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Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: a compromise between the risk of recurrence and the risk of rejection?

机译:在肝细胞癌肝移植受者中使用断奶的免疫抑制方案:复发风险与排斥风险之间的折衷方案?

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摘要

Hepatocellular carcinoma (HCC) recurrence rate after liver transplantation (LT) is still up to 15–20%, despite a careful selection of candidates and optimization of the management within the waiting list. To reduce tumour recurrence, the currently adopted post-transplant strategies are based on the administration of a tailored immunosuppression (IS) regimen. Drug-induced depression of the immune system is essential in preventing graft rejection, however has a well-established association with oncogenesis. The immune system has a key role as a defending mechanism against cancer development, preventing vascular invasion and metastasis. Thus, IS drugs represent one of few modifiable non-oncological risk factors for tumour recurrence. In HCC recipients, a tailored IS therapy, with the aim to minimize drugs’ doses, is essential to gain the optimal balance between the risk of rejection and the risk of tumour recurrence. So far, a complete withdrawal of IS drugs after LT is reported to be safely achievable in 25% of patients (defined as “operational tolerant”), without the risk of patient and graft loss. The recent identification of non-invasive “bio-markers of tolerance”, which permit to identify patients who could successfully withdraw IS therapies, opens new perspectives in the management of HCC after LT. IS withdrawal could potentially reduce the risk of tumour recurrence, which represents the major drawback in HCC recipients. Herein, we review the current literature on IS weaning in patients who underwent LT for HCC as primary indication and we report the largest experiences on IS withdrawal in HCC recipients.
机译:尽管精心挑选了候选人并在候补名单中进行了优化,但肝移植(LT)后的肝细胞癌(HCC)复发率仍高达15–20%。为了减少肿瘤复发,当前采用的移植后策略是基于量身定制的免疫抑制(IS)方案。药物引起的免疫系统抑制对于防止移植物排斥是必不可少的,但是与肿瘤的发生有着良好的联系。免疫系统作为抵抗癌症发展,预防血管入侵和转移的防御机制具有关键作用。因此,IS药物是肿瘤复发的少数可修改的非肿瘤危险因素之一。在HCC接受者中,量身定制的IS治疗旨在最大程度地减少药物剂量,对于在排斥风险和肿瘤复发风险之间取得最佳平衡至关重要。到目前为止,据报道25%的患者可以安全地完全撤消LT后IS药物(定义为“手术耐受性”),而无患者和移植物丢失的风险。最近对非侵入性“耐受性生物标志物”的鉴定使人们能够鉴定出可以成功退出IS治疗的患者,为LT后HCC的治疗开辟了新的前景。停用IS可能会降低肿瘤复发的风险,这代表了HCC接受者的主要缺点。本文中,我们回顾了接受LT肝癌作为主要适应症患者的IS断奶的最新文献,并且我们报告了HCC接受者在IS戒断方面的最大经验。

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