Bioartificial livers are extracorporeal [outside body] devices embedded hepatocytes (liver cells) that are used to perform the functions of a normal liver.
The first bioartificial liver (BAL) device was developed by Dr. Kenneth Matsumara in 2001. Several types of BALs are being developed. The bioartificial liver support in combination with artificial devices is promising but has several challenging tasks.
The ideal device is still underdeveloped and the different available devices are in different stages of trials.
Modern bioartificial liver devices have liver cells suspended in a solution and the patient’s blood is processed by a semipermeable membrane that allows toxins and blood proteins to pass but restricts an immunological response.
Various cell sources used for living cells in the bioartificial liver are primary porcine hepatocytes, primary human hepatocytes, human hepatoblastoma (C3A) cell lines, immortalized human cell lines and stem cells
There are currently several BAL devices in clinical trials.
Bioartificial Liver Device Vs Artificial Liver Support
Artificial liver support devices are nonbiologic extracorporeal liver support systems that aim at temporary liver support until a suitable donor liver is found.
In the past, techniques such as hemodialysis, hemofiltration, charcoal hemoperfusion, plasmapheresis, and exchange transfusions, have been used but no controlled study has shown long-term benefit.
Molecular adsorbent recirculating system (MARS) is the most extensively investigated liver support system. In this device, blood is dialyzed across an albumin-impregnated membrane against 20% albumin. Charcoal and anion exchange resin columns in the circuit cleanse and regenerate the albumin dialysate.
This system has been shown in the studies to improve hyperbilirubinemia and hepatic encephalopathy.
Prometheus device is a system that uses the principle of fractionated plasma separation and adsorption. It is based on fractional plasma separation and adsorption, and hemodialysis. It has been shown that it is effective in the removal of various toxins without any adverse events.
Single-pass albumin dialysis is another artificial liver support device, that like the previous two systems, is based on the removal of albumin-bound toxins. The patient’s blood also passes a high flux dialysis membrane. Albumin solution streams along the other side of the membrane counter-directionally, accepting toxins from the plasma.
Selective plasma filtration therapy using a single-use cartridge containing hollow is also under trial.
Currently available liver support systems are not routinely recommended outside of clinical trials.
Till now, artificial liver support has shown good results in excretory and to some extent regulatory functions but lacks synthetic functions of the liver which can only be provided by living cells.
Need for Bioartificial Liver
The purpose of bioartificial liver type devices is to serve as a supportive device, either allowing the liver to regenerate properly upon acute liver failure, or to bridge the individual’s liver functions until a transplant is possible.
Liver failure constitutes a life-threatening condition and can, in most cases, only be overcome by orthotopic liver transplantation. This led to the development of various artificial and bioartificial liver support devices.
The liver is a complex organ with various vital functions.
The liver is involved in the synthesis, detoxification and regulation of various products and its failure is life-threatening.
Read more| Acute liver failure
There is a high mortality associated with liver failure and the only definitive treatment that reduces mortality is liver transplantation.
But many people may not survive until a suitable donor organ is available due to the rarity of donor organ available.
In certain other cases, liver transplantation is not feasible.
Extracorporeal liver assist devices i.e artificial liver and biological liver are used to buy the time while waiting for transplantation. These can also be used to provide temporary support to the failing organ until it is able to regenerate.
While artificial liver devices are able to carry detoxification and to some extent regulation, they cannot provide synthetic functions.
The synthetic function of the liver can only be provided by living cells. Bioartificial liver devices were developed to provide synthetic functions by inculcating living cells in them.
Bioartificial Liver Devices
Bioartificial systems were developed to take over partially the synthetic and regulatory function of the liver besides detoxifying the patient’s plasma. Different cell sources are primary cells, either human or animal origin, tumor cells, and expandable progenitor cell populations.
Primary human cells are most compatible. These cells are usually isolated from donor organs rejected for transplantation.
Xenogeneic cells or cells of animal origin are usually taken from pig liver. These cells are easily available but compatibility is not assured. In addition, there is a risk of transmission of infection and metastatic cells.
Due to these, the ideal source would probably be human progenitor cells but developing a significant mass is still a challenge.
CellModule system consists of three interwoven hollow fiber bundles which are embedded in a polyurethane housing. It is part of the Modular Extracorporeal Liver Support (MELS) device and can be combined with continuous venovenous haemodiafiltration and albumin dialysis. Earlier porcine cells were used but now primary human cells are preferred.
In trials, it has led to successful bridging to transplantation.
AMC-BAL [Academisch Medisch Centrum Amsterdam Bioartificial Liver] consists of an extracorporeal bioreactor placed in BAL-module. Its configuration is a three-dimensional, nonwoven, hydrophilic polyester matrix rolled like a mat with oxygen-carrying fibers in between. Oxygenation capillaries are incorporated by the matrix to provide local oxygenation. During therapy, the patient’s plasma is directly perfused through the matrix, so this system features only one membrane barrier. It uses porcine cells.
Extracorporeal Liver Assist Device (ELAD) utilizes C3A cells, a cell line derived from the human hepatoblastoma cell line HepG2. The cells are localized in the extracapillary space of a modified dialysis cartridge. Two additional filters are used to ensure the filtering of tumor cells.
HepatAssist is another device that uses porcine liver cells that are located in the extracapillary space of a modified dialysis cartridge. The patient’s plasma is led through the bioreactor after passing an active charcoal filter and an oxygenator first.
Limitations of Bioartificial Liver Device
In most bioartificial liver support devices, the liver cells are separated from the patient’s blood or plasma by at least one membrane to provide an immunological barrier.
But it also limits the exchange of substances and therefore potentially reduces the effectiveness of the system.
Moreover, to be effective, a minimum liver mass is necessary to provide sufficient liver function for survival. Therefore, it remains to be sufficiently answered if the 50–200 g cell mass used in most bioartificial liver devices will show a significant effect.
- Freeman JG, Matthewson K, Record CO. Plasmapheresis in acute liver failure. Int J Artif Organs. 1986;9:433–438
- Rifai K, Manns MP. Review article: Clinical experience with Prometheus. Ther Apher Dial. 2006;10:132–137.
- Sauer IM, Gerlach JC. Modular extracorporeal liver support. Artif Organs. 2002;26:703–706.
- Sauer IM, Zeilinger K, Pless G, Kardassis D, Theruvath T, Pascher A, Goetz M, Neuhaus P, Gerlach JC. Extracorporeal liver support based on primary human liver cells and albumin dialysis-treatment of a patient with primary graft nonfunction. J Hepatol. 2003;39:649–653.
- van de Kerkhove MP, Di Florio E, Scuderi V, Mancini A, Belli A, Bracco A, Scala D, Scala S, Zeuli L, Di Nicuolo G, Amoroso P, Calise F, Chamuleau RA. Bridging a patient with acute liver failure to liver transplantation by the AMC-bioartificial liver. Cell Transplant. 2003;12:563–568.
- Millis JM, Cronin DC, Johnson R, Conjeevaram H, Conlin C, Trevino S, Maguire P. Initial experience with the modified extracorporeal liver-assist device for patients with fulminant hepatic failure: System modifications and clinical impact. Transplantation. 2002;74:1735–1746.
- Hui T, Rozga J, Demetriou AA. Bioartificial liver support. J Hepatobiliary Pancreat Surg. 2001;8:1–15.
- Mullon C, Pitkin Z. The HepatAssist bioartificial liver support system: Clinical study and pig hepatocyte process. Expert Opin Investig Drugs. 1999;8:229–235.