ARTIFICIAL LIVER SUPPORT - A STATUS-REPORT

A Bioartificial Liver (BAL) is not available to date. Human therapeuti c applications of different systems of BAL as of 1998 are presented an d discussed. It is concluded that - as for now - no artificial liver d evice has gained any importance for the treatment of liver failure, an d that some critical issues in this field of research have not been su fficiently investigated and/or are not resolved. This review analyzes reports of clinical applications of BAL from the following research gr oups (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 pa tients). The BAL systems used in these studies cannot be directly comp ared because there are considerable differences in the quality and in quantity of the functional unit employed in bioreactors, the experimen tal design, patient selection, to mention just a few points. None of t he systems investigated so far could convincingly prove its effectivit y in replacing impaired liver function neither in animal models nor in a clinical application. It remains to be shown, whether liver cells c ultured in bioreactors remain stable, i.e. viable and functionally act ive, for a sufficient period of treatment. Selected metabolic or detox ifying functions of the bioreactor are difficult to assess, since thes e functions do not necessarily serve as pars pro tote for the complex clinical presentation of liver failure and therefore cannot sufficient ly validate any organ replacement system. Furthermore, since some appl ications combine biological units with other components, such as activ e charcoal, it be-comes even more difficult to assess the role of hepa tocytes in these settings. Case reports of patients treated with BAL u sually refer to BAL as a ''successful bridge to transplant'', thereby demonstrating the positive effect of orthotopic/auxiliary liver transp lants in the treatment of acute liver failure rather than the potentia l benefit derived from an artificial liver device, Randomised studies have been proposed and urged for years in order to prove the effectivi ty of these systems which, in part, are already available for clinical use. Because of the heterogenous 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 resea rch too early; the use of ''black box'' applications in humans cannot draw its legitimation merely from the fact that an effective conservat ive treatment of liver failure is not available so far.