USA.;University of Texas, Southwestern, Dallas, TX, USA.;University of North Carolina, Chapel Hill, NC, USA.;University of Southern California Keck School of Medicine, Los Angeles, CA, USA.;USA. victor.navarro@jefferson.edu.;Department of Medicine, Einstein Medical Center; Jefferson Health System,;Philadelphia, PA, 18901, USA. victor.navarro@jefferson.edu. |
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