Biological Extracorporeal Liver Assist Devices: A minireview (January 13, 2005)

This article reviews the growth of Biological Extracorporeal Liver Assist Devices (ELAD) as an alternative to traditional organ transplantation that has been the primary method of treating chronic liver failure in past decades. However, due to the decreasing number of organ donors, high costs, high morbidity and the need to be on lifelong immunosuppressive drugs, research in ELADs could yield wider applications of the ELAD to the general public.

A scary figure from the article is that up to 90% of patients with FHF (fulminant hepatic failure) develop irreversible neurologic damage, multiple organ failure, or sepsis while waiting for a liver transplant. The liver does have the ability to regenerate and repair, but this ability is impaired after liver damage. Recently, the artificial liver development has advanced with the use of live hepatocytes and new biomaterials. Similar to the collagen of the heart being used as a scaffold for stem cells to grow, hepatocytes cooperate with the biomaterials to act as a functioning artificial liver.

Most studies in the field targeted blood detoxification and used techniques like hemodialysis and plasma exchange. None of these were shown to improve patient survival. The extracorporeal liver (ELAD) assist device was developed that used whole blood perfusion through a bioreactor with a human hepatoblastoma cell line. A study noted no significant effect on disease outcome. Another device developed in Germany is the modular extracorporeal liver system (MELS). It had a multicompartment bioreactor and capillary systems to perform functions such as cell oxygenation and carbon dioxide removal. The MELS system uses human liver cells harvested from organs unsuitable for transplant. Surprisingly, it maintained hepatocyte functions for longer than 2 months and a clinical study is in progress.

The authors themselves have created a hybrid BAL system, HepatAssist System, using cryopreserved porcine hepatocytes that is the first cell-based device in a phase II/III clinical trial and has been successful in treating acute liver failure and bridging patients until transplantation.

I am concerned of the possibilty of viral infection from pig to human tissues. There are also concerns about how and where hepatocytes are harvested from, storage, and how many hepatocytes are adequate for liver function. The variability in the different models are based on these factors as well as the actual materials used for the hollow fibers and bioreactor. With the health care reform, there is a possibility that more funding will be provided for this research in order to find a device that can be used as a basic model for all companies. Granted there would be increased competition between different companies to build the first successfully FDA-approved model, but once it is created they could cooperate in order to increase efficiency of the original design and make the artificial liver more accessible as a public option for acute and chronic liver failure

-Robin

Nozomu Sugiyama, Transplantation Reviews, July 2001

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