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{{Liver dialysis}}
{{Liver dialysis}}
{{Interventions infobox |
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  ICD10      = |
  ICD9        = 50.92 |
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'''This article specifically discusses liver dialysis. For information regarding kidney dialysis or dialysis in general, please click [[Dialysis|here]].
'''This article specifically discusses liver dialysis. For information regarding kidney dialysis or dialysis in general, please click [[Dialysis|here]].'''


==Overview==
==Overview==
'''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]].
Liver dialysis is a type of [[artificial extracorporeal liver support]]. It is a new promising emerging therapeutic technique used for the detoxification treatment for liver failure and it has shown positive impact on the outcomes of [[hepatorenal syndrome]]. Liver dialysis follows the same principles of [[hemodialysis]]. The concerning matter during a liver failure is the accumulation of toxins in the blood stream which are not cleared by an injured liver. Based on this hypothesis, the elimination of albumin-bound substances such as [[bilirubin]], [[Bile acid|bile acids]], metabolites of [[aromatic amino acids]], medium-chain [[fatty acids]] and [[cytokines]] has led to the invention of artificial filtration and adsorption devices. Several new devices are invented for this purpose such as Molecular Adsorbent Recirculating System (MARS), Single Pass [[Albumin]] Dialysis (SPAD), Prometheus system and DIALIVE. [[Hemodialysis]] is used for [[renal failure]] which mainly eliminates water soluble toxins, but it can not eliminate the albumin bound toxins that accumulate in liver failure.  
== History ==
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.
*There has been an increase in interest in the research on extra-corporeal liver support within past 5 decades.
*In the mid of 1990s, the [[liver]] dialysis was introduced.
*In 2005, the first MARS unit was established in the [[Toronto General Hospital]], Canada.
*In 2017, the new liver dialysis device DIALIVE was introduced.
*On 24 July 2017, the first patient to undergo liver dialysis with DIALIVE was recruited in London.
*The researchers are expecting to obtain the regulatory approval for DIALIVE by 2019 or 2020.


