PDF(Pubmed)
Abstract：
BACKGROUND: Immune-related hepatitis (irHepatitis) is a relatively common immune-related adverse event (irAE) of checkpoint inhibitors. Often, it responds well to steroids; however, in refractory cases, further therapy is needed. Anti-tumor necrosis factor (TNF) antibodies are used for management of multiple irAEs, but there are little data in irHepatitis. Here, we report on safety and efficacy of infliximab in 10 cases of steroid-refractory irHepatitis.
METHODS: We retrospectively reviewed patients treated with infliximab for steroid-refractory grade ≥3 irHepatitis at the Department of Dermatology, University Hospital Zurich. The positive response to infliximab was defined as no further increase in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) above 50% than at the time of first infliximab infusion and control of irHepatitis without therapies other than steroids and infliximab.
RESULTS: 10 patients with steroid-resistant irHepatitis grade ≥3 were treated with infliximab 5 mg/kg, of whom 7 (70%) responded positively. In two cases, the liver values increased over 50% before the irHepatitis could be controlled. In another case, therapies other than infliximab and steroids were given. At the median follow-up of 487 days, 90% of the patients demonstrated resolved irHepatitis without AST/ALT elevation following infliximab infusions.
CONCLUSIONS: Treatment of irHepatitis with infliximab did not result in hepatotoxicity and led to long-lasting positive response in 9 of 10 of the cases. Further research is needed to evaluate the role of anti-TNF antibodies in management of irHepatitis.
METHODS: We retrospectively reviewed patients treated with infliximab for steroid-refractory grade ≥3 irHepatitis at the Department of Dermatology, University Hospital Zurich. The positive response to infliximab was defined as no further increase in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) above 50% than at the time of first infliximab infusion and control of irHepatitis without therapies other than steroids and infliximab.
RESULTS: 10 patients with steroid-resistant irHepatitis grade ≥3 were treated with infliximab 5 mg/kg, of whom 7 (70%) responded positively. In two cases, the liver values increased over 50% before the irHepatitis could be controlled. In another case, therapies other than infliximab and steroids were given. At the median follow-up of 487 days, 90% of the patients demonstrated resolved irHepatitis without AST/ALT elevation following infliximab infusions.
CONCLUSIONS: Treatment of irHepatitis with infliximab did not result in hepatotoxicity and led to long-lasting positive response in 9 of 10 of the cases. Further research is needed to evaluate the role of anti-TNF antibodies in management of irHepatitis.
摘要：
背景：免疫相关肝炎（irHepatitis）是检查点抑制剂的一种相对常见的免疫相关不良事件（irAE）。通常,它对类固醇反应良好；然而，在难治性病例中，需要进一步的治疗。抗肿瘤坏死因子（TNF）抗体用于管理多个IRAE，但是关于肝炎的数据很少。这里,我们报道了英夫利昔单抗治疗10例激素难治性肝炎的安全性和有效性.
方法：我们回顾性回顾了在皮肤科接受英夫利昔单抗治疗的患者，苏黎世大学医院。对英夫利昔单抗的阳性反应定义为丙氨酸转氨酶（ALT）/天冬氨酸转氨酶（AST）没有比首次输注英夫利昔单抗时进一步增加50％以上，并且在没有类固醇和英夫利昔单抗以外的治疗的情况下控制了肝炎。
结果：10例类固醇耐药肝炎等级≥3级患者接受英夫利昔单抗5mg/kg治疗，其中7人（70％）积极回应。在两种情况下，在可以控制肝炎之前，肝脏值增加了50％以上。在另一种情况下，给予英夫利昔单抗和类固醇以外的其他治疗.在中位随访487天，90％的患者在英夫利昔单抗输注后表现出无AST/ALT升高的治愈肝炎。
结论：英夫利昔单抗治疗肝炎不会导致肝毒性，并导致10例病例中有9例出现长期阳性反应。需要进一步的研究来评估抗TNF抗体在治疗肝炎中的作用。
方法：我们回顾性回顾了在皮肤科接受英夫利昔单抗治疗的患者，苏黎世大学医院。对英夫利昔单抗的阳性反应定义为丙氨酸转氨酶（ALT）/天冬氨酸转氨酶（AST）没有比首次输注英夫利昔单抗时进一步增加50％以上，并且在没有类固醇和英夫利昔单抗以外的治疗的情况下控制了肝炎。
结果：10例类固醇耐药肝炎等级≥3级患者接受英夫利昔单抗5mg/kg治疗，其中7人（70％）积极回应。在两种情况下，在可以控制肝炎之前，肝脏值增加了50％以上。在另一种情况下，给予英夫利昔单抗和类固醇以外的其他治疗.在中位随访487天，90％的患者在英夫利昔单抗输注后表现出无AST/ALT升高的治愈肝炎。
结论：英夫利昔单抗治疗肝炎不会导致肝毒性，并导致10例病例中有9例出现长期阳性反应。需要进一步的研究来评估抗TNF抗体在治疗肝炎中的作用。
