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肝细胞癌的免疫治疗:扩大肝移植机会的下一个演进。

Immunotherapy for hepatocellular carcinoma: The next evolution in expanding access to liver transplantation.

机构信息

Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco CA, USA.

Division of HPB Surgery, Hepatology and Liver Transplantation, University of Milan, and Fondazione IRCCS Istituto Nazionale Tumori, Milan Italy.

出版信息

J Hepatol. 2024 Oct;81(4):743-755. doi: 10.1016/j.jhep.2024.05.037. Epub 2024 Jun 5.

Abstract

Immunotherapy has revolutionised the treatment of advanced hepatocellular carcinoma (HCC). In addition, several phase III trials of immunotherapy in combination with surgical or locoregional therapies for early-to intermediate-stage HCC have recently reported positive results, and other phase III trials in the same patient population are currently in progress. As the application of immunotherapy is shifting to include patients with earlier stages of HCC, one looming question now emerges: What is the role of immunotherapy in the pre-liver transplant population? Liver transplantation is a potentially curative therapy for HCC and confers the additional advantage of restoring a normal, healthy liver. In pre-transplant patients, immunotherapy may improve downstaging success and tumour control at the cost of some immunologic risks. These include immune-related toxicities, which are particularly relevant in a uniquely vulnerable population with chronic liver disease, and the possibility of acute rejection after transplantation. Ultimately, the goal of immunotherapy in this population will be to effectively expand access to liver transplantation while preserving pre- and post-transplant outcomes. In this review, we discuss the mechanisms supporting combination immunotherapy, summarise key recent clinical data from major immunotherapy trials, and explore how immunotherapy can be applied in the neoadjuvant setting prior to liver transplantation in selected high-risk patients.

摘要

免疫疗法已经彻底改变了晚期肝细胞癌(HCC)的治疗方法。此外,最近几项关于免疫疗法联合手术或局部区域疗法治疗早期到中期 HCC 的 III 期临床试验报告了积极的结果,其他针对同一患者群体的 III 期临床试验也正在进行中。随着免疫疗法的应用范围扩大到包括 HCC 早期阶段的患者,现在出现了一个悬而未决的问题:免疫疗法在肝移植前人群中的作用是什么?肝移植是 HCC 的一种潜在治愈性疗法,还具有恢复正常健康肝脏的额外优势。在移植前患者中,免疫疗法可能会提高降期成功率和肿瘤控制效果,但要付出一些免疫风险的代价。这些风险包括免疫相关毒性,这在患有慢性肝病的独特脆弱人群中尤为相关,以及移植后发生急性排斥的可能性。最终,该人群中免疫疗法的目标将是在保留移植前和移植后结果的同时,有效地扩大肝移植的机会。在这篇综述中,我们讨论了支持联合免疫疗法的机制,总结了主要免疫疗法试验的最新关键临床数据,并探讨了如何在选定的高危患者的新辅助治疗中在肝移植前应用免疫疗法。

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