IN-VIVO EVALUATION OF A HOLLOW-FIBER LIVER ASSIST DEVICE

Orthotopic liver transplantation is the only effective form of therapy currently available for patients with fulminant hepatic failure (FHF) . The use of an extracorporeal (EC) liver assist device (LAD) may resu lt in improved presurgical clinical management. Alternatively, patient s treated with LADs could avoid the transplantation procedure if they are able to regenerate a critical mass of hepatocytes that will sustai n functional viability. In this study, the efficacy of a prototype hol low fiber LAD seeded with rabbit hepatocytes was assessed in vivo by t he use of two different animal models: (1) normal rabbits injected wit h diazepam or lidocaine, and (2) a galactosamine (GaI)-intoxicated rab bit model of FHF. The EC LAD clearly decreased the blood levels of the two drugs and significantly generated diazepam and lidocaine metaboli tes indicating the maintenance of active P450 forms in the cellular co mponent of the devices. A 6-hour EC treatment significantly increased the survival time and delayed the onset of hepatic encephalopathy (HE) in the Gal-intoxicated rabbits, Histological evaluations of postmorte m livers showed greater hepatocyte regenerative activity in the animal s treated with hepatocyte-seeded LADs than in the two control groups, e.g., rabbits not treated or treated with unseeded devices. These find ings support the concept that a microporous hollow fiber LAD seeded wi th rabbit hepatocytes is able to sustain drug detoxication in vivo as well as to modify the course of FHF in a well-characterized animal mod el.