Koebe H G, Schildberg F W
Chirurgische Universitätsklinik und Poliklinik, Ludwig-Maximilians-Universität, München, Bundesrepublik Deutschland.
Wien Klin Wochenschr. 1998 Sep 4;110(16):551-63.
A Bioartificial Liver (BAL) is not available to date. Human therapeutic applications of different systems of BAL as of 1998 are presented and discussed. It is concluded that--as for now--no artificial liver device has gained any importance for the treatment of liver failure, and that some critical issues in this field of research have not been sufficiently investigated and/or are not resolved. This review analyzes reports of clinical applications of BAL from the following research groups (numbers in brackets indicate patients treated with an artificial liver device): Demetriou/Rozga, Los Angeles (31 patients), Williams, London (1 patient); Gerlach, Berlin (1 patient); Strom, Virginia (5 patients). The BAL systems used in these studies cannot be directly compared because there are considerable differences in the quality and in quantity of the functional unit employed in bioreactors, the experimental design, patient selection, to mention just a few points. None of the systems investigated so far could convincingly prove its effectivity in replacing impaired liver function neither in animal models nor in a clinical application. It remains to be shown, whether liver cells cultured in bioreactors remain stable, i.e. viable and functionally active, for a sufficient period of treatment. Selected metabolic or detoxifying functions of the bioreactor are difficult to assess, since these functions do not necessarily serve as pars pro toto for the complex clinical presentation of liver failure and therefore cannot sufficiently validate any organ replacement system. Furthermore, since some applications combine biological units with other components, such as active charcoal, it be-comes even more difficult to assess the role of hepatocytes in these settings. Case reports of patients treated with BAL usually refer to BAL as a "successful bridge to transplant", thereby demonstrating the positive effect of orthotopic/auxiliary liver transplants in the treatment of acute liver failure rather than the potential benefit derived from an artificial liver device. Randomised studies have been proposed and urged for years in order to prove the effectivity of these systems which, in part, are already available for clinical use. Because of the heterogeneous patient group in question the design of such protocols will be a difficult task. It must be asked, whether currently used artificial liver systems have left basic science research too early; the use of "black box" applications in humans cannot draw its legitimation merely from the fact that an effective conservative treatment of liver failure is not available so far.
生物人工肝（BAL）目前尚未问世。本文介绍并讨论了截至1998年不同生物人工肝系统在人体治疗中的应用情况。结论是，就目前而言，尚无任何人工肝装置在治疗肝衰竭方面具有重要意义，且该研究领域的一些关键问题尚未得到充分研究和/或解决。本综述分析了以下研究小组关于生物人工肝临床应用的报告（括号内数字表示接受人工肝装置治疗的患者数量）：洛杉矶的德米特里乌/罗兹加小组（31例患者）、伦敦的威廉姆斯小组（1例患者）、柏林的格拉赫小组（1例患者）、弗吉尼亚的斯特罗姆小组（5例患者）。这些研究中使用的生物人工肝系统无法直接进行比较，因为生物反应器中所采用功能单元的质量和数量、实验设计、患者选择等方面存在相当大的差异，仅举这几点为例。到目前为止，所研究的任何系统都未能在动物模型或临床应用中令人信服地证明其在替代受损肝功能方面的有效性。生物反应器中培养的肝细胞在足够长的治疗期间内是否保持稳定，即是否存活且功能活跃，仍有待证实。生物反应器选定的代谢或解毒功能难以评估，因为这些功能不一定能代表肝衰竭复杂临床表现的整体情况，因此无法充分验证任何器官替代系统。此外，由于一些应用将生物单元与其他成分（如活性炭）结合使用，在这些情况下评估肝细胞的作用变得更加困难。接受生物人工肝治疗患者的病例报告通常将生物人工肝称为“成功的移植桥梁”，从而证明原位/辅助肝移植在治疗急性肝衰竭中的积极作用，而非人工肝装置的潜在益处。多年来一直有人提议并敦促进行随机研究，以证明这些部分已可供临床使用的系统的有效性。由于相关患者群体的异质性，此类方案的设计将是一项艰巨任务。必须要问的是，目前使用的人工肝系统是否过早地脱离了基础科学研究；在人体中使用“黑箱”应用不能仅仅因为目前尚无有效的肝衰竭保守治疗方法就获得其合理性。
