mTOR 抑制剂在小儿肝移植受者中的作用:系统综述

IF 3.4 3区 医学 Q1 PEDIATRICS
Marjan Moghadamnia, Simin Dashti-Khavidaki, Hosein Alimadadi
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引用次数: 0

摘要

背景免疫抑制药物在决定肝移植(LT)后器官和患者存活率方面起着至关重要的作用。通常,小儿肝移植患者的免疫抑制方案依赖于钙神经蛋白抑制剂(CNIs)。虽然哺乳动物雷帕霉素靶点抑制剂(mTOR)已在成人肝移植受者中显示出有益的结果,如改善肝移植后的肾功能,但由于疗效不确定和潜在的不良反应,它们在小儿肝移植受者中的应用仍是一个争论的话题。方法本系统综述遵循系统综述和荟萃分析首选报告项目(PRISMA)协议进行和报告。使用特定术语和关键词检索了截至 2023 年 8 月 31 日的数据库。结果在确定的888篇文章中,有30项研究符合纳入标准,涉及386名接受肝移植并接受基于mTOR抑制剂的免疫抑制方案的儿童。对于肾功能受损的LT儿科患者,从CNI转为mTOR抑制剂或在CNI降低免疫抑制的基础上添加mTOR抑制剂的有益影响尚存在争议,需要进行高强度的临床研究。通过在 CNI 中添加 mTOR 抑制剂来增强免疫抑制似乎有助于正在经历难治性急性排斥反应或慢性排斥反应的小儿 LT 受者。含 mTOR 抑制剂的治疗方案未能减少 LT 儿童移植后淋巴组织增生性疾病(PTLD)的发生,这可能是由于所研究的患者中同时存在高浓度的 CNI。mTOR抑制剂治疗PTLD的疗效仍不确定;不过,对于排斥反应风险较高的PTLD患者,可以使用mTOR抑制剂。对于因肝恶性肿瘤(如肝母细胞瘤或肝细胞癌)而接受移植的儿科患者,或移植后患有原发性或复发性恶性肿瘤的患者,改用或在维持性免疫抑制剂中添加 mTOR 抑制剂似乎比较合适。改用 mTOR 抑制剂可改善某些 CNI 相关不良反应,如牙龈增生、神经毒性、肾病、肥厚性心肌病或血栓性微血管病。结论虽然mTOR抑制剂在接受肝移植的儿科患者中的确切作用还需要进一步研究,但本综述提出了两种算法,以指导可能受益于该类药物的儿科患者从CNIs转为mTOR抑制剂,或在CNI最小化免疫抑制方案中添加mTOR抑制剂。本综述主要由样本量不足的回顾性研究组成,缺乏对照组,这是本研究的主要局限性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Role of mTOR Inhibitors in Pediatric Liver Transplant Recipients: A Systematic Review

Role of mTOR Inhibitors in Pediatric Liver Transplant Recipients: A Systematic Review

Background

Immunosuppressive medications play a crucial role in determining both organ and patient survival following liver transplantation (LT). Typically, immunosuppressive protocols for pediatric LT patients rely on calcineurin inhibitors (CNIs). While inhibitors of mammalian target of rapamycin (mTOR) have demonstrated beneficial outcomes in adult recipients of liver allografts, such as improved renal function post-LT, their application in pediatric liver transplant recipients is a subject of debate due to uncertain efficacy and potential adverse effects.

Objectives

This review evaluates the potential roles of mTOR inhibitors in the context of pediatric LT patients.

Methods

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol for conduct and reporting. Databases until 31 August 2023 were searched using specific terms and keywords. All clinical studies focusing on mTOR inhibitors in pediatric LT were included.

Results

Out of 888 identified articles, 30 studies, involving 386 children who had undergone liver transplantation and received mTOR-inhibitor-based immunosuppressive regimens, met the inclusion criteria. The beneficial impacts of switching from a CNI to an mTOR inhibitor or adding an mTOR inhibitor to CNI-reduced immunosuppression in LT pediatric patients with impaired kidney function are controversial, and high-powered clinical studies are need. It appears that enhancing immunosuppression by adding an mTOR inhibitor to CNI is helpful for pediatric LT recipients who are experiencing refractory acute rejection or chronic rejection. mTOR-inhibitor-containing regimens failed to reduce the occurrence of post-transplant lymphoproliferative disorders (PTLD) among children with LT that may be due to concomitant high CNI concentration among studied patients. The effectiveness of mTOR inhibitors in treating PTLD remains uncertain; however, in patients with PTLD who are at high risk of rejection, mTOR inhibitors may be administered. Conversion to or the addition of mTOR inhibitors to maintenance immunosuppression seems to be suitable for pediatric patients who received a transplant due to hepatic malignancies such as hepatoblastoma or hepatocellular carcinoma or for those with post-transplant primary or recurrent malignancies. Switching to an mTOR inhibitor may improve some CNI-related adverse effects such as gingival hyperplasia, neurotoxicity, nephropathy, hypertrophic cardiomyopathy, or thrombotic microangiopathy.

Conclusion

Although the exact role of mTOR inhibitors among pediatric patients who have received a liver transplant needs further study, two algorithms are presented in this review to guide conversion from CNIs to mTOR inhibitors or the addition of mTOR inhibitor to a CNI-minimization immunosuppressive regimen for pediatric patients who may benefit from this class of drugs. This review mainly consisted of retrospective studies with inadequate sample sizes and lacked a control group, which represents the main limitation of this study.

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来源期刊
Pediatric Drugs
Pediatric Drugs PEDIATRICS-PHARMACOLOGY & PHARMACY
CiteScore
7.20
自引率
0.00%
发文量
54
审稿时长
>12 weeks
期刊介绍: Pediatric Drugs promotes the optimization and advancement of all aspects of pharmacotherapy for healthcare professionals interested in pediatric drug therapy (including vaccines). The program of review and original research articles provides healthcare decision makers with clinically applicable knowledge on issues relevant to drug therapy in all areas of neonatology and the care of children and adolescents. The Journal includes: -overviews of contentious or emerging issues. -comprehensive narrative reviews of topics relating to the effective and safe management of drug therapy through all stages of pediatric development. -practical reviews covering optimum drug management of specific clinical situations. -systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. -Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in the pediatric population. -original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Pediatric Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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