Hemodialysis is used for [[renal failure]] and primarily removes water soluble toxins, however it does not remove toxins bound to [[human serum albumin|albumin]] that accumulate in liver failure.
== Indications ==
Accepted indications for liver dialysis include the following:<ref name="pmid15667509">{{cite journal |vauthors=Sen S, Williams R, Jalan R |title=Emerging indications for albumin dialysis |journal=Am. J. Gastroenterol. |volume=100 |issue=2 |pages=468–75 |year=2005 |pmid=15667509 |doi=10.1111/j.1572-0241.2005.40864.x |url=}}</ref><ref name="DemetriouBrown2004">{{cite journal|last1=Demetriou|first1=Achilles A.|last2=Brown|first2=Robert S.|last3=Busuttil|first3=Ronald W.|last4=Fair|first4=Jeffrey|last5=McGuire|first5=Brendan M.|last6=Rosenthal|first6=Philip|last7=Am Esch|first7=Jan Schulte|last8=Lerut|first8=Jan|last9=Nyberg|first9=Scott L.|last10=Salizzoni|first10=Mauro|last11=Fagan|first11=Elizabeth A.|last12=de Hemptinne|first12=Bernard|last13=Broelsch|first13=Christoph E.|last14=Muraca|first14=Maurizio|last15=Salmeron|first15=Joan Manuel|last16=Rabkin|first16=John M.|last17=Metselaar|first17=Herold J.|last18=Pratt|first18=Daniel|last19=De La Mata|first19=Manuel|last20=McChesney|first20=Lawrence P.|last21=Everson|first21=Gregory T.|last22=Lavin|first22=Philip T.|last23=Stevens|first23=Anthony C.|last24=Pitkin|first24=Zorina|last25=Solomon|first25=Barry A.|title=Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure|journal=Annals of Surgery|volume=239|issue=5|year=2004|pages=660–670|issn=0003-4932|doi=10.1097/01.sla.0000124298.74199.e5}}</ref><ref name="pmid12682899">{{cite journal |vauthors=Doria C, Mandalá L, Smith J, Vitale CH, Lauro A, Gruttadauria S, Marino IR, Foglieni CS, Magnone M, Scott VL |title=Effect of molecular adsorbent recirculating system in hepatitis C virus-related intractable pruritus |journal=Liver Transpl. |volume=9 |issue=4 |pages=437–43 |year=2003 |pmid=12682899 |doi=10.1053/jlts.2003.50055 |url=}}</ref><ref name="pmid15878216">{{cite journal |vauthors=Sen S, Mookerjee RP, Cheshire LM, Davies NA, Williams R, Jalan R |title=Albumin dialysis reduces portal pressure acutely in patients with severe alcoholic hepatitis |journal=J. Hepatol. |volume=43 |issue=1 |pages=142–8 |year=2005 |pmid=15878216 |doi=10.1016/j.jhep.2005.01.032 |url=}}</ref><ref name="pmid12480556">{{cite journal |vauthors=Jalan R, Sen S, Steiner C, Kapoor D, Alisa A, Williams R |title=Extracorporeal liver support with molecular adsorbents recirculating system in patients with severe acute alcoholic hepatitis |journal=J. Hepatol. |volume=38 |issue=1 |pages=24–31 |year=2003 |pmid=12480556 |doi= |url=}}</ref><ref name="pmid12784049">{{cite journal |vauthors=Manz T, Ochs A, Bisse E, Strey C, Grotz W |title=Liver support--a task for nephrologists? Extracorporeal treatment of a patient with fulminant Wilson crisis |journal=Blood Purif. |volume=21 |issue=3 |pages=232–6 |year=2003 |pmid=12784049 |doi=10.1159/000070695 |url=}}</ref><ref name="pmid4128463">{{cite journal |vauthors=Mitskevich VM, Kotenko TV, Tsyganov VA, Shenin IuD |title=[Flavoviridomycin, a new tetraen antibiotic] |language=Russian |journal=Antibiotiki |volume=18 |issue=10 |pages=867–72 |year=1973 |pmid=4128463 |doi= |url=}}</ref><ref name="pmid12220303">{{cite journal |vauthors=Novelli G, Rossi M, Pretagostini R, Poli L, Novelli L, Berloco P, Ferretti G, Iappelli M, Cortesini R |title=MARS (Molecular Adsorbent Recirculating System): experience in 34 cases of acute liver failure |journal=Liver |volume=22 Suppl 2 |issue= |pages=43–7 |year=2002 |pmid=12220303 |doi= |url=}}</ref><ref name="pmid12619027">{{cite journal |vauthors=Schmidt LE, Wang LP, Hansen BA, Larsen FS |title=Systemic hemodynamic effects of treatment with the molecular adsorbents recirculating system in patients with hyperacute liver failure: a prospective controlled trial |journal=Liver Transpl. |volume=9 |issue=3 |pages=290–7 |year=2003 |pmid=12619027 |doi=10.1053/jlts.2003.50051 |url=}}</ref><ref name="pmid12220304">{{cite journal |vauthors=Chen S, Zhang L, Shi Y, Yang X, Wang M |title=Molecular Adsorbent Recirculating System: clinical experience in patients with liver failure based on hepatitis B in China |journal=Liver |volume=22 Suppl 2 |issue= |pages=48–51 |year=2002 |pmid=12220304 |doi= |url=}}</ref><ref name="pmid16023249">{{cite journal |vauthors=Krisper P, Haditsch B, Stauber R, Jung A, Stadlbauer V, Trauner M, Holzer H, Schneditz D |title=In vivo quantification of liver dialysis: comparison of albumin dialysis and fractionated plasma separation |journal=J. Hepatol. |volume=43 |issue=3 |pages=451–7 |year=2005 |pmid=16023249 |doi=10.1016/j.jhep.2005.02.038 |url=}}</ref><ref name="pmid14735236">{{cite journal |vauthors=Sen S, Ytrebø LM, Rose C, Fuskevaag OM, Davies NA, Nedredal GI, Williams R, Revhaug A, Jalan R |title=Albumin dialysis: a new therapeutic strategy for intoxication from protein-bound drugs |journal=Intensive Care Med |volume=30 |issue=3 |pages=496–501 |year=2004 |pmid=14735236 |doi=10.1007/s00134-003-2141-0 |url=}}</ref><ref name="pmid12969110">{{cite journal |vauthors=Koivusalo AM, Yildirim Y, Vakkuri A, Lindgren L, Höckerstedt K, Isoniemi H |title=Experience with albumin dialysis in five patients with severe overdoses of paracetamol |journal=Acta Anaesthesiol Scand |volume=47 |issue=9 |pages=1145–50 |year=2003 |pmid=12969110 |doi= |url=}}</ref><ref name="pmid15176968">{{cite journal |vauthors=Rubik J, Pietraszek-Jezierska E, Kamiński A, Skarzynska A, Jóźwiak S, Pawłowska J, Drewniak T, Prokurat S, Grenda R, Kaliciński P |title=Successful treatment of a child with fulminant liver failure and coma caused by Amanita phalloides intoxication with albumin dialysis without liver transplantation |journal=Pediatr Transplant |volume=8 |issue=3 |pages=295–300 |year=2004 |pmid=15176968 |doi=10.1111/j.1399-3046.2004.00170.x |url=}}</ref><ref name="pmid12950957">{{cite journal |vauthors=Covic A, Goldsmith DJ, Gusbeth-Tatomir P, Volovat C, Dimitriu AG, Cristogel F, Bizo A |title=Successful use of Molecular Absorbent Regenerating System (MARS) dialysis for the treatment of fulminant hepatic failure in children accidentally poisoned by toxic mushroom ingestion |journal=Liver Int. |volume=23 Suppl 3 |issue= |pages=21–7 |year=2003 |pmid=12950957 |doi= |url=}}</ref><ref name="pmid14531174">{{cite journal |vauthors=Faybik P, Hetz H, Krenn CG, Baker A, Germann P, Berlakovich G, Steininger R, Steltzer H |title=Liver support in fulminant liver failure after hemorrhagic shock |journal=Wien. Klin. Wochenschr. |volume=115 |issue=15-16 |pages=595–8 |year=2003 |pmid=14531174 |doi= |url=}}</ref><ref name="pmid15580335">{{cite journal |vauthors=Lahdenperä A, Koivusalo AM, Vakkuri A, Höckerstedt K, Isoniemi H |title=Value of albumin dialysis therapy in severe liver insufficiency |journal=Transpl. Int. |volume=17 |issue=11 |pages=717–23 |year=2005 |pmid=15580335 |doi=10.1007/s00147-004-0796-2 |url=}}</ref><ref name="pmid12234277">{{cite journal |vauthors=Hommann M, Kasakow LB, Geoghegan J, Kornberg A, Schotte U, Fuchs D, Hermann J, Zintl F, Scheele J |title=Application of MARS artificial liver support as bridging therapy before split liver retransplantation in a 15-month-old child |journal=Pediatr Transplant |volume=6 |issue=4 |pages=340–3 |year=2002 |pmid=12234277 |doi= |url=}}</ref><ref name="pmid12950961">{{cite journal |vauthors=van de Kerkhove MP, de Jong KP, Rijken AM, de Pont AC, van Gulik TM |title=MARS treatment in posthepatectomy liver failure |journal=Liver Int. |volume=23 Suppl 3 |issue= |pages=44–51 |year=2003 |pmid=12950961 |doi= |url=}}</ref><ref name="pmid15180733">{{cite journal |vauthors=Parés A, Cisneros L, Salmerón JM, Caballería L, Mas A, Torras A, Rodés J |title=Extracorporeal albumin dialysis: a procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis |journal=Am. J. Gastroenterol. |volume=99 |issue=6 |pages=1105–10 |year=2004 |pmid=15180733 |doi=10.1111/j.1572-0241.2004.30204.x |url=}}</ref><ref name="Majcher-PeszynskaPeszynski2001">{{cite journal|last1=Majcher-Peszynska|first1=J|last2=Peszynski|first2=P|last3=Müller|first3=S C|last4=Klammt|first4=S|last5=Wacke|first5=R|last6=Mitzner|first6=S|last7=Stange|first7=J|last8=Mundkowski|first8=R|last9=Hehl|first9=E-M|last10=Schmidt|first10=R|last11=Drewelow|first11=B|title=Drugs in liver disease and during albumin dialysis -MARS|journal=Zeitschrift für Gastroenterologie|volume=39|year=2001|pages=33–35|issn=0044-2771|doi=10.1055/s-2001-919048}}</ref>
*[[Acute liver failure]]
*Acute on [[chronic liver failure]]  
*Acute liver injury following [[Acetaminophen toxicity|paracetamol overdose]]
*Acutely decmpensated [[liver cirrhosis]]
*[[Budd-Chiari syndrome|Budd Chiari syndrome]]
*[[Endotoxins|Endotoxemia]]
*[[Fulminant hepatic failure]]
*Fulminant [[Wilson's disease|Wilson disease]]
*Sub fulminant [[hepatic failure]]
*[[Hepatic encephalopathy]] gade 2 or above
*[[Hyperbilirubinemia]] >5mg/dl
*[[Hepatorenal syndrome]]
*[[Hemochromatosis]]
*Increased [[Intracranial pressure|intracraneal pressure]]
*Progressive [[hyperbilirubinemia]]
*Progressive [[intrahepatic cholestasis]]
*[[Reye's syndrome|Reye syndrome]]
*[[Transcatheter arterial chemoembolization|Transarterial Chemoembolization]] (TACE)


