Liver Disease Care Unit, Asahikawa Medical University Hospital, Asahikawa, Japan.
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
J Gastroenterol Hepatol. 2020 Jun;35(6):1042-1048. doi: 10.1111/jgh.14889. Epub 2019 Nov 21.
Because of their survival benefits, immune checkpoint inhibitors (ICIs) are widely administered to patients with various advanced-stage malignancies. During ICI treatment, drug-induced liver injury (DILI) occasionally occurs. In particular, hepatic immune-related adverse events (irAEs) are rare but serious and fatal. In patients with hepatic irAEs, immediate steroid treatment is generally recommended; however, the risk factors for ICI-associated DILI remain unknown. In the present study, we identified a risk factor for ICI-associated DILI.
We retrospectively analyzed 135 patients treated with anti-programmed cell death-1 (PD-1) antibodies, such as nivolumab and pembrolizumab, at Asahikawa Medical University Hospital. We investigated grade ≥ 2 hepatotoxic AEs during anti-PD-1 therapy, and PD-1 inhibitor-associated DILI was then diagnosed according to the Digestive Disease Week Japan (DDW-J) 2004 scale. The risk factors for PD-1 inhibitor-associated DILI were identified by Cox hazard analysis.
Thirty-six patients developed grade ≥ 2 hepatic AEs during anti-PD-1 therapy. Among them, eight patients were diagnosed with PD-1 inhibitor-associated DILI based on the DDW-J 2004 scale. Cox hazard analysis revealed that non-alcoholic fatty liver disease (NAFLD) was a risk factor for PD-1 inhibitor-associated DILI. In addition, we revealed that the outcomes of patients with the DDW-J 2004 score = 3 were improved without steroid treatment.
NAFLD is a potential risk factor for PD-1 inhibitor-associated DILI based on the DDW-J 2004 scale. The DDW-J 2004 scale might be useful for determining whether steroid treatment is required in patients with PD-1 inhibitor-associated DILI.
由于免疫检查点抑制剂（ICIs）具有生存获益，因此广泛用于各种晚期恶性肿瘤患者。在ICI 治疗期间，偶尔会发生药物性肝损伤（DILI）。特别是，肝免疫相关不良事件（irAEs）罕见但严重且致命。在患有肝 irAEs 的患者中，通常建议立即进行类固醇治疗；然而，ICI 相关 DILI 的危险因素仍不清楚。在本研究中，我们确定了 ICI 相关 DILI 的危险因素。
我们回顾性分析了在旭川医科大学医院接受抗程序性细胞死亡-1（PD-1）抗体治疗的 135 例患者，如 nivolumab 和 pembrolizumab。我们研究了抗 PD-1 治疗期间的 2 级及以上肝毒性 AE，并根据日本消化疾病周（DDW-J）2004 标准诊断为 PD-1 抑制剂相关 DILI。通过 Cox 风险分析确定 PD-1 抑制剂相关 DILI 的危险因素。
36 例患者在抗 PD-1 治疗期间出现 2 级及以上肝 AE。其中，8 例患者根据 DDW-J 2004 标准诊断为 PD-1 抑制剂相关 DILI。Cox 风险分析显示，非酒精性脂肪性肝病（NAFLD）是 PD-1 抑制剂相关 DILI 的危险因素。此外，我们发现 DDW-J 2004 评分=3 的患者的结局在没有类固醇治疗的情况下得到改善。
根据 DDW-J 2004 标准，NAFLD 是 PD-1 抑制剂相关 DILI 的潜在危险因素。DDW-J 2004 标准可能有助于确定 PD-1 抑制剂相关 DILI 患者是否需要类固醇治疗。
