SBIR-STTR Award

Orthotopic liver transplantation is an effective and increasingly popular therapy for a variety of liver diseases but there is as yet no method for temporarily sustaining a patient awaiting transplant who enters into hepatic failure. C3A is a human liver cell line derived from an hepatoblastoma that retains most of the characteristics of the human hepatocyte. We have cultured these cells in hollow fiber devices and shown that they are capable of carrying out many of the major liver-specific metabolic interconversions. We have successfully tested this device in an animal model of fulminant hepatic failure and in four human subjects. In preparation for a multisite trial of this device, we will undertake a feasibility study of five patients gathered from the affiliated hospitals of the Baylor College of Medicine and at the Hermann Hospital, Univ. of Texas School of Medicine. The use of liver transplantation is limited by both the availability of organs and financial constraints. An ELAD should have application in a number of transplant situations. First, it will allow patients in fulminant hepatic failure to be stabilized and calmly evaluated before operating. Second, it will find use in stabilizing and assisting patients after transplant, particularly in situations in which the graft fails on reperfusion. Third, in some instances, it may serve as a substitute for transplant. This device would allow time for the patient's natural liver to regenerate, sparing the expense of operation, the lifelong dependence on immunosuppression and the likelihood of premature mortality.Awardee's statement of the potential commercial applications of the research: There are currently about 300 liver transplantations being performed per Year in both the United States and Europe. It is estimated that this is only 10-20% of the total population who need additional liver function but who for financial or health reasons are not eligible for transplant. Estimates of the market size, where an ELAD available, range from $25 million for transplant use only to $300 million if the device is employed in less critical situations, such as in chronic liver disease.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Excepting liver transplantation, there is as yet no widely available method for temporarily sustaining a patient who enters into hepatic failure. We have developed an extracorporeal liver assist device (ELAD) using a cloned human liver cell line and shown that it is capable of carrying our many of the major liver-specific metabolic inter-conversions. We have successfully tested this device in an animal model of fulminant hepatic failure and in sixteen human subjects to determine safety. Hepatix proposes to carry out a multisite, randomized control trial of this device to ascertain its effectiveness in treating fulminant hepatic failure. This trial will be carried out at several of the major liver centers in the United States and will be the first large scale study of fulminant hepatic failure in this country. As part of the study, we propose to collect and analyze samples from each patient in an attempt to define some prognostic features in the progression of fulminant hepatic failure. If the trial is successful, the data will be used to support an application to the US food and Drug Administration to market the ELAD in the United States. The ELAD will not only be the first non- surgical therapy for end stage liver disease, it will be the first commercially available device where live human cells are used in a therapeutic situation.