== Liver dialysis prognosis/survival ==
== Contraindications ==
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 [[liver transplantation|transplantation]] or liver regeneration (in the case of [[acute liver failure]])<ref>O'grady J. Personal view: current role of artificial liver support devices. Aliment Pharmacol Ther. 2006 Jun 1;23(11):1549-57. PMID 16696802.</ref><ref>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. [http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=15273544 Free Full Text].</ref><ref>Neuberger J. Prediction of survival for patients with fulminant hepatic failure. Hepatology. 2005 Jan;41(1):19-22. PMID 15690476.</ref> and, unlike [[kidney dialysis]] (for [[renal failure]]), cannot support a patient for an extended period of time (months to years).
Contraindications for Liver dialysis include the following:
*Unstable hemodynamics with mean arterial pressure (MAP) <55 mmHg despite the use of [[vasoconstrictors]]
*[[Thrombocytopenia]], [[Platelet|platelets]] count < 50,000
*[[Disseminated intravascular coagulation]] (DIC)  
*[[INR]] over 2.3
*Uncontrolled [[infection]]
*Uncontrolled [[hemorrhage]]
*Intrinsic [[renal disease]]
*Candidate for [[Renal replacement therapy|renal replacement therapy]]
*[[Polycystic liver disease|Polycystic liver disease]]
*Severe [[Right heart failure|right-heart failure]]


== Liver dialysis devices ==
== 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.
Artificial [[detoxification]] liver dialysis devices currently under clinical evaluation include:
*Molecular Adsorbent Recirculating System (MARS)
*Single Pass Albumin Dialysis (SPAD)
*Prometheus system
*DIALIVE


=== Molecular Adsorbents Recirculation System (MARS) ===<!-- This section is linked from [[Mars (disambiguation)]] -->
=== 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 '''Molecular Adsorbents Recirculation System (MARS) ,''' its development was started at the University of Rostock in Germany and later was developed by Teraklin AG of Germany.
The MARS system can remove a number of toxins, including [[ammonia]], [[bile acids]], [[bilirubin]], [[copper]], [[iron]] and [[phenols]].
*MARS is the best available extracorporeal liver dialysis device till date.
 
