Liver dialysis
Encyclopedia
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.
or liver regeneration (in the case of acute liver failure) and, unlike kidney dialysis (for renal failure
), cannot support a patient for an extended period of time (months to years).
in Germany
.It was originally produced by Teraklin AG which was acquired by Gambro
in 2004. MARS 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 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.http://www.gambro.com/upload/Press%20Releases/2005/MARS_510k.pdf Canada's first MARS unit arrived at the Toronto General Hospital
in 2005.
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.
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.
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.
Liver failure
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
and has shown promise for patients with hepatorenal syndrome
Hepatorenal syndrome
Hepatorenal syndrome is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure...
. It is similar to hemodialysis
Hemodialysis
In medicine, hemodialysis is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in renal failure. Hemodialysis is one of three renal replacement therapies .Hemodialysis can be an outpatient or inpatient therapy...
and based on the same principles. Like a bioartificial liver device
Bioartificial liver device
A bioartificial liver device is an artificial extracorporeal supportive device for an individual who is suffering from acute liver failure.-Use:...
, it is a form of artificial extracorporeal liver support
Artificial extracorporeal liver support
Artificial extracorporeal liver support is term that is used to describe measures that are used to carry-out liver function and are outside of the body.Devices that support liver function outside of the body are:*Liver dialysis*Bioartificial liver devices...
.
A critical issue of the clinical syndrome in liver failure
Liver failure
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
is the accumulation of toxins not cleared by the failing liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. Based on this hypothesis, the removal of lipophilic
Lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...
, albumin-bound substances such as bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
, bile acids, metabolites of aromatic amino acids
Aromatic amino acids
Aromatic amino acids are amino acids that include an aromatic ring.Examples include:* Among 20 standard amino acids: phenylalanine, tryptophan, and tyrosine* Others: thyroxine-See also:* Aromatic L-amino acid decarboxylase...
, 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
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
and primarily removes water soluble toxins, however it does not remove toxins bound to albumin
Human serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein...
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 transplantationLiver transplantation
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original...
or liver regeneration (in the case of acute liver failure) and, unlike kidney dialysis (for renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
), 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), has been developed at the University of RostockRostock
Rostock -Early history:In the 11th century Polabian Slavs founded a settlement at the Warnow river called Roztoc ; the name Rostock is derived from that designation. The Danish king Valdemar I set the town aflame in 1161.Afterwards the place was settled by German traders...
in Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
.It was originally produced by Teraklin AG which was acquired by Gambro
Gambro
Gambro is a global medical technology companythat manufactures products for Dialysis treatment.The company is a global leader in developing, manufacturing andsupplying products and therapies for Kidneyand Liver Dialysis, Myeloma Kidney Therapy, and other...
in 2004. MARS 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
Human serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein...
, 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
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
, bile acids, bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
, copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
, iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
and phenols
Phenols
In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of a hydroxyl group bonded directly to an aromatic hydrocarbon group...
.
MARS has 510 (k) approval from the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) for drug overdoses and poisoning as of June 2005 and is available in the USA since the end of 2005.http://www.gambro.com/upload/Press%20Releases/2005/MARS_510k.pdf Canada's first MARS unit arrived at the Toronto General Hospital
Toronto General Hospital
The Toronto General Hospital , is a part of the University Health Network, and a major teaching hospital in downtown Toronto, Ontario. It is located in the Discovery District, directly north of the Hospital for Sick Children, across Gerrard Street West, and east of Princess Margaret Hospital and...
in 2005.
Single Pass Albumin Dialysis (SPAD)
Single pass albumin dialysis (SPAD) is a simple method of albuminHuman serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein...
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 vitroIn vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
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
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
reduction than MARS. Bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
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
Human serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein...
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.
Prometheus
The Prometheus system (FreseniusFresenius AG
Fresenius SE & Co. KGaA is a globally diversified health care company based in Bad Homburg, Germany.The Fresenius Group provides products and services for dialysis, hospitals as well as inpatient and outpatient medical care...
Medical Care, Bad Homburg
Bad Homburg
Bad Homburg vor der Höhe is the district town of the Hochtaunuskreis, Hesse, Germany, on the southern slope of the Taunus, bordering among others Frankfurt am Main and Oberursel...
, Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
) is a new device based on the combination of albumin
Human serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein...
adsorption
Adsorption
Adsorption is the adhesion of atoms, ions, biomolecules or molecules of gas, liquid, or dissolved solids to a surface. This process creates a film of the adsorbate on the surface of the adsorbent. It differs from absorption, in which a fluid permeates or is dissolved by a liquid or solid...
with high-flux hemodialysis
Hemodialysis
In medicine, hemodialysis is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in renal failure. Hemodialysis is one of three renal replacement therapies .Hemodialysis can be an outpatient or inpatient therapy...
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
Hepatorenal syndrome
Hepatorenal syndrome is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure...
(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.
See also
- American Society for Artificial Internal OrgansAmerican Society for Artificial Internal OrgansAmerican Society for Artificial Internal Organs is an organization of individuals and groups that are interested in artificial internal organs and their development....
and European Society for Artificial Organs - Artificial extracorporeal liver supportArtificial extracorporeal liver supportArtificial extracorporeal liver support is term that is used to describe measures that are used to carry-out liver function and are outside of the body.Devices that support liver function outside of the body are:*Liver dialysis*Bioartificial liver devices...
- Bioartificial liver deviceBioartificial liver deviceA bioartificial liver device is an artificial extracorporeal supportive device for an individual who is suffering from acute liver failure.-Use:...
External links
- 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 Artificial Organs (ESA0)
- Information on different Liver Dialysis Systems
MARS
- Gambro - the manufacturer of MARS.
- MARS - Molecular Adsorbent Recycling System - a description of MARS.
- MARS-Leberdialyse - has a picture of 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
SPAD
- 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
Prometheus
- Fresenius Medical Care - Manufacturer 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