Liver support technology--an update.

Abstract

BACKGROUND: Currently, there is no direct treatment for hepatic failure, and patients must receive a transplant or endure prolonged hospitalization, with significant morbidity and mortality. Because of the scarcity of donor organs, liver support strategies are being developed with the aim of either supporting patients with borderline functional liver cell mass until an appropriate organ becomes available for transplantation or until their livers recover from injury. METHODS: A literature review was performed using MEDLINE and library searches. Only major blood detoxification/purification devices and cell-based techniques are included in this review. RESULTS: Currently, a number of blood purification systems and devices utilizing viable liver cells are in various stages of clinical development. Non-biological systems include plasma exchange, albumin dialysis, hemo(dia)filtration, and sorbent-based devices (charcoal, resin). These systems are able to remove toxins of hepatic failure, and their utility is limited by their inability to provide missing liver-specific functions. In contrast, hepatocyte-based devices are able to provide whole liver functions, including detoxification, biosynthesis, and biotransformation. Molecular adsorbent recycling system (MARS) blood detoxification system has been tested in thousands of patients, but additional well-conducted controlled studies are warranted to better define the role of MARS in the treatment of patients with acute hepatic failure and acute exacerbation of chronic liver disease. HepatAssist was tested in a phase II/III controlled clinical trial that demonstrated safety and proof of concept for use of biological liver support systems to improve patient survival in acute hepatic failure. CONCLUSIONS: Developing an effective liver assist technology has proven difficult, because of the complexity of liver functions that must be replaced, as well as heterogeneity of the patient population. Non-biological systems may have a role in the treatment of specific forms of liver failure where the primary goal is to provide blood detoxification/purification. Biological systems appear to be useful in treating liver failure where the primary objective is to provide whole liver functions which are impaired or lost. It is suggested that there will be a role for hybrid liver support systems that offer liver cell therapy and various forms of blood purification (sorption, hemofiltration and diafiltration) to treat patients with specific forms of liver failure at various stages of their illness.