*The MARS is in use for liver dialysis for approximately ten years.
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.[http://www.gambro.com/upload/Press%20Releases/2005/MARS_510k.pdf]  Canada's first MARS unit arrived at the [[Toronto General Hospital]] in 2005.
*The two separate dialysis circuits for MARS include:
{|
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Circuit
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Components
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Mechanism
|-
! style="background:#DCDCDC;" align="center" + |Circuit 1
| style="background:#F5F5F5;" |[[Human serum albumin]]
| style="background:#F5F5F5;" |Circuit one is connected to the patient's [[blood]] through a [[semipermeable membrane]] which contains two special filters that cleanse the [[albumin]] after it absorbs toxins from the patient's blood such as [[ammonia]], [[aromatic amino acids]], [[mercaptans]], [[bilirubin]], [[Bile acid|bile acids,]] [[Cytokine|cytokines]], [[Tryptophan|tryptophans]] and [[nitric oxide]].
|-
! style="background:#DCDCDC;" align="center" + |Circuit 2
| style="background:#F5F5F5;" |[[Hemodialysis]] machine
| style="background:#F5F5F5;" |Circuit two cleanses the [[albumin]] from the first circuit before its re-circulation though the [[semipermeable membrane]] before it comes in contact with the patient's [[blood]].
|}


=== Single Pass Albumin Dialysis (SPAD) ===
=== Single Pass Albumin Dialysis (SPAD) ===
'''Single pass albumin dialysis (SPAD)''' is a simple method of [[human serum albumin|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.  
*SPAD is a simple method of [[human serum albumin|albumin]] dialysis
'''Mechanism'''
*It operates using standard [[renal replacement therapy]] machines without any additional perfusion pump system.
*The patient’s blood passses through the circuit with a high flux hollow fiber hemodiafilter which is identical to the one used in the MARS system.
*The auxillary side of the membrane is cleansed with an albumin solution in counter-directional flow, which is junked away after going through filtration.
*[[Hemodialysis]] can be also be performed during the first circuit using the same high-flux hollow fibers.


=== Comparing SPAD, MARS and CVVHDF ===
=== Comparing MARS, SPAD, and Veno-venous haemodiafiltratio (CVVHDF) ===
SPAD, MARS and continuous veno-venous haemodiafiltration (CVVHDF) were compared [[in vitro]] with regard to detoxification capacity.<ref>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.</ref> 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.
*In 2004, an [[in vitro]] comparison study was published regarding detoxification capacity of MARS, SPAD and continuous veno-venous haemodiafiltration (CVVHDF).<ref name="pmid15122770">{{cite journal |vauthors=Sauer IM, Goetz M, Steffen I, Walter G, Kehr DC, Schwartlander R, Hwang YJ, Pascher A, Gerlach JC, Neuhaus P |title=In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD) |journal=Hepatology |volume=39 |issue=5 |pages=1408–14 |year=2004 |pmid=15122770 |doi=10.1002/hep.20195 |url=}}</ref>
{|
! colspan="6" style="background:#4479BA; color: #FFFFFF;" align="center" + |Comparison between MARS, SPAD and CVVHDF
|-
! rowspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Device
! colspan="4" style="background:#4479BA; color: #FFFFFF;" align="center" + |Detoxification capacity
! rowspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Cost effectivenss
|-
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Ammonia
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Bilirubin
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Bile acids
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Water soluble substances
|-
| style="background:#F5F5F5;" align="center" + |MARS
| style="background:#F5F5F5;+ " |Significantly lower reduction
| style="background:#F5F5F5;+ " |Significantly lower reduction
| style="background:#F5F5F5;+ " |No significant differences
| style="background:#F5F5F5;+ " |No significant differences
| style="background:#F5F5F5;+ " |More Expensive (approximately € 2165)
|-
| style="background:#F5F5F5;" align="center" + |SPAD
| style="background:#F5F5F5;+ " |Significantly greater reduction
| style="background:#F5F5F5;+ " |Significantly greater reduction
| style="background:#F5F5F5;+ " |No significant differences
| style="background:#F5F5F5;+ " |No significant differences
| style="background:#F5F5F5;+ " |Less Expansive (approximately € 656)
|-
| style="background:#F5F5F5;" align="center" + |CVVHDF
| style="background:#F5F5F5;+ " |Significantly greater reduction
| style="background:#F5F5F5;+ " |Significantly lower reduction
| style="background:#F5F5F5;+ " |No significant differences
| style="background:#F5F5F5;+ " |No significant differences
| style="background:#F5F5F5;+ " |Cheap
|}


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.
=== Prometheus ===
*The prometheus system is a device invented recently by Fresenius Medical Care of Bad Homburg, Germany.<ref name="pmid14642616">{{cite journal |vauthors=Rifai K, Ernst T, Kretschmer U, Bahr MJ, Schneider A, Hafer C, Haller H, Manns MP, Fliser D |title=Prometheus--a new extracorporeal system for the treatment of liver failure |journal=J. Hepatol. |volume=39 |issue=6 |pages=984–90 |year=2003 |pmid=14642616 |doi= |url=}}</ref>
*It is composed of the unification of [[human serum albumin|albumin]] [[adsorption]] with high-flux [[hemodialysis]] after precise filtration of the [[albumin]] fraction through a peculiar polysulfon filter called as the '''Albuflow'''.
*This  study was conducted among a group of eleven patients who were suffering from [[hepatorenal syndrome]], acute on chronic [[Hepatic failure|liver failure]], and accompanying renal failure.
*Over four hours sessions for two succesive days demonstrated improved [[serum]] levels of [[ammonia]], [[Bile acid|bile acids]], [[conjugated bilirubin]], [[cholinesterase]], [[creatinine]], [[urea]], and [[PH|blood pH]].  
*Prometheus has proven to be a safe supportive management for the patients with [[Hepatic failure|liver failure]].<ref name="RifaiErnst2003">{{cite journal|last1=Rifai|first1=Kinan|last2=Ernst|first2=Thomas|last3=Kretschmer|first3=Ulrich|last4=Bahr|first4=Matthias J|last5=Schneider|first5=Andrea|last6=Hafer|first6=Carsten|last7=Haller|first7=Hermann|last8=Manns|first8=Michael P|last9=Fliser|first9=Danilo|title=Prometheus® – a new extracorporeal system for the treatment of liver failure☆|journal=Journal of Hepatology|volume=39|issue=6|year=2003|pages=984–990|issn=01688278|doi=10.1016/S0168-8278(03)00468-9}}</ref>


