Onishi Sachiyo, Tajika Masahiro, Bando Hideaki, Matsubara Yuki, Hosoda Waki, Muro Kei, Niwa Yasumasa
Department of Endoscopy, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
J Med Case Rep. 2020 Nov 26;14(1):230. doi: 10.1186/s13256-020-02541-3.
Immune checkpoint inhibitors have shown clinically significant antitumor efficacy and have been approved for the treatment of various kinds of advanced malignancies. On the other hand, these immunotherapies show unique adverse events, termed "immune-related adverse events," which are distinctly associated with conventional cytotoxic chemotherapy. Hepatotoxicity is recognized as an immune-related adverse event; prompt treatment with corticosteroids is recommended. However, some cases are refractory to steroids. Here, we report the first case (to our knowledge) of steroid-refractory immune-related hepatitis that was successfully treated with ursodeoxycholic acid and bezafibrate.
A 68-year-old Asian man, came to our hospital for the treatment of malignant melanoma involving the gingiva and presenting with multiple lymph node and bone metastases was administered nivolumab as a first-line treatment. Two months into treatment, the patient developed diarrhea as a result of immune-related colitis; the colitis was treated successfully with prednisolone 60 mg/ day, resulting in improvement in the patient's symptoms. However, when steroids were being tapered, acute elevation of liver enzymes was observed. Autoimmune hepatitis was suspected as an immune-related adverse event, and treatment with intravenous prednisolone 60 mg/ day was reinitiated. However, restoration of the steroid treatment failed to improve the patient's liver enzymes. On the basis of histological findings from liver biopsy and exclusion of other etiologies such as viral infection and other drug-induced hepatitis, steroid-refractory hepatic immune-related adverse event was deemed the most likely cause of the patient's acute hepatitis. In general, mycophenolate mofetil or tacrolimus is known to provide benefits in cases of steroid-refractory hepatitis. We therefore decided to add oral ursodeoxycholic acid and bezafibrate in consideration of the patient's background of repeated aspiration pneumonia. Administration of this regimen resulted in an improvement in liver function, which remained normal even after tapering of prednisolone.
Ursodeoxycholic acid and bezafibrate may be useful for treatment of steroid-refractory immune-related adverse event hepatitis.
免疫检查点抑制剂已显示出具有临床意义的抗肿瘤疗效，并已被批准用于治疗各种晚期恶性肿瘤。另一方面，这些免疫疗法会出现独特的不良事件，称为“免疫相关不良事件”，这与传统的细胞毒性化疗明显不同。肝毒性被认为是一种免疫相关不良事件；建议使用皮质类固醇进行及时治疗。然而，有些病例对类固醇治疗无效。在此，我们报告了首例（据我们所知）用熊去氧胆酸和苯扎贝特成功治疗的类固醇难治性免疫相关肝炎病例。
一名68岁的亚洲男性因牙龈恶性黑色素瘤伴多发淋巴结和骨转移到我院就诊，接受纳武单抗作为一线治疗。治疗两个月后，患者因免疫相关结肠炎出现腹泻；用泼尼松龙60mg/天成功治疗了结肠炎，患者症状得到改善。然而，当逐渐减少类固醇用量时，观察到肝酶急性升高。怀疑自身免疫性肝炎是一种免疫相关不良事件，重新开始静脉注射泼尼松龙60mg/天进行治疗。然而，恢复类固醇治疗未能改善患者的肝酶水平。根据肝活检的组织学结果并排除其他病因，如病毒感染和其他药物性肝炎，类固醇难治性肝脏免疫相关不良事件被认为是患者急性肝炎最可能的原因。一般来说，已知霉酚酸酯或他克莫司对类固醇难治性肝炎病例有益。因此，考虑到患者有反复吸入性肺炎的病史，我们决定加用口服熊去氧胆酸和苯扎贝特。使用该方案后肝功能得到改善，即使在逐渐减少泼尼松龙用量后仍保持正常。
熊去氧胆酸和苯扎贝特可能对治疗类固醇难治性免疫相关不良事件性肝炎有用。
