AP-HP, Département de Dermatologie, Hôpital Saint-Louis, Paris, France; INSERM U976, Paris, France; Université Paris Diderot-Paris VII, Sorbonne Paris Cité, Paris, France.
Université Paris Diderot-Paris VII, Sorbonne Paris Cité, Paris, France; AP-HP, Service de Biostatistiques, Université Paris Diderot-Paris VII, Sorbonne Paris Cité, Hôpital Saint-Louis, Paris, France.
Clin Res Hepatol Gastroenterol. 2021 Mar;45(2):101491. doi: 10.1016/j.clinre.2020.06.016. Epub 2020 Aug 6.
BACKGROUND: Immune-related hepatitis (IRH) occurs in 1 to 18% of immune checkpoint inhibitor (ICI)-treated patients. Steroids are usually recommended for grade≥3 IRH, but their impact on IRH resolution and patient survival remains unclear. METHODS: We retrospectively analyzed a prospective cohort of 339 patients treated at Saint-Louis Hospital (Paris, France) with ICIs for advanced melanoma. Cases of grade≥3 IRH were collected and analyzed. Two groups were compared for their biological features and time for IRH resolution and survival: patients who received steroids (steroids group: SG) and patients who did not (nonsteroids group: NSG). FINDINGS: Grade≥3 IRH was observed in 21 patients. Thirteen were treated with steroids (SG), and 8 were not (NSG). The median time for toxicity resolution was 49 days in SG and 24 days in NSG (P=0.62). All but one patient showed a favorable outcome. Two-year survival was 56% in SG and 54% in NSG (P=0.83). Higher transaminase (P=0.002) and bilirubin (P=0.008) and lower prothrombin (P=0.035) levels were observed in SG than in NSG. For 8 (4 SG/4 NSG) patients, ICI was resumed without any hepatitis relapse. INTERPRETATION: Favorable outcomes may be achieved spontaneously and with no steroids in patients with severe IRH. Steroid initiation should be discussed in cases of high bilirubin levels and decreased prothrombin levels. ICI could be resumed without hepatitis relapse. We propose a management algorithm for grade≥3 IRH that should be validated in larger and prospective cohorts.
背景：免疫相关肝炎（IRH）在 1%至 18%接受免疫检查点抑制剂（ICI）治疗的患者中发生。对于≥3 级 IRH，通常推荐使用类固醇，但它们对 IRH 缓解和患者生存的影响仍不清楚。
方法：我们回顾性分析了圣路易医院（巴黎，法国）收治的 339 例接受 ICI 治疗的晚期黑色素瘤患者的前瞻性队列。收集并分析了≥3 级 IRH 病例。比较了两组患者的生物学特征以及 IRH 缓解和生存时间：接受类固醇治疗的患者（类固醇组：SG）和未接受类固醇治疗的患者（非类固醇组：NSG）。
结果：21 例患者出现≥3 级 IRH。13 例接受类固醇治疗（SG），8 例未接受（NSG）。SG 组毒性缓解的中位时间为 49 天，NSG 组为 24 天（P=0.62）。除 1 例患者外，所有患者均预后良好。SG 和 NSG 的 2 年生存率分别为 56%和 54%（P=0.83）。SG 组的转氨酶（P=0.002）和胆红素（P=0.008）水平较高，而凝血酶原（P=0.035）水平较低。8 例（4 例 SG/4 例 NSG）患者在无肝炎复发的情况下重新开始使用 ICI。
结论：在严重 IRH 患者中，可能无需类固醇即可自发获得良好的结局。对于胆红素水平高和凝血酶原水平降低的患者，应考虑开始使用类固醇。可以在没有肝炎复发的情况下重新开始使用 ICI。我们提出了一种用于≥3 级 IRH 的管理算法，应在更大和前瞻性队列中进行验证。
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