=== Prometheus ===
=== DIALIVE===
The '''Prometheus''' system ([[Fresenius AG|Fresenius]] Medical Care, [[Bad Homburg]], [[Germany]]) is a new device based on the combination of [[human serum albumin|albumin]] [[adsorption]] with high-flux [[hemodialysis]] after selective filtration of the albumin fraction through a specific polysulfon filter (AlbuFlow). It has been studied<ref>Rifai K, Ernst T, Kretschmer U, Bahr MJ, Schneider A, Hafer C, Haller H, Manns MP, Fliser D. Prometheus--a new extracorporeal system for the treatment of liver failure. J Hepatol. 2003 Dec;39(6):984-90. PMID 14642616.</ref> 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.
* The new liver dialysis device DIALIVE was introduced in 2017.<ref name="urlNew Liver Dialysis Device to Be Tested in Europe - Hep">{{cite web |url=https://www.hepmag.com/article/new-liver-dialysis-device-tested-europe |title=New Liver Dialysis Device to Be Tested in Europe - Hep |format= |work= |accessdate=}}</ref>
* Dialive is a new emerging system that consolidates [[albumin]] removal, replacement, and [[endotoxin]] removal.
* The researchers are expecting to obtain the regulatory approval for DIALIVE in 2019 or 2020.
* Among the animal models of [[liver failure]] it revealed that it is:<ref name="urlSafety and Performance Trial of DIALIVE Liver Dialysis Device in Acute On Chronic Liver Failure Patients - Full Text View - ClinicalTrials.gov">{{cite web |url=https://clinicaltrials.gov/ct2/show/NCT03065699?term=YAQRIT&rank=1 |title=Safety and Performance Trial of DIALIVE Liver Dialysis Device in Acute On Chronic Liver Failure Patients - Full Text View - ClinicalTrials.gov |format= |work= |accessdate=}}</ref>
** Safe and easy to use
** Reduce [[Endotoxins|endotoxemia]]
** Improve [[albumin]]
** Improve [[immune]] function
** Prolong survival


==References==
== Liver dialysis prognosis ==
<references/>
*At present liver dialysis is only thought to be a bridge for [[liver transplantation]] or liver regeneration.<ref name="pmid16696802">{{cite journal |vauthors=O'Grady J |title=Personal view: current role of artificial liver support devices |journal=Aliment. Pharmacol. Ther. |volume=23 |issue=11 |pages=1549–57 |year=2006 |pmid=16696802 |doi=10.1111/j.1365-2036.2006.02931.x |url=}}</ref><ref name="pmid15273544">{{cite journal |vauthors=van de Kerkhove MP, Hoekstra R, Chamuleau RA, van Gulik TM |title=Clinical application of bioartificial liver support systems |journal=Ann. Surg. |volume=240 |issue=2 |pages=216–30 |year=2004 |pmid=15273544 |pmc=1356396 |doi= |url=}}</ref><ref name="pmid15690476">{{cite journal |vauthors=Neuberger J |title=Prediction of survival for patients with fulminant hepatic failure |journal=Hepatology |volume=41 |issue=1 |pages=19–22 |year=2005 |pmid=15690476 |doi=10.1002/hep.20562 |url=}}</ref>.
*Liver dialysis is a new techinque and the prognosis of patients with [[liver failure]] is still guarded.
*The survival rate with liver dialysis is up to thirty days.
*Liver dialysis cannot support a patient for a longer period of time like [[renal dialysis]].


== Complications ==
The complications of liver dialysis are:
*[[Hemorrhage]]
*Secondary [[Infection|infections]]
*[[Hypotension]]
==Related Chapters==
==Related Chapters==
*[[American Society for Artificial Internal Organs]] and [http://www.esao.org/ European Society for Artificial Organs]
*[[American Society for Artificial Internal Organs]] and [http://www.esao.org/ European Society for Artificial Organs]
Line 51: Line 153:
*[[Bioartificial liver device]]
*[[Bioartificial liver device]]


