SCI

26 September 2024

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

(JHEP Reports, IF: 9.5)

  • Eleonora De Martin, Jean-Marie Michot, Olivier Rosmorduc, Catherine Guettier, Didier Samuel

  • CORRESPONDENCE TO: eleonora.demartin@aphp.fr

Summary 摘要

Immune checkpoint inhibitors (ICIs) improve clinical outcomes in patients suffering from different types of cancer. Liver toxicity is one of the immune-related adverse events associated with immunotherapy; although not common, its management is challenging as it is extremely heterogeneous in terms of presentation and severity. Differences in the development and evolution of ICI-related toxicity in healthy or cirrhotic livers have not yet been elucidated. Assessing causality is key to diagnosing ICI-induced liver toxicity; liver biopsies can assist not only in the differential diagnosis but also in assessing the severity of histological liver damage. The current classification of severity overestimates the grade of liver injury and needs to be revised to reflect the views of hepatologists. Spontaneous improvements in ICI-related liver toxicity have been reported, so corticosteroid therapy should probably be individualised not systematic. The reintroduction of ICIs in a patient with previous immune-mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients, requiring a balance between efficacy, toxicity and specific treatments, necessitates multidisciplinary collaboration. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.

免疫检查点抑制剂(ICIs)改善了不同类型癌症患者的临床结局。肝毒性是与免疫治疗相关的免疫相关不良事件之一;尽管不常见,但由于其在临床表现和严重性方面的极端异质性,管理起来非常具有挑战性。健康肝脏或肝硬化肝脏在ICI相关毒性的发生和演变方面的差异尚未被阐明。评估因果关系是诊断ICI诱发肝毒性的关键;肝活检不仅有助于鉴别诊断,还可以评估肝脏组织损伤的严重程度。目前的严重性分级过高估计了肝损伤的级别,需进行修订以反映肝病学家的观点。有报告指出,ICI相关肝毒性可自发改善,因此糖皮质激素治疗应根据个体情况进行,而不应普遍使用。在曾患有免疫介导性肝炎的患者中重新引入ICIs治疗是可能的,但应考虑风险/收益比,因为目前尚不清楚肝炎复发的风险因素。管理这些患者需要在疗效、毒性和特定治疗之间保持平衡,必须进行多学科合作。随着ICIs在大多数癌症中的广泛应用,免疫相关肝毒性的发生率将继续上升,因此需要对这一并发症进行更深入的理解和管理。


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