Liver dialysis Microchapters
Editor-In-Chief: C. Michael Gibson, M.S., M.D. ; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS 
This article specifically discusses liver dialysis. For information regarding kidney dialysis or dialysis in general, please click here.
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.
- 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.
Accepted indications for liver dialysis include the following:
- Acute liver failure
- Acute on chronic liver failure
- Acute liver injury following paracetamol overdose
- Acutely decmpensated liver cirrhosis
- Budd Chiari syndrome
- Fulminant hepatic failure
- Fulminant Wilson disease
- Sub fulminant hepatic failure
- Hepatic encephalopathy gade 2 or above
- Hyperbilirubinemia >5mg/dl
- Hepatorenal syndrome
- Increased intracraneal pressure
- Progressive hyperbilirubinemia
- Progressive intrahepatic cholestasis
- Reye syndrome
- Transarterial Chemoembolization (TACE)
Contraindications for Liver dialysis include the following:
- Unstable hemodynamics with mean arterial pressure (MAP) <55 mmHg despite the use of vasoconstrictors
- Thrombocytopenia, platelets count < 50,000
- Disseminated intravascular coagulation (DIC)
- INR over 2.3
- Uncontrolled infection
- Uncontrolled hemorrhage
- Intrinsic renal disease
- Candidate for renal replacement therapy
- Polycystic liver disease
- Severe right-heart failure
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
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 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
- 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).
|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|
- The prometheus system is a device invented recently by Fresenius Medical Care of Bad Homburg, Germany.
- It is composed of the unification of 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 liver failure, and accompanying renal failure.
- Over four hours sessions for two succesive days demonstrated improved serum levels of ammonia, bile acids, conjugated bilirubin, cholinesterase, creatinine, urea, and blood pH.
- Prometheus has proven to be a safe supportive management for the patients with liver failure.
- The new liver dialysis device DIALIVE was introduced in 2017.
- 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:
- Safe and easy to use
- Reduce endotoxemia
- Improve albumin
- Improve immune function
- Prolong survival
Liver dialysis prognosis
- At present liver dialysis is only thought to be a bridge for liver transplantation or liver regeneration..
- 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.
The complications of liver dialysis are:
- Secondary infections
- 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 (2005). "Emerging indications for albumin dialysis". Am. J. Gastroenterol. 100 (2): 468–75. doi:10.1111/j.1572-0241.2005.40864.x. PMID 15667509.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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)
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ "New Liver Dialysis Device to Be Tested in Europe - Hep".
- ↑ "Safety and Performance Trial of DIALIVE Liver Dialysis Device in Acute On Chronic Liver Failure Patients - Full Text View - ClinicalTrials.gov".
- ↑ 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.
- ↑ 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.
- ↑ 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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