==External Links==
==Reference==
* Sen S, Williams R, Jalan R. Emerging indications for albumin dialysis. Am J Gastroenterol. 2005 Feb;100(2):468-75. Review. PMID 15667509
{{Reflist|2}}
* [http://lab.blogs.com/lswg/ Liver Support Working Group of the European Society for Artficial Organs (ESA0)]
​​
===MARS===
​
* [http://gambro.com/Pages/InfoPage.aspx?id=9068 Gambro] - the manufacturer of the MARS.
* [http://biomed.brown.edu/Courses/BI108/BI108_2002_Groups/liver/webpage/MARSpg.htm MARS - Molecular Adsorbent Recycling System (Teraklin)] - a description of the MARS.
* [http://www.chirurgieinfo.com/de/mars.html 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
===SPAD===
* [http://www.charite.de/avt/research/sauer/projects/mels_lab/detox_module/detox_start.html Artificial Liver Support Systems] - [http://www.charite.de/avt/research/sauer/ 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
* [http://www.charite.de/avt/research/sauer/projects/mels_lab/mels_start.html Modular Extracorporeal Liver Support (MELS)] - [http://www.charite.de/avt/research/sauer/ Charité Berlin - Campus Virchow - Division of Experimental Surgery and Regenerative Medicine]
===Prometheus===
* [http://www.equl.com/products/info/bio_liver/prometheus.htm The Prometheus System] - a description from equl.com
* [http://www.donau-uni.ac.at/en/studium/fachabteilungen/umwelt/zentren/biomed/projekte/archiv/01241/index.php  The Prometheus System - Development of an Adsorptive Blood Purification System called Prometheus] - Donau-Universität Krems
 
{{Digestive system surgical procedures}}
{{Digestive system surgical procedures}}
[[de:Leberdialyse]]


[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Up-To-Date]]
[[Category:Hepatology]]
[[Category:Hepatology]]
[[de:Leberdialyse]]

Latest revision as of 22:31, 29 July 2020

Liver dialysis Microchapters

Overview

History

Indications

Contraindications

Liver Dialysis Devices

•Molecular Adsorbents Recirculation System (MARS)
•Single Pass Albumin Dialysis (SPAD)
•Comparing MARS, SPAD, and Veno-venous haemodiafiltratio(CVVHDF)
•Prometheus
•DIALIVE

Liver dialysis prognosis

Complications

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]

This article specifically discusses liver dialysis. For information regarding kidney dialysis or dialysis in general, please click here.

Overview

Liver dialysis is a type of artificial extracorporeal liver support. It is a new promising emerging therapeutic technique used for the detoxification treatment for liver failure and it has shown positive impact on the outcomes of hepatorenal syndrome. Liver dialysis follows the same principles of hemodialysis. The concerning matter during a liver failure is the accumulation of toxins in the blood stream which are not cleared by an injured liver. Based on this hypothesis, the elimination of albumin-bound substances such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty acids and cytokines has led to the invention of artificial filtration and adsorption devices. Several new devices are invented for this purpose such as Molecular Adsorbent Recirculating System (MARS), Single Pass Albumin Dialysis (SPAD), Prometheus system and DIALIVE. Hemodialysis is used for renal failure which mainly eliminates water soluble toxins, but it can not eliminate the albumin bound toxins that accumulate in liver failure.

History

  • There has been an increase in interest in the research on extra-corporeal liver support within past 5 decades.
  • In the mid of 1990s, the liver dialysis was introduced.
  • In 2005, the first MARS unit was established in the Toronto General Hospital, Canada.
  • In 2017, the new liver dialysis device DIALIVE was introduced.
  • On 24 July 2017, the first patient to undergo liver dialysis with DIALIVE was recruited in London.
  • The researchers are expecting to obtain the regulatory approval for DIALIVE by 2019 or 2020.

Indications

Accepted indications for liver dialysis include the following:[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]

Contraindications

Contraindications for Liver dialysis include the following:

Liver Dialysis Devices

Artificial detoxification liver dialysis devices currently under clinical evaluation include:

  • Molecular Adsorbent Recirculating System (MARS)
  • Single Pass Albumin Dialysis (SPAD)
  • Prometheus system
  • DIALIVE

Molecular Adsorbents Recirculation System (MARS)

  • The Molecular Adsorbents Recirculation System (MARS) , its development was started at the University of Rostock in Germany and later was developed by Teraklin AG of Germany.
  • MARS is the best available extracorporeal liver dialysis device till date.
  • The MARS is in use for liver dialysis for approximately ten years.
  • The two separate dialysis circuits for MARS include:
Circuit Components Mechanism
Circuit 1 Human serum albumin Circuit one is connected to the patient's blood through a semipermeable membrane which contains two special filters that cleanse the albumin after it absorbs toxins from the patient's blood such as ammonia, aromatic amino acids, mercaptans, bilirubin, bile acids, cytokines, tryptophans and nitric oxide.
Circuit 2 Hemodialysis machine Circuit two cleanses the albumin from the first circuit before its re-circulation though the semipermeable membrane before it comes in contact with the patient's blood.

Single Pass Albumin Dialysis (SPAD)

  • SPAD is a simple method of albumin dialysis

Mechanism

  • It operates using standard renal replacement therapy machines without any additional perfusion pump system.
  • The patient’s blood passses through the circuit with a high flux hollow fiber hemodiafilter which is identical to the one used in the MARS system.
  • The auxillary side of the membrane is cleansed with an albumin solution in counter-directional flow, which is junked away after going through filtration.
  • Hemodialysis can be also be performed during the first circuit using the same high-flux hollow fibers.

