Patients with acute liver failure (ALF) continue to have an almost 50% mortality rate despite improvements associated with the use of orthotopic liver transplantation (OLT). Numerous ex vivo methods have been developed in attempts to improve patient survival. These methods can be divided into three groups: detoxification (e.g., dialysis, charcoal adsorption, plasma exchange), which only provides excretory function; ex vivo liver perfusion (e.g., whole organ or tissue perfusion), which provides some metabolic function; and bioartificial or cell-based systems, which combine elements of the first two methods. Clinical trials have shown minimal efficacy of the various detoxification methods in terms of ALF patient survival, while the relative success of OLT has shown the importance of providing metabolic as well as excretory functions. Attempts to provide those additional functions with ex vivo tissue perfusion have been fraught with complications such as clotting and acute tissue rejection, leading to the conceptual development of cell-based bioreactor systems. A number of these bioartificial systems have been clinically evaluated, and the preliminary patient survival rates have encouraged further work in this area.

ABSTRACT. Jaundice, which is characterized by an excessive accumulation of bilirubin in the blood and tissues, occurs in 13% of newborns. The common treatments for neonatal jaundice are phototherapy and blood exchange transfusion. A novel approach using an extracorporeal blood filter containing immobilized bilirubin oxidase was recently proposed to detoxify jaundiced blood, and a prototype device markedly reduced serum bilirubin in genetically jaundiced Gunn rats. The primary toxicologic effect in that study was a 20% reduction in red blood cell count. Using a compartmental model for bilirubin metabolism, a mathematical simulation of the extracorporeal treatment's ability to reduce serum bilirubin levels in jaundiced infants is presented. Using a 10-mL reactor volume containing immobilized bilirubin oxidase, the simulation predicts a 32 to 65% decrease in plasma bilirubin concentration over a 4-h treatment for a 2 kg preterm hyperbilirubinemic newborn. In addition, a new approach to altering support material has essentially eliminated red blood cell lysis in vivo using Gunn rats and in vitro using adult blood. (Pediatr Res 26: [452][453][454][455][456][457] 1989)