Institute of Immunobiology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007, St. Gallen, Switzerland.
Department of Dermatology, Venereology and Allergology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007, St. Gallen, Switzerland.
J Cancer Res Clin Oncol. 2022 Mar;148(3):647-656. doi: 10.1007/s00432-021-03870-6. Epub 2021 Dec 7.
Immune checkpoint inhibitor (ICI)-induced hepatitis belongs to the frequently occurring immune-related adverse events (irAEs), particularly with the combination therapy involving ipilimumab and nivolumab. However, predisposing factors predicting the occurrence of ICI-induced hepatitis are barely known. We investigated the association of preexisting autoantibodies in the development of ICI-induced hepatitis in a prospective cohort of cancer patients.
Data from a prospective biomarker cohort comprising melanoma and non-small cell lung cancer (NSCLC) patients were used to analyze the incidence of ICI-induced hepatitis, putatively associated factors, and outcome.
40 patients with melanoma and 91 patients with NSCLC received ICI between July 2016 and May 2019. 11 patients developed ICI-induced hepatitis (8.4%). Prior to treatment, 45.5% of patients in the hepatitis cohort and 43.8% of the control cohort showed elevated titers of autoantibodies commonly associated with autoimmune liver diseases (p = 0.82). We found two nominally significant associations between the occurrence of ICI-induced hepatitis and HLA alleles associated with autoimmune liver diseases among NSCLC patients. Of note, significantly more patients with ICI-induced hepatitis developed additional irAEs in other organs (p = 0.0001). Neither overall nor progression-free survival was affected in the hepatitis group.
We found nominally significant associations of ICI-induced hepatitis with two HLA alleles. ICI-induced hepatitis showed no correlation with liver-specific autoantibodies, but frequently co-occurred with irAEs affecting other organs. Unlike other irAEs, ICI-induced hepatitis is not associated with a better prognosis.
免疫检查点抑制剂（ICI）诱导的肝炎属于常见的免疫相关不良反应（irAE），特别是涉及伊匹单抗和纳武利尤单抗的联合治疗。然而，预测 ICI 诱导的肝炎发生的易患因素知之甚少。我们在癌症患者的前瞻性队列中研究了预先存在的自身抗体与 ICI 诱导的肝炎发生的相关性。
使用包含黑色素瘤和非小细胞肺癌（NSCLC）患者的前瞻性生物标志物队列的数据来分析 ICI 诱导的肝炎的发生率、潜在相关因素和结果。
40 名黑色素瘤患者和 91 名 NSCLC 患者在 2016 年 7 月至 2019 年 5 月期间接受了 ICI 治疗。11 名患者发生了 ICI 诱导的肝炎（8.4%）。在治疗前，肝炎组 45.5%的患者和对照组 43.8%的患者自身抗体滴度升高，这些自身抗体通常与自身免疫性肝病相关（p=0.82）。我们发现，在 NSCLC 患者中，与自身免疫性肝病相关的 HLA 等位基因与 ICI 诱导的肝炎发生之间存在两个名义上的显著相关性。值得注意的是，发生 ICI 诱导的肝炎的患者发生其他器官的附加 irAE 的比例显著更高（p=0.0001）。无论是总体生存率还是无进展生存率，在肝炎组中均未受到影响。
我们发现 ICI 诱导的肝炎与两个 HLA 等位基因存在名义上的相关性。ICI 诱导的肝炎与肝脏特异性自身抗体无关，但常与影响其他器官的 irAE 同时发生。与其他 irAE 不同，ICI 诱导的肝炎与更好的预后无关。
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