Bioartificial liver support for fulminant hepatic failure.

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.