Comparing MARS, SPAD, and Veno-venous haemodiafiltratio (CVVHDF)

  • In 2004, an in vitro comparison study was published regarding detoxification capacity of MARS, SPAD and continuous veno-venous haemodiafiltration (CVVHDF).[22]
Comparison between MARS, SPAD and CVVHDF
Device Detoxification capacity Cost effectivenss
Ammonia Bilirubin Bile acids Water soluble substances
MARS Significantly lower reduction Significantly lower reduction No significant differences No significant differences More Expensive (approximately € 2165)
SPAD Significantly greater reduction Significantly greater reduction No significant differences No significant differences Less Expansive (approximately € 656)
CVVHDF Significantly greater reduction Significantly lower reduction No significant differences No significant differences Cheap

Prometheus

DIALIVE

  • The new liver dialysis device DIALIVE was introduced in 2017.[25]
  • Dialive is a new emerging system that consolidates albumin removal, replacement, and endotoxin removal.
  • The researchers are expecting to obtain the regulatory approval for DIALIVE in 2019 or 2020.
  • Among the animal models of liver failure it revealed that it is:[26]

Liver dialysis prognosis

  • At present liver dialysis is only thought to be a bridge for liver transplantation or liver regeneration.[27][28][29].
  • Liver dialysis is a new techinque and the prognosis of patients with liver failure is still guarded.
  • The survival rate with liver dialysis is up to thirty days.
  • Liver dialysis cannot support a patient for a longer period of time like renal dialysis.

Complications

The complications of liver dialysis are:

