Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine, Izumo, Japan.
Department of Gastroenterology and Hepatology, Shimane University Faculty of Medicine, Izumo, Japan.
Thorac Cancer. 2023 May;14(13):1208-1211. doi: 10.1111/1759-7714.14859. Epub 2023 Mar 19.
An 82-year-old man was treated with ipilimumab and nivolumab for malignant pleural mesothelioma. Although he was previously treated with prednisolone (1 mg/kg/day) for immune-related adverse event (irAE) hepatitis by a previous doctor, he still had worsening liver function and was transferred to our hospital. Blood tests and imaging findings were negative for autoimmune and infectious hepatitis, and liver biopsy results were consistent with irAE hepatitis. Steroid pulse therapy improved liver function, but tapering to prednisolone (1 mg/kg/day) again worsened his liver function. Concomitant use of mycophenolate mofetil was initiated, but no improvement in liver function was observed, therefore azathioprine, a thiopurine immunosuppressant, was administered in combination with steroids. During the course of treatment, hepatic dysfunction due to azathioprine was suspected, and the concomitant use of mercaptopurine and prednisolone was started. Afterward, the liver function improved, and the prednisolone dose was gradually reduced to 10 mg/day. This is a rare case in which a thiopurine-based immunosuppressant was effective against irAE hepatitis, therefore thiopurine-based immunosuppressants may be effective against steroid-refractory hepatitis.
一位 82 岁男性因恶性胸膜间皮瘤接受了伊匹单抗和纳武利尤单抗治疗。尽管他之前曾因免疫相关不良反应（irAE）性肝炎接受过一位医生的泼尼松龙（1mg/kg/天）治疗，但他的肝功能仍在恶化，并被转至我院。血液检查和影像学检查结果均排除了自身免疫性和传染性肝炎，肝活检结果与 irAE 性肝炎一致。类固醇脉冲疗法改善了肝功能，但再次将泼尼松龙（1mg/kg/天）减量时肝功能再次恶化。因此开始合用吗替麦考酚酯，但肝功能未见改善，因此加用了硫唑嘌呤（一种免疫抑制剂）与类固醇联合治疗。在治疗过程中，怀疑因硫唑嘌呤引起了肝功能障碍，开始合用巯嘌呤和泼尼松龙。之后，肝功能改善，泼尼松龙剂量逐渐减至 10mg/天。这是一个罕见的案例，硫唑嘌呤类免疫抑制剂对 irAE 性肝炎有效，因此硫唑嘌呤类免疫抑制剂可能对类固醇难治性肝炎有效。
