What is Liver Dialysis?
Liver dialysis is a detoxification treatment for liver failure and has shown promise for patients with hepatorenal syndrome. It is similar to hemodialysis and based on the same principles. Like a bioartificial liver device, it is a form of artificial extracorporeal liver support.
A critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver. Based on this hypothesis, the removal of lipophilic, albumin-bound substances such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty acids and cytokines should be beneficial to the clinical course of a patient in liver failure. This led to the development of artificial filtration and adsorption devices.
Hemodialysis is used for renal failure and primarily removes water soluble toxins, however it does not remove toxins bound to albumin that accumulate in liver failure.
Liver dialysis prognosis/survival
Whilst the technique is in its infancy, the prognosis of patients with liver failure remains guarded. Liver dialysis, currently, is only considered to be a bridge to transplantation or liver regeneration (in the case of acute liver failure)123 and, unlike kidney dialysis (for renal failure), cannot support a patient for an extended period of time (months to years).
Liver dialysis devices
Artificial detoxification devices currently under clinical evaluation include the Molecular Adsorbent Recirculating System (MARS), Single Pass Albumin Dialysis (SPAD) and the Prometheus system.
Molecular Adsorbents Recirculation System (MARS)
The Molecular Adsorbents Recirculation System (MARS), developed by Teraklin AG of Germany, is the best known extracorporal liver dialysis system and has existed for approximately ten years. It consists of two separate dialysis circuits. The first circuit consists of human serum albumin, is in contact with the patient’s blood through a semipermeable membrane and has two special filters to clean the albumin after it has absorbed toxins from the patient’s blood.
The second circuit consists of a hemodialysis machine and is used to clean the albumin in the first circuit, before it is recirculated to the semipermeable membrane in contact with the patient’s blood. The MARS system can remove a number of toxins, including ammonia, bile acids, bilirubin, copper, iron and phenols.
MARS development started at the University of Rostock in Germany. It has 510 (k) approval from the Food and Drug Administration (FDA) for drug overdoses and poisoning as of June 2005 and is available in the USA since the end of 2005.1 Canada’s first MARS unit arrived at the Toronto General Hospital in 2005.
Single Pass Albumin Dialysis (SPAD)
Single pass albumin dialysis (SPAD) is a simple method of albumin dialysis using standard renal replacement therapy machines without an additional perfusion pump system: The patient’s blood flows through a circuit with a high-flux hollow fiber hemodiafilter, identical to that used in the MARS system.
The other side of this membrane is cleansed with an albumin solution in counter-directional flow, which is discarded after passing the filter. Hemodialysis can be performed in the first circuit via the same high-flux hollow fibers.
Comparing SPAD, MARS and CVVHDF
SPAD, MARS and continuous veno-venous haemodiafiltration (CVVHDF) were compared in vitro with regard to detoxification capacity. SPAD and CVVHDF showed a significantly greater reduction of ammonia compared with MARS. No significant differences could be observed between SPAD, MARS and CVVHDF concerning other water-soluble substances.
However, SPAD enabled a significantly greater bilirubin reduction than MARS. Bilirubin serves as an important marker substance for albumin-bound (non water-soluble) substances.
Concerning the reduction of bile acids no significant differences between SPAD and MARS were seen. It was concluded that the detoxification capacity of SPAD is similar or even higher when compared with the more sophisticated, more complex and hence more expensive MARS.
As albumin dialysis is a costly procedure, financial aspects are important: For a seven-hour treatment with MARS, approximately € 300 for 600 ml human serum albumin solution (20%), € 1740 for a MARS treatment kit and € 125 for disposables used by the dialysis machine have to be spent.
The cost of this therapy adds up to approximately € 2165. Performing SPAD according to the protocol by Sauer et al., however, requires 1000 ml of human albumin solution (20%) at a cost of € 500. A high-flux dialyzer costing approximately € 40 and the tubings (€ 125) must also be purchased.
The overall costs of a SPAD treatment is approximately € 656 – 30% of the costs of an equally efficient MARS therapy session. The expenditure for the MARS monitor necessary to operate the MARS disposables is not included in this calculation.
The Prometheus system (Fresenius Medical Care, Bad Homburg, Germany) is a new device based on the combination of albumin adsorption with high-flux hemodialysis after selective filtration of the albumin fraction through a specific polysulfon filter (AlbuFlow). It has been studied in a group of eleven patients with hepatorenal syndrome (acute-on-chronic liver failure and accompanying renal failure).
The treatment for two consecutive days for more than four hours significantly improved serum levels of conjugated bilirubin, bile acids, ammonia, cholinesterase, creatinine, urea and blood pH. Prometheus was proven to be a safe supportive therapy for patients with liver failure.
O’grady J. Personal view: current role of artificial liver support devices. Aliment Pharmacol Ther. 2006 Jun 1;23(11):1549-57. PMID 16696802.
van de Kerkhove MP, Hoekstra R, Chamuleau RA, van Gulik TM. Clinical application of bioartificial liver support systems. Ann Surg. 2004 Aug;240(2):216-30. PMID 15273544. Free Full Text.
Neuberger J. Prediction of survival for patients with fulminant hepatic failure. Hepatology. 2005 Jan;41(1):19-22. PMID 15690476.
Sauer IM, Goetz M, Steffen I, Walter G, Kehr DC, Schwartlander R, Hwang YJ, Pascher A, Gerlach JC, Neuhaus P.: In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD). Hepatology. 2004 May;39(5):1408-14. PMID 15122770
^ Rifai K, Ernst T, Kretschmer U, Bahr MJ, Schneider A, Hafer C, Haller H, Manns MP, Fliser D. Prometheusa new extracorporeal system for the treatment of liver failure. J Hepatol. 2003 Dec;39(6):984-90. PMID 14642616.
American Society for Artificial Internal Organs and European Society for Artificial Organs
Artificial extracorporeal liver support
Bioartificial liver device
Sen S, Williams R, Jalan R. Emerging indications for albumin dialysis. Am J Gastroenterol. 2005 Feb;100(2):468-75. Review. PMID 15667509
Liver Support Working Group of the European Society for Artficial Organs (ESA0)
Information on different Liver Dialysis Systems
Gambro – the manufacturer of the MARS.
MARS – Molecular Adsorbent Recycling System (Teraklin) – a description of the MARS.
MARS-Leberdialyse – has a picture of the MARS in action.
Evenepoel P, Maes B, Wilmer A, Nevens F, Fevery J, Kuypers D, Bammens B, Vanrenterghem Y. Detoxifying capacity and kinetics of the molecular adsorbent recycling system. Contribution of the different inbuilt filters. Blood Purif. 2003;21(3):244-52. PMID 12784051
Mitzner S, Klammt S, Stange J, Noldge-Schomburg GF, Schmidt R. [Extracorporeal blood purification in severe liver failure with the albumin dialysis MARS impact on relevant intensive care parameters] Anasthesiol Intensivmed Notfallmed Schmerzther. 2005 Apr;40(4):199-206. PMID 15832238
Artificial Liver Support Systems – Charité Berlin – Campus Virchow – Division of Experimental Surgery and Regenerative Medicine – gives detailed descriptions on artificial and bioarticial liver support concepts and – in particular – on SPAD
Modular Extracorporeal Liver Support (MELS) – Charité Berlin – Campus Virchow – Division of Experimental Surgery and Regenerative Medicine
Fresenius Medical Care – Manufactor of the Prometheus system
The Prometheus System – Product description with pictures of the system
The Prometheus System – Development of an Adsorptive Blood Purification System called Prometheus – Donau-Universität Krems