assist device (ELAD), was developed by Sussman et al. 6 Cells The objective of this pilot controlled study was to evalderived from a human hepatoblastoma cell line (C3A) are uate the extracorporeal liver assist device (ELAD) in pacultured within the extracapillary space of a dialysis cartients with acute liver failure who were judged to still tridge. Whole blood is used for the perfusion 7 and, unlike the have a significant chance of survival (Ç50%) and in those BAL where plasma perfusion is limited to 6 hours, ELAD who had already fulfilled criteria for transplantation.support can be continued for long periods of time. 8 In early Twenty-four patients were divided into two groups, 17 experimental work in anhepatic dogs, function of the device with a potentially recoverable lesion (group I) and 7 was deduced from the requirement for further anaesthesia, listed for transplantation (group II), and then randomly changes in plasma ammonia level, and length of survival. allocated to ELAD haemoperfusion or control. The meSmall amounts of human albumin were also detected in the dian period of ELAD haemoperfusion was 72 hours circulation which peaked after 7 hours of haemoperfusion. 9 (range 3-168 h). Biocompatibility of the device was good,In further studies performed in a canine model of ALF inwith no acceleration in platelet consumption, and duced by acetaminophen toxicity, 10 80% of treated animals haemodynamic stability was maintained. Two patients survived as compared with none of the controls. 11 In addition were withdrawn from the study because of worsening the extent of liver injury, assessed both histologically and of preexisting disseminated intravascular coagulation from the serum alanine transaminase, appeared to be less in in one case and a hypersensitivity reaction in the other.the haemoperfused animals. 6 An initial case report of the use Deterioration with respect to encephalopathy grade was of the ELAD included one patient who recovered from acute more frequent in the control patients, 7 of 12 (58%), than liver failure secondary to syncytial giant cell hepatitis, 12 and in the ELAD-treated patients, 3 of 12 (25%). In group I in the first clinical series of cases, mental status was imwhere survival for the ELAD cases was 7 of 9 (78%), there proved in 8 of the 11 patients, 4 of whom were transplanted, was a higher than expected survival in the controls, 6although only 1 case survived. 8 of 8 (75%). For group II cases, survival was 1 of 3 (33%)The objective of the present pilot but controlled study was for the ELAD-treated patients, and 1 of 4 (25%) for the to assess use of the ELAD device in two groups of patients, controls. Both of the survivors underwent transplantathose in whom there was judged to be some potential for tion. Assessment of additive function for the device rerecovery and those affected to a greater extent where it is vealed an improvement in galactose elimination capacused as a bridge to transplantation. Particular attention was ity after 6 hours of haemoperfusion. Based on the results d...

No abstract

Liver transplantation is currently the only effective therapy for patients with fulminant hepatic failure. The availability of an artificial liver could bridge these patients through the relatively brief crisis period and allow their own livers to regenerate, providing a more favorable outcome and sparing the trauma and expense of transplant. We have developed a device consisting of a highly differentiated human liver cell line cultured in a hollow fiber cartridge. This device is capable of supporting dogs with acetaminophen-induced fulminant hepatic failure for a period long enough for their own livers to resume function. Even though liver function tests such as albumin and prothrombin time became extremely abnormal during the course of the experiment, the dogs did not become encephalopathic. Two of the three treated animals recovered sufficient liver function after 42 to 48 hr of treatment that they could be disconnected from the device, and they survived the experiment. Histological results and serum ALT levels suggest that the device affected the course of the disease in two animals, allowing recovery of hepatocytes that would otherwise have lysed. In the third animal, regenerative nodules demonstrated that, even in the presence of severe liver injury, the device was capable of supporting total liver function.

Eleven patients were treated with the Hepatix extracorporeal liver assist device (ELAD) between June 1991 and August 1993. The first 2 patients were treated according to Food and Drug Administration guidelines ("Emergency Use of Unapproved Medical Devices," October 22, 1985), and the remaining 9 were treated according to an Investigational Device Exemption (IDE). The goal of the study was to establish the short-term safety of ELAD therapy, with a focus on acute medical complications such as hemodynamic instability, complement activation, and deterioration of vital organ function. As secondary goals, the metabolic capacity of ELAD cartridges and their clinical impact were assessed. Treatment was considered successful if the patient recovered sufficient liver function to survive weaning from the ELAD or was stabilized until orthotopic liver transplantation was performed. No short-term safety problems were associated with ELAD use. In addition, metabolic support was documented in 10 of the 11 patients, and 6 patients reached a successful end-point. The Hepatix ELAD is safe, and it provides measurable metabolic support in patients with late-stage liver failure. This pilot study provides the impetus to perform controlled trials of ELAD therapy in the treatment of various types of end-stage liver disease.

In stark contrast to short-term survival, there have been no appreciable improvements in long-term survival following liver transplantation among 1-year survivors. Long-term sequelae of immunosuppression, including malignancy and infection, are the most common causes of death. This study highlights the need for better long-term immunosuppression management.