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胃癌经检查点抑制剂治疗后发生暴发性肝衰竭:一例报告并文献复习

Fulminant Liver Failure after Treatment with a Checkpoint Inhibitor for Gastric Cancer: A Case Report and Review of the Literature.

作者信息

Dibos Miriam, Dumoulin Johanna, Mogler Carolin, Wunderlich Silke, Reichert Maximilian, Rasch Sebastian, Schmid Roland M, Ringelhan Marc, Ehmer Ursula, Lahmer Tobias

机构信息

Department of Internal Medicine II, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany.

Department of Pathology, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany.

出版信息

J Clin Med. 2023 Jul 12;12(14):4641. doi: 10.3390/jcm12144641.

Abstract

Nivolumab is a promising monoclonal antibody inhibitor of programmed death-1, a protein on the surface of T-cells. As such, it is approved for use in patients with multiple advanced malignancies and can significantly elongate progression-free survival. However, monoclonal antibody inhibitors can lead to adverse hepatic reactions, which in rare cases result in further hepatic damage. Herein, we present a case of a patient with locally advanced gastric carcinoma treated with fluorouracil, oxaliplatin, docetaxel and the checkpoint inhibitor nivolumab. Five months after her first dosage of nivolumab and without a preexisting liver disease, she presented with transaminitis. During the course of her stay, the patient developed status epilepticus, which required mechanical ventilation followed by fulminant hepatic failure. A subsequent liver biopsy revealed severe liver damage with extensive confluent parenchymal necrosis corresponding to checkpoint-inhibitor-induced hepatitis. Alternative reasons for this hepatic failure were ruled out. Despite aggressive therapeutic interventions including corticosteroids and plasma exchange, the patient died due to liver failure. Although hepatic failure is rarely seen in patients with checkpoint inhibitor therapy, it requires early awareness and rapid intervention.

摘要

纳武单抗是一种很有前景的程序性死亡-1单克隆抗体抑制剂,程序性死亡-1是T细胞表面的一种蛋白质。因此,它被批准用于多种晚期恶性肿瘤患者,并且可以显著延长无进展生存期。然而,单克隆抗体抑制剂可导致不良肝脏反应,在罕见情况下会导致进一步的肝损伤。在此,我们报告一例局部晚期胃癌患者,该患者接受了氟尿嘧啶、奥沙利铂、多西他赛和检查点抑制剂纳武单抗治疗。在首次使用纳武单抗五个月后,且无既往肝脏疾病史,她出现了转氨酶升高。在住院期间,患者发生了癫痫持续状态,需要机械通气,随后出现暴发性肝衰竭。随后的肝脏活检显示严重肝损伤,伴有广泛的融合性实质坏死,符合检查点抑制剂诱导的肝炎。排除了导致此次肝衰竭的其他原因。尽管采取了包括皮质类固醇和血浆置换在内的积极治疗干预措施,患者仍因肝衰竭死亡。虽然在接受检查点抑制剂治疗的患者中很少见到肝衰竭,但需要早期识别并迅速干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0d/10381004/6fece1c5962a/jcm-12-04641-g001.jpg

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