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评估肝移植后移植物损伤的核酸生物标志物。

Nucleic acid biomarkers to assess graft injury after liver transplantation.

作者信息

Bardhi Elissa, McDaniels Jennifer, Rousselle Thomas, Maluf Daniel G, Mas Valeria R

机构信息

Surgical Sciences Division, Department of Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.

Program of Transplantation, School of Medicine, University of Maryland, 29 S Greene St, Baltimore, MD 21201, USA.

出版信息

JHEP Rep. 2022 Jan 26;4(3):100439. doi: 10.1016/j.jhepr.2022.100439. eCollection 2022 Mar.

Abstract

Many risk factors and complications impact the success of liver transplantation, such as ischaemia-reperfusion injury, acute rejection, and primary graft dysfunction. Molecular biomarkers have the potential to accurately diagnose, predict, and monitor injury progression or organ failure. There is a critical opportunity for reliable and non-invasive biomarkers to reduce the organ shortage by enabling i) the assessment of donor organ quality, ii) the monitoring of short- and long-term graft function, and iii) the prediction of acute and chronic disease development. To date, no established molecular biomarkers have been used to guide clinical decision-making in transplantation. In this review, we outline the recent advances in cell-free nucleic acid biomarkers for monitoring graft injury in liver transplant recipients. Prior work in this area can be divided into two categories: biomarker discovery and validation studies. Circulating nucleic acids (CNAs) can be found in the extracellular environment pertaining to different biological fluids such as bile, blood, urine, and perfusate. CNAs that are packaged into extracellular vesicles may facilitate intercellular and interorgan communication. Thus, decoding their biological function, cellular origins and molecular composition is imperative for diagnosing causes of graft injury, guiding immunosuppression and improving overall patient survival. Herein, we discuss the most promising molecular biomarkers, their state of development, and the critical aspects of study design in biomarker research for early detection of post-transplant liver injury. Future advances in biomarker studies are expected to personalise post-transplant therapy, leading to improved patient care and outcomes.

摘要

许多风险因素和并发症会影响肝移植的成功率,如缺血再灌注损伤、急性排斥反应和原发性移植肝功能障碍。分子生物标志物有潜力准确诊断、预测和监测损伤进展或器官衰竭。可靠且非侵入性的生物标志物存在一个关键机遇,即通过实现以下几点来减少器官短缺:i)评估供体器官质量;ii)监测短期和长期移植肝功能;iii)预测急性和慢性疾病的发展。迄今为止,尚未有已确立的分子生物标志物用于指导移植中的临床决策。在本综述中,我们概述了用于监测肝移植受者移植损伤的无细胞核酸生物标志物的最新进展。该领域先前的工作可分为两类:生物标志物发现和验证研究。循环核酸(CNA)可在与不同生物流体(如胆汁、血液、尿液和灌注液)相关的细胞外环境中找到。包装在细胞外囊泡中的CNA可能促进细胞间和器官间的通讯。因此,解读它们的生物学功能、细胞起源和分子组成对于诊断移植损伤原因、指导免疫抑制和提高患者总体生存率至关重要。在此,我们讨论最有前景的分子生物标志物、它们的发展状态以及生物标志物研究中用于早期检测移植后肝损伤的研究设计的关键方面。预计生物标志物研究的未来进展将使移植后治疗个性化,从而改善患者护理和预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d8/8856989/4234716a78cd/gr1.jpg

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