De Martin Eleonora, Michot Jean-Marie, Rosmorduc Olivier, Guettier Catherine, Samuel Didier
AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, INSERM Unit 1193, Univ Paris-Sud, Université Paris-Saclay, FHU Hépatinov, Villejuif, F-94800, France.
Département d'innovation thérapeutique et d'Essais Précoces (DITEP), Institut Gustave-Roussy, Université Paris Saclay, Villejuif, France.
JHEP Rep. 2020 Aug 11;2(6):100170. doi: 10.1016/j.jhepr.2020.100170. eCollection 2020 Dec.
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（ICI）可改善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；虽然并不常见，但其管理具有挑战性，因为其表现和严重程度极为异质性。健康肝脏或肝硬化肝脏中ICI相关毒性的发生和演变差异尚未阐明。评估因果关系是诊断ICI诱导的肝毒性的关键；肝活检不仅有助于鉴别诊断，还有助于评估肝脏组织学损伤的严重程度。目前的严重程度分类高估了肝损伤的等级，需要进行修订以反映肝病学家的观点。已有报道称ICI相关肝毒性可自发改善，因此糖皮质激素治疗可能应个体化而非系统化。既往有免疫介导性肝炎的患者再次使用ICI是有可能的，但应考虑风险/获益比，因为目前肝炎复发的危险因素尚不清楚。这些患者的管理需要在疗效、毒性和特异性治疗之间取得平衡，因此需要多学科协作。基于大多数癌症中ICI使用的增加，免疫相关肝毒性的发生率将持续上升，这就要求更好地理解和管理这一并发症。
