Chamuleau Robert A F M, Poyck Paul P C, van de Kerkhove Maarten-Paul
Department of Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Ther Apher Dial. 2006 Apr;10(2):168-74. doi: 10.1111/j.1744-9987.2006.00359.x.
Both the large variety of liver functions for maintaining body homeostasis and the proven effectivity of whole liver transplantation in the therapy of acute liver failure (ALF), are important reasons to presume that cell-free liver support systems will not be able to adequately support the failing liver. Accordingly, bioartificial liver (BAL) systems have shown their efficacy in experimental ALF models in small and large animals, and have shown to be suitable and safe in phase 1 studies in humans with ALF. However, the optimal BAL system is still under development. Important issues are the source of the cellular component and the configuration of the BAL system with regard to cell attachment, mass transfer characteristics and oxygenation at site. The deficiency of all BAL systems to excrete bile effectively is another important topic for improvement. The great challenge for the future is to develop a well-functioning and safe human hepatic cell line which can replace the widely used porcine (xenogeneic) hepatocytes. Theoretically, a combination of a cell-free liver support system and a BAL system might be optimal for the treatment of ALF patients in the near future.
肝脏具有多种维持机体稳态的功能,且全肝移植治疗急性肝衰竭(ALF)已被证实有效,这些都是推测无细胞肝支持系统无法充分支持衰竭肝脏的重要原因。因此,生物人工肝(BAL)系统在大小动物的实验性ALF模型中已显示出其疗效,并且在ALF患者的1期研究中已证明是合适且安全的。然而,最佳的BAL系统仍在研发中。重要问题包括细胞成分的来源以及BAL系统在细胞附着、传质特性和局部氧合方面的配置。所有BAL系统有效排泄胆汁的不足是另一个重要的改进课题。未来的巨大挑战是开发一种功能良好且安全的人肝细胞系,以取代广泛使用的猪(异种)肝细胞。从理论上讲,无细胞肝支持系统和BAL系统的组合在不久的将来可能是治疗ALF患者的最佳选择。