Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Department of Medicine, Johns Hopkins Medical Institutions, 720 Rutland Ave. Ross 918, Baltimore, MD, 21205, USA.
J Cancer Res Clin Oncol. 2023 Feb;149(2):877-883. doi: 10.1007/s00432-022-04299-1. Epub 2022 Sep 14.
Despite the efficacy of immune checkpoint inhibitors (ICIs), adverse events including hepatotoxicity limit their ongoing use. We investigated the outcomes and management of patients with immune-mediated hepatitis (IMH) and clinical predictors of toxicity resolution.
Patients referred to our multidisciplinary immunotherapy-related toxicity group from August 2017 to December 2020 for IMH were evaluated. Toxicity was defined according to CTCAEv4.0. IMH resolution was defined as liver enzyme normalization after steroid initiation.
Thirty-three patients were included in the study, 62% female, and 71% Caucasian. The most common ICI used was PD-1/PD-L1 (76%). Peak IMH occurred at a median of 89 [45,193] days, for which most patients received 1-2 mg/kg/day prednisone equivalent with 35% requiring MMF. Median follow-up was 123 [33,472] days with IMH resolution seen in 48% of patients at a median of 111 [41,214] days. While high-dose steroid use was not associated with IMH resolution, liver enzyme improvement one week after steroids predicted resolution in univariate analysis (p = 0.041). All 11 patients without IMH resolution died from cancer progression or complications with three patients having acute liver failure. Available liver biopsies showed bile duct injury, with varying degrees of portal and lobular inflammation.
IMH improvement one week after steroid initiation may predict ultimate IMH resolution.
尽管免疫检查点抑制剂 (ICIs) 有效，但包括肝毒性在内的不良反应限制了其持续使用。我们研究了免疫介导性肝炎 (IMH) 患者的结局和管理以及毒性缓解的临床预测因素。
我们评估了 2017 年 8 月至 2020 年 12 月因 IMH 而被转介到我们多学科免疫治疗相关毒性小组的患者。毒性根据 CTCAEv4.0 定义。IMH 缓解定义为起始类固醇后肝酶正常化。
研究纳入了 33 名患者，其中 62%为女性，71%为白种人。最常使用的 ICI 是 PD-1/PD-L1（76%）。IMH 的高峰发生在中位数 89 [45,193] 天，大多数患者接受 1-2mg/kg/ 天泼尼松等效剂量，其中 35%需要使用 MMF。中位随访时间为 123 [33,472] 天，中位数 111 [41,214] 天有 48%的患者出现 IMH 缓解。虽然高剂量类固醇的使用与 IMH 缓解无关，但类固醇治疗一周后肝酶改善与单因素分析中预测缓解相关（p=0.041）。11 名无 IMH 缓解的患者均因癌症进展或并发症死亡，其中 3 例发生急性肝衰竭。可用的肝活检显示胆管损伤，伴有不同程度的门脉和小叶炎症。
类固醇起始后一周的 IMH 改善可能预测最终的 IMH 缓解。
