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免疫检查点抑制剂诱导的免疫介导性肝炎:当前进展与未来展望

Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives.

作者信息

Liu Zherui, Zhu Yun, Xie Huan, Zou Zhengsheng

机构信息

Medical School of Chinese PLA, Beijing, China.

Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China.

出版信息

Front Pharmacol. 2023 Jan 9;13:1077468. doi: 10.3389/fphar.2022.1077468. eCollection 2022.


DOI:10.3389/fphar.2022.1077468
PMID:36699050
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9868416/
Abstract

In recent years, cancer immunotherapy has made remarkable achievements. Immune checkpoint inhibitors (ICIs) have been used successfully in several types of cancer in the past decade. However, expanded indication and increased use of Immune checkpoint inhibitors have resulted in increased reports of toxicity called immune-related adverse events (irAEs). Due to the unique immunological characteristics of the liver, a hepatic immune-related adverse events has also been reported, which is usually termed Immune-mediated hepatitis (IMH). So far, it is generally considered that the mechanism of IMH induced by Immune checkpoint inhibitors is mainly the overactivation of T cells. It has been reported that the incidence of IMH ranges from 1% to 15%. Because of the lack of specific markers, a diagnosis of exclusion of IMH is critical. Although most IMH is mild and recoverable, several death cases have been reported, which has been increasingly concerned. This review summarizes the current understanding of the pathophysiology, epidemiology, diagnosis, management and prognosis of IMH caused by Immune checkpoint inhibitors. It also discusses the controversial issues in IMH, such as the role of liver biopsy, grading criteria, risk factors, rational treatment strategies with steroids, and the timing of Immune checkpoint inhibitors rechallenging, which may provide helpful information for IMH in future clinical practice.

摘要

近年来,癌症免疫疗法取得了显著成就。在过去十年中,免疫检查点抑制剂(ICIs)已成功应用于多种类型的癌症。然而,免疫检查点抑制剂适应证的扩大和使用的增加导致了称为免疫相关不良事件(irAEs)的毒性报告增多。由于肝脏独特的免疫学特性,也有肝免疫相关不良事件的报道,通常称为免疫介导性肝炎(IMH)。迄今为止,普遍认为免疫检查点抑制剂诱导IMH的机制主要是T细胞过度活化。据报道,IMH的发生率为1%至15%。由于缺乏特异性标志物,排除性诊断IMH至关重要。尽管大多数IMH症状轻微且可恢复,但已有数例死亡病例报道,这一情况日益受到关注。本综述总结了目前对免疫检查点抑制剂所致IMH的病理生理学、流行病学、诊断、管理及预后的认识。还讨论了IMH中存在争议的问题,如肝活检的作用、分级标准、危险因素、类固醇的合理治疗策略以及免疫检查点抑制剂再次使用的时机等,这可能为未来临床实践中IMH的诊治提供有益信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b237/9868416/018c2ef1dcda/fphar-13-1077468-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b237/9868416/a3a1dfeefe56/fphar-13-1077468-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b237/9868416/018c2ef1dcda/fphar-13-1077468-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b237/9868416/a3a1dfeefe56/fphar-13-1077468-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b237/9868416/018c2ef1dcda/fphar-13-1077468-g002.jpg

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Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives.

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[6]
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[8]
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引用本文的文献

[1]
A retrospective study of clinical characteristics and steroid therapy in immune checkpoint inhibitor-mediated hepatitis.

Ther Adv Med Oncol. 2025-8-10

[2]
Neoadjuvant immunotherapy for resectable primary liver cancer (Review).

Oncol Lett. 2025-7-23

[3]
Bimodal onset and pan-cancer uniformity of immune-mediated liver injury: a retrospective cohort study.

Front Immunol. 2025-7-2

[4]
Drug-Induced Autoimmune Hepatitis: Robust Causality Assessment Using Two Different Validated and Scoring Diagnostic Algorithms.

Diagnostics (Basel). 2025-6-23

[5]
Oncohepatology: Navigating liver injury in the era of modern cancer therapy.

World J Hepatol. 2025-6-27

[6]
Case Report: Regenerative hepatic pseudotumor induced by tislelizumab in a lung cancer patient.

Front Immunol. 2025-5-30

[7]
Uncovering prognostic biomarkers through a pharmacovigilance study: the case of RDW.

Clin Transl Oncol. 2025-6-15

[8]
Editorial: Harnessing single-cell insights: pioneering predictive markers for immunotherapy efficacy in solid tumors.

Front Immunol. 2025-5-19

[9]
Combining immune checkpoints with TNFSF agonists: a new horizon for cancer and autoimmune therapies.

Front Immunol. 2025-3-17

[10]
Germline prediction of immune checkpoint inhibitor discontinuation for immune-related adverse events.

J Immunother Cancer. 2025-3-28

本文引用的文献

[1]
The use of tacrolimus in the management of checkpoint inhibitor immunotherapy-induced hepatitis.

J R Coll Physicians Edinb. 2022-3

[2]
Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study.

Lancet Oncol. 2022-6

[3]
Retreatment With Immune Checkpoint Inhibitors After a Severe Immune-Related Hepatitis: Results From a Prospective Multicenter Study.

Clin Gastroenterol Hepatol. 2023-3

[4]
The Role of Myeloid Cells in Hepatotoxicity Related to Cancer Immunotherapy.

Cancers (Basel). 2022-4-10

[5]
Survival with Cemiplimab in Recurrent Cervical Cancer.

N Engl J Med. 2022-2-10

[6]
Corticosteroids for high-grade immune checkpoint inhibitor-mediated hepatitis: Is less more?

Hepatology. 2022-3

[7]
Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma.

N Engl J Med. 2022-1-6

[8]
Hepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors.

Cancers (Basel). 2021-11-12

[9]
Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma.

J Clin Oncol. 2022-1-10

[10]
Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.

J Clin Oncol. 2021-12-20

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