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Management and treatment of severe immune-related hepatotoxicity based on clinical and pathological characteristics.
Zhang, Nan; Li, Zhaohui; Liu, Yutao; Shi, Xiaohua; Shi, Di; Li, Yue; Si, Xiaoyan; Xun, Ziyu; Shao, Jing; Zhao, Haitao; Wang, Hanping.
Afiliación
  • Zhang N; Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Beijing, 100730, China.
  • Li Z; Division of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Beijing, 100730, China.
  • Liu Y; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • Shi X; Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Shi D; Department of Emergency Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Li Y; Department of Digestive Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • Si X; Division of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Beijing, 100730, China.
  • Xun Z; Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Beijing, 100730, China.
  • Shao J; Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Beijing, 100730, China.
  • Zhao H; Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Beijing, 100730, China. zhaoht@pumch.cn.
  • Wang H; Division of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Beijing, 100730, China. wanghp@pumch.cn.
Hepatol Int ; 2024 Jul 02.
Article en En | MEDLINE | ID: mdl-38954360
ABSTRACT

BACKGROUND:

The management of severe immune-related hepatotoxicity (irH) needs to be further optimized. This study aims to analyze the clinical characteristics of severe irH; improve the therapeutic strategy, especially salvage treatment in steroid-refractory irH; and determine the safety of immune checkpoint inhibitor (ICPi)-rechallenge.

METHODS:

This multicenter retrospective study included patients who developed severe irH and those without irH after immunotherapy between May 2019 and June 2023. Propensity score matching was used to match these two cohorts with similar baseline characteristics.

RESULTS:

Among 5,326 patients receiving ICPis, 51 patients developed severe irH. irH occurred after a median duration of 36 days and a median of two doses after the first ICPi administration. Patients receiving PD-L1 inhibitors faced a lower risk of developing severe irH. A higher dose of glucocorticoids (GCS) was administered to grade 4 irH than grade 3 irH. For steroid-sensitive patients, grade 4 irH individuals received a higher dosage of GCS than those with grade 3 irH, with no difference in time to resolution. Meanwhile, a significantly higher dose of GCS plus immunosuppression was needed in the steroid-refractory group. Liver biopsy of the steroid-refractory patients exhibited heterogeneous histological features. Twelve patients were retreated with ICPi. No irH reoccurred after a median follow-up of 9.3 months.

CONCLUSION:

irH requires multidimensional evaluation. PD-L1 inhibitors correlated with a lower risk of severe irH. Grade 4 irH demands a higher dose of GCS than recommended. Pathology may guide the salvage treatment for steroid-refractory irH. ICPi rechallenge in severe irH is feasible and safe.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Hepatol Int Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Hepatol Int Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos