Department of Internal Medicine, University of Maryland Midtown Campus, Baltimore, Maryland, USA.
Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Hepatol Commun. 2024 Sep 18;8(10). doi: 10.1097/HC9.0000000000000525. eCollection 2024 Oct 1.
In recent years, the use of immune checkpoint inhibitors (ICIs) has become a cornerstone in cancer treatment. However, this has also resulted in the emergence of immune-related adverse events, notably ICI hepatitis, posing a significant clinical challenge. While steroids are the primary treatment, there are increasing cases of steroid-refractory ICI hepatitis. Our objective is to investigate the management of ICI hepatitis and its response to steroid treatment.
PubMed/MEDLINE, EMBASE, and CENTRAL databases were searched in July 2023 based on keywords including ICIs (anti-Programmed cell death protein 1/Programmed Death-Ligand 1, anti-CTLA-4, and anti-LAG3) and hepatitis.
A total of 4358 studies were screened, and 44 studies were included in this systematic review. One thousand eight hundred fifty-six patients with ICI hepatitis were included (grade 1-2: 31.7%, grade 3-4: 56.0%, and unknown: 12.3%) with 1184 patients who received corticosteroid treatment. The duration of treatment and dosage varied considerably across the studies. Mycophenolate mofetil was the predominant agent used in 68 out of 82 cases (82.9%), followed by infliximab and azathioprine. A summary estimate of the proportion of steroid-refractory hepatitis in a random effects model was 16% (95% CI: 11%-23%). An estimated 40% (95% CI: 30%-51%) of patients of all patients with ICI hepatitis were rechallenged with an ICI, and of those rechallenged, there was an estimated 22% (95% CI: 15%-30%) recurrence.
Corticosteroids are the primary treatment for ICI hepatitis, with mycophenolate mofetil used as a secondary option for steroids-refractory cases. Current practices mostly rely on expert consensus, highlighting the need for further research to validate and optimize these treatments, particularly for steroid-resistant cases.
近年来，免疫检查点抑制剂（ICIs）的应用已成为癌症治疗的基石。然而，这也导致了免疫相关不良反应的出现，特别是ICI 肝炎，这给临床带来了重大挑战。虽然类固醇是主要治疗药物，但类固醇难治性 ICI 肝炎的病例越来越多。我们的目的是研究 ICI 肝炎的治疗管理及其对类固醇治疗的反应。
根据关键词（包括 ICIs（抗程序性细胞死亡蛋白 1/程序性死亡配体 1、抗 CTLA-4 和抗 LAG3）和肝炎），于 2023 年 7 月在 PubMed/MEDLINE、EMBASE 和 CENTRAL 数据库中进行了检索。
共筛选出 4358 项研究，其中纳入了 44 项系统性综述研究。共纳入了 1856 例 ICI 肝炎患者（1 级-2 级：31.7%，3 级-4 级：56.0%，未知：12.3%），其中 1184 例接受了皮质类固醇治疗。治疗的持续时间和剂量在不同研究之间差异很大。在 82 例中，霉酚酸酯是主要药物（68 例，82.9%），其次是英夫利昔单抗和硫唑嘌呤。在随机效应模型中，类固醇难治性肝炎的比例估计为 16%（95%CI：11%-23%）。在所有 ICI 肝炎患者中，估计有 40%（95%CI：30%-51%）的患者重新接受了 ICI 治疗，而在这些重新接受治疗的患者中，估计有 22%（95%CI：15%-30%）的患者出现复发。
类固醇是 ICI 肝炎的主要治疗药物，对于类固醇难治性病例，霉酚酸酯可作为二线药物。目前的治疗方法主要依赖专家共识，这突显了需要进一步研究来验证和优化这些治疗方法，特别是对于类固醇耐药性病例。
