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生物人工肝支持治疗暴发性肝衰竭

Bioartificial liver support for fulminant hepatic failure.

作者信息

Anand A C

机构信息

Department of Gastroenterology, Army Hospital R & R, New Delhi.

出版信息

Indian J Gastroenterol. 2003 Dec;22 Suppl 2:S69-74.

Abstract

Mortality from fulminant hepatic failure (FHF) is high (50%-80%), although survivors have absolutely normal liver function. The only treatment option that is curative is liver transplantation. However, because of shortage of cadaveric organ donors and/or delay in their availability, only 10% of FHF patients ultimately receive a transplant. This has led to development of artificial liver support systems with an idea to bridge the time to transplantation and/or recovery from FHF. Initial support systems were based on the principles of hemodialysis, hemofiltration, plasma-exchange, and hemoperfusion through adsorbent media (e.g., charcoal). However, lack of clinical efficacy, problems of bioincompatibility and fear of loss of circulating hepatocyte-regeneration factors led to the search for alternate strategies. With the successful long-term propagation and culturing of human and pig hepatocytes, and the development of adequate biocompatible microcarrier modules, it is now possible to achieve sufficient density of hepatocytes per unit volume to develop bioartificial liver systems. These can be implanted transperitoneally but are subject to early destruction because of inadequate vascularization and immune attack from the host. Thus the major thrust is now to develop bioreactors, e.g., Extracorporeal Liver Assist Device (ELAD), Bioartificial Liver (BAL), etc. These contain human or pig hepatocytes implanted on hollow-fiber ultrafiltration cartridges. The patient's blood or plasma circulates through these bioreactors and after clearance of toxic compounds (via ultrafiltration and metabolism in hepatocytes) and addition of synthesized products, is returned to the patient. This article reviews the genesis, the pros and cons, and the clinical experience of BAL support for FHF.

摘要

暴发性肝衰竭(FHF)的死亡率很高(50%-80%),尽管幸存者的肝功能完全正常。唯一具有治愈性的治疗选择是肝移植。然而,由于尸体器官供体短缺和/或其可用性延迟,只有10%的FHF患者最终接受移植。这促使了人工肝支持系统的发展,其目的是在等待移植和/或从FHF恢复的过程中起到过渡作用。最初的支持系统基于血液透析、血液滤过、血浆置换以及通过吸附介质(如木炭)进行血液灌流的原理。然而,由于缺乏临床疗效、生物不相容性问题以及担心循环中的肝细胞再生因子丢失,人们开始寻找替代策略。随着人类和猪肝细胞的长期成功繁殖和培养,以及合适的生物相容性微载体模块的开发,现在有可能在每单位体积中实现足够密度的肝细胞,从而开发生物人工肝系统。这些系统可以经腹腔植入,但由于血管化不足和宿主的免疫攻击,容易早期被破坏。因此,目前的主要研究方向是开发生物反应器,例如体外肝辅助装置(ELAD)、生物人工肝(BAL)等。这些生物反应器包含植入中空纤维超滤柱上的人或猪肝细胞。患者的血液或血浆通过这些生物反应器循环,在清除有毒化合物(通过超滤和肝细胞代谢)并添加合成产物后,再返回给患者。本文综述了BAL支持FHF的起源、优缺点及临床经验。

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