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采用体外血液净化技术的肝脏替代疗法:当前认知与未来方向

Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions.

作者信息

Papamichalis Panagiotis, Oikonomou Katerina G, Valsamaki Asimina, Xanthoudaki Maria, Katsiafylloudis Periklis, Papapostolou Evangelia, Skoura Apostolia-Lemonia, Papamichalis Michail, Karvouniaris Marios, Koutras Antonios, Vaitsi Eleni, Sarchosi Smaragdi, Papadogoulas Antonios, Papadopoulos Dimitrios

机构信息

Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Thessaly, Greece.

Department of Transfusion Medicine, University Hospital of Larissa, Larissa 41110, Thessaly, Greece.

出版信息

World J Clin Cases. 2023 Jun 16;11(17):3932-3948. doi: 10.12998/wjcc.v11.i17.3932.

Abstract

Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to restore impaired liver function with artificial extracorporeal blood purification systems. The first such systems were developed at the end of the 20 century, providing solutions as bridging therapy, either for liver recovery or LT. They enhance the elimination of metabolites and substances that accumulate due to compromised liver function. In addition, they aid in clearance of molecules released during acute liver decompensation, which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy, multiple-organ failure, and other complications of liver failure. As compared to renal replacement therapies, we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems. Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging. The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins. Furthermore, conventional methods such as plasma exchange are being re-evaluated, and novel adsorption filters are increasingly being used for liver indications. These strategies are very promising for the treatment of liver failure. Nevertheless, the best method, system, or device has not been developed yet, and its probability of getting developed in the near future is also low. Furthermore, little is known about the effects of liver support systems on the overall and transplant-free survival of these patients, and further investigation using randomized controlled trials and meta-analyses is needed. This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy. It focuses on general principles of their function, and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF. In addition, we have outlined the basic advantages and disadvantages of each system.

摘要

临床上,促进急性肝衰竭(ALF)和慢加急性肝衰竭(ACLF)患者的恢复极具挑战性。尽管在理解ALF和ACLF的潜在机制方面取得了最新进展,但标准药物治疗仍然是主要的治疗方法。肝移植(LT)被认为是最后的选择,在某些情况下,它是唯一能挽救生命的干预措施。不幸的是,这种干预受到器官捐赠短缺或排除标准的限制,以至于并非所有有需要的患者都能接受移植。另一种选择是使用人工体外血液净化系统恢复受损的肝功能。首批此类系统是在20世纪末开发的,作为过渡治疗提供解决方案,无论是用于肝脏恢复还是肝移植。它们增强了对因肝功能受损而积累的代谢产物和物质的清除。此外,它们有助于清除急性肝失代偿期间释放的分子,这些分子可在这些患者中引发过度的炎症反应,导致肝性脑病、多器官衰竭和其他肝衰竭并发症。与肾脏替代疗法相比,尽管这些系统的技术有了显著发展,但我们在使用人工体外血液净化系统完全替代肝功能方面仍未成功。提取中高分子量以及疏水性/蛋白结合分子仍然极具挑战性。目前大多数可用系统包括多种方法的组合,用于清除不同范围和类型的分子及毒素。此外,诸如血浆置换等传统方法正在重新评估,新型吸附滤器越来越多地用于肝脏适应症。这些策略在治疗肝衰竭方面非常有前景。然而,尚未开发出最佳的方法、系统或设备,而且在不久的将来开发出来的可能性也很低。此外,关于肝支持系统对这些患者的总体生存率和无移植生存率的影响知之甚少,需要使用随机对照试验和荟萃分析进行进一步研究。本综述介绍了用于肝脏替代治疗的最流行的体外血液净化技术。它重点关注其功能的一般原则,以及关于它们在解毒和支持ALF和ACLF患者方面有效性的证据。此外,我们概述了每个系统的基本优缺点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4fe/10303607/3a1237bbab30/WJCC-11-3932-g001.jpg

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