Treatment of Refractory Checkpoint-Inhibitor-Induced Hepatitis with Tacrolimus: A Case and Review of the Literature

R. De Wilde, Michael Saerens, A. Hoorens, A. Geerts, C. Jacobs
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Abstract

Immune-related hepatitis (irH) is a fairly frequent complication of immune checkpoint inhibitors (ICIs). Its management is generally based on withholding ICIs and on the rapid initiation of corticosteroids, which is successful in 63 to 96% of cases. Mycofenolate mofetil (MMF) is accepted as a second-line immunosuppressant in the case of the failure of corticosteroids. In rare cases, though, irH is also resistant to MMF and may lead to liver failure. There are no standard third-line treatments and current guidelines are based on a limited number of case reports. We present a case of a metastatic melanoma patient with an immune-related hepatitis refractory to corticosteroids and MMF, that was successfully reversed with tacrolimus. Unfortunately, this was complicated with a serious infection and progressive disease, which illustrates the complexity of treatment of steroid-refractory immunotherapy-related adverse events. Furthermore, we provided a literature review regarding the management of steroid-refractory hepatitis and proposed a strategy to circumvent the current uncertainties in the management of steroid-refractory irH.
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他克莫司治疗难治性检查点抑制剂性肝炎1例及文献复习
免疫相关性肝炎(irH)是免疫检查点抑制剂(ICIs)相当常见的并发症。其管理一般是基于停止注射胰岛素和迅速开始使用皮质类固醇,这在63%至96%的病例中是成功的。霉酚酸酯(MMF)被认为是在皮质类固醇失败的情况下的二线免疫抑制剂。然而,在极少数情况下,irH也对MMF具有耐药性,并可能导致肝衰竭。没有标准的三线治疗方法,目前的指导方针是基于数量有限的病例报告。我们报告一例转移性黑色素瘤患者伴免疫相关性肝炎,对皮质类固醇和MMF难治性,他克莫司成功逆转。不幸的是,这伴有严重感染和疾病进展,这说明了治疗类固醇难治性免疫治疗相关不良事件的复杂性。此外,我们提供了一篇关于类固醇难治性肝炎管理的文献综述,并提出了一种策略来规避目前类固醇难治性irH管理的不确定性。
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来源期刊
Journal of International Translational Medicine
Journal of International Translational Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
自引率
0.00%
发文量
317
审稿时长
8 weeks
期刊介绍: Journal of International Translational Medicine (JITM, ISSN 2227-6394), founded in 2012, is an English academic journal published by Journal of International Translational Medicine Co., Ltd and sponsored by International Fderation of Translational Medicine. JITM is an open access journal freely serving to submit, review, publish, read and download full text and quote. JITM is a quarterly publication with the first issue published in March, 2013, and all articles published in English are compiled and edited by professional graphic designers according to the international compiling and editing standard. All members of the JITM Editorial Board are the famous international specialists in the field of translational medicine who come from twenty different countries and areas such as USA, Britain, France, Germany and so on.
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