Related Chapters

Reference

  1. ↑ Sen S, Williams R, Jalan R (2005). "Emerging indications for albumin dialysis". Am. J. Gastroenterol. 100 (2): 468–75. doi:10.1111/j.1572-0241.2005.40864.x. PMID 15667509.
  2. ↑ Demetriou, Achilles A.; Brown, Robert S.; Busuttil, Ronald W.; Fair, Jeffrey; McGuire, Brendan M.; Rosenthal, Philip; Am Esch, Jan Schulte; Lerut, Jan; Nyberg, Scott L.; Salizzoni, Mauro; Fagan, Elizabeth A.; de Hemptinne, Bernard; Broelsch, Christoph E.; Muraca, Maurizio; Salmeron, Joan Manuel; Rabkin, John M.; Metselaar, Herold J.; Pratt, Daniel; De La Mata, Manuel; McChesney, Lawrence P.; Everson, Gregory T.; Lavin, Philip T.; Stevens, Anthony C.; Pitkin, Zorina; Solomon, Barry A. (2004). "Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure". Annals of Surgery. 239 (5): 660–670. doi:10.1097/01.sla.0000124298.74199.e5. ISSN 0003-4932.
  3. ↑ Doria C, Mandalá L, Smith J, Vitale CH, Lauro A, Gruttadauria S, Marino IR, Foglieni CS, Magnone M, Scott VL (2003). "Effect of molecular adsorbent recirculating system in hepatitis C virus-related intractable pruritus". Liver Transpl. 9 (4): 437–43. doi:10.1053/jlts.2003.50055. PMID 12682899.
  4. ↑ Sen S, Mookerjee RP, Cheshire LM, Davies NA, Williams R, Jalan R (2005). "Albumin dialysis reduces portal pressure acutely in patients with severe alcoholic hepatitis". J. Hepatol. 43 (1): 142–8. doi:10.1016/j.jhep.2005.01.032. PMID 15878216.
  5. ↑ Jalan R, Sen S, Steiner C, Kapoor D, Alisa A, Williams R (2003). "Extracorporeal liver support with molecular adsorbents recirculating system in patients with severe acute alcoholic hepatitis". J. Hepatol. 38 (1): 24–31. PMID 12480556.
  6. ↑ Manz T, Ochs A, Bisse E, Strey C, Grotz W (2003). "Liver support--a task for nephrologists? Extracorporeal treatment of a patient with fulminant Wilson crisis". Blood Purif. 21 (3): 232–6. doi:10.1159/000070695. PMID 12784049.
  7. ↑ Mitskevich VM, Kotenko TV, Tsyganov VA, Shenin I (1973). "[Flavoviridomycin, a new tetraen antibiotic]". Antibiotiki (in Russian). 18 (10): 867–72. PMID 4128463. Vancouver style error: initials (help)
  8. ↑ Novelli G, Rossi M, Pretagostini R, Poli L, Novelli L, Berloco P, Ferretti G, Iappelli M, Cortesini R (2002). "MARS (Molecular Adsorbent Recirculating System): experience in 34 cases of acute liver failure". Liver. 22 Suppl 2: 43–7. PMID 12220303.
  9. ↑ Schmidt LE, Wang LP, Hansen BA, Larsen FS (2003). "Systemic hemodynamic effects of treatment with the molecular adsorbents recirculating system in patients with hyperacute liver failure: a prospective controlled trial". Liver Transpl. 9 (3): 290–7. doi:10.1053/jlts.2003.50051. PMID 12619027.
  10. ↑ Chen S, Zhang L, Shi Y, Yang X, Wang M (2002). "Molecular Adsorbent Recirculating System: clinical experience in patients with liver failure based on hepatitis B in China". Liver. 22 Suppl 2: 48–51. PMID 12220304.
  11. ↑ Krisper P, Haditsch B, Stauber R, Jung A, Stadlbauer V, Trauner M, Holzer H, Schneditz D (2005). "In vivo quantification of liver dialysis: comparison of albumin dialysis and fractionated plasma separation". J. Hepatol. 43 (3): 451–7. doi:10.1016/j.jhep.2005.02.038. PMID 16023249.
  12. ↑ Sen S, Ytrebø LM, Rose C, Fuskevaag OM, Davies NA, Nedredal GI, Williams R, Revhaug A, Jalan R (2004). "Albumin dialysis: a new therapeutic strategy for intoxication from protein-bound drugs". Intensive Care Med. 30 (3): 496–501. doi:10.1007/s00134-003-2141-0. PMID 14735236.
  13. ↑ Koivusalo AM, Yildirim Y, Vakkuri A, Lindgren L, Höckerstedt K, Isoniemi H (2003). "Experience with albumin dialysis in five patients with severe overdoses of paracetamol". Acta Anaesthesiol Scand. 47 (9): 1145–50. PMID 12969110.
  14. ↑ Rubik J, Pietraszek-Jezierska E, Kamiński A, Skarzynska A, Jóźwiak S, Pawłowska J, Drewniak T, Prokurat S, Grenda R, Kaliciński P (2004). "Successful treatment of a child with fulminant liver failure and coma caused by Amanita phalloides intoxication with albumin dialysis without liver transplantation". Pediatr Transplant. 8 (3): 295–300. doi:10.1111/j.1399-3046.2004.00170.x. PMID 15176968.
  15. ↑ Covic A, Goldsmith DJ, Gusbeth-Tatomir P, Volovat C, Dimitriu AG, Cristogel F, Bizo A (2003). "Successful use of Molecular Absorbent Regenerating System (MARS) dialysis for the treatment of fulminant hepatic failure in children accidentally poisoned by toxic mushroom ingestion". Liver Int. 23 Suppl 3: 21–7. PMID 12950957.
  16. ↑ Faybik P, Hetz H, Krenn CG, Baker A, Germann P, Berlakovich G, Steininger R, Steltzer H (2003). "Liver support in fulminant liver failure after hemorrhagic shock". Wien. Klin. Wochenschr. 115 (15–16): 595–8. PMID 14531174.
  17. ↑ Lahdenperä A, Koivusalo AM, Vakkuri A, Höckerstedt K, Isoniemi H (2005). "Value of albumin dialysis therapy in severe liver insufficiency". Transpl. Int. 17 (11): 717–23. doi:10.1007/s00147-004-0796-2. PMID 15580335.
  18. ↑ Hommann M, Kasakow LB, Geoghegan J, Kornberg A, Schotte U, Fuchs D, Hermann J, Zintl F, Scheele J (2002). "Application of MARS artificial liver support as bridging therapy before split liver retransplantation in a 15-month-old child". Pediatr Transplant. 6 (4): 340–3. PMID 12234277.
  19. ↑ van de Kerkhove MP, de Jong KP, Rijken AM, de Pont AC, van Gulik TM (2003). "MARS treatment in posthepatectomy liver failure". Liver Int. 23 Suppl 3: 44–51. PMID 12950961.
  20. ↑ Parés A, Cisneros L, Salmerón JM, Caballería L, Mas A, Torras A, Rodés J (2004). "Extracorporeal albumin dialysis: a procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis". Am. J. Gastroenterol. 99 (6): 1105–10. doi:10.1111/j.1572-0241.2004.30204.x. PMID 15180733.
  21. ↑ Majcher-Peszynska, J; Peszynski, P; Müller, S C; Klammt, S; Wacke, R; Mitzner, S; Stange, J; Mundkowski, R; Hehl, E-M; Schmidt, R; Drewelow, B (2001). "Drugs in liver disease and during albumin dialysis -MARS". Zeitschrift für Gastroenterologie. 39: 33–35. doi:10.1055/s-2001-919048. ISSN 0044-2771.
  22. ↑ Sauer IM, Goetz M, Steffen I, Walter G, Kehr DC, Schwartlander R, Hwang YJ, Pascher A, Gerlach JC, Neuhaus P (2004). "In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD)". Hepatology. 39 (5): 1408–14. doi:10.1002/hep.20195. PMID 15122770.
  23. ↑ Rifai K, Ernst T, Kretschmer U, Bahr MJ, Schneider A, Hafer C, Haller H, Manns MP, Fliser D (2003). "Prometheus--a new extracorporeal system for the treatment of liver failure". J. Hepatol. 39 (6): 984–90. PMID 14642616.
  24. ↑ Rifai, Kinan; Ernst, Thomas; Kretschmer, Ulrich; Bahr, Matthias J; Schneider, Andrea; Hafer, Carsten; Haller, Hermann; Manns, Michael P; Fliser, Danilo (2003). "Prometheus® – a new extracorporeal system for the treatment of liver failure☆". Journal of Hepatology. 39 (6): 984–990. doi:10.1016/S0168-8278(03)00468-9. ISSN 0168-8278.
  25. ↑ "New Liver Dialysis Device to Be Tested in Europe - Hep".
  26. ↑ "Safety and Performance Trial of DIALIVE Liver Dialysis Device in Acute On Chronic Liver Failure Patients - Full Text View - ClinicalTrials.gov".
  27. ↑ O'Grady J (2006). "Personal view: current role of artificial liver support devices". Aliment. Pharmacol. Ther. 23 (11): 1549–57. doi:10.1111/j.1365-2036.2006.02931.x. PMID 16696802.
  28. ↑ van de Kerkhove MP, Hoekstra R, Chamuleau RA, van Gulik TM (2004). "Clinical application of bioartificial liver support systems". Ann. Surg. 240 (2): 216–30. PMC 1356396. PMID 15273544.
  29. ↑ Neuberger J (2005). "Prediction of survival for patients with fulminant hepatic failure". Hepatology. 41 (1): 19–22. doi:10.1002/hep.20562. PMID 15690476.

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