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liver support systems

liver support systems

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Published by: drhananfathy on Feb 15, 2010
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10/09/2015

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Hanan Fathy

Liver failure - endogenous intoxication
Ongoing Imbalance of water-soluble and non-soluble substances
• Brain Function • Kidney Function • Cardiovascular Tone • Bone Marrow Activity

Toxins:
• Bile acids • Bilirubin • Prostacyclins • Nitric oxide Further liver damage • Indol / Phenol- via vicious cycle: • Metabolites necrosis/apoptosis !!! • Toxic fatty acids • Thiols • Digoxin/Diazepamlike subs. • ... • Ammonia • Lactate

Main Indication groups for liver support systems
1-Acute liver failure 2-Acute decompensation on chronic liver disease
– Complicated by progressive jaundice – Complicated by hepatic encephalopathy – Complicated by renal dysfunction

3-Intractable pruritus in cholestasis 4-Acute intoxication or overdose with substances potentially bound to albumin 5-Other indications
 Acute hepatic failure after major hepatectomy  After liver transplantation  Primary non-function or primary dysfunction of the graft  Acute decompensation of the graft  Secondary liver failure or multi-organ failure

Aim
• Bridge to liver transplantation • Bridge to allow sufficient time for hepatic regeneration • Improve clinical stability of patient

Toxin removal
Water based human body

water-soluble toxins
(free) Diffusion

non water-soluble toxins
(protein bound) Binding site related distribution

Filtration (unselective)

Dialysis Balance of water-soluble substances

Albumin Dialysis Balance of protein bound substances

Plasma exchange (unselective)

Liver support therapy

Liver support systems can be divided into two

main groups:

Non biologic liver support. Biologic liver support.

Biologic liver support

Millis JM and Losanoff JE (2005) Technology Insight: liver support systems Nat Clin Pract Gastroenterol Hepatol 2: 398–405 doi:10.1038/ncpgasthep0254

Nonbiologic liver support

Millis JM and Losanoff JE (2005) Technology Insight: liver support systems Nat Clin Pract Gastroenterol Hepatol 2: 398–405 doi:10.1038/ncpgasthep0254

Liver Support Systems

Molecular Adsorbent Recycling System (MARS)
 Removal of soluble and protein-bound substances against albumin-rich dialysate.

Fractionated plasma separation and adsorption (Prometheus).
 Fractionation of plasma and detoxification of albumin by adsorption.

Single-pass albumin dialysis.
 One-pass dialysis against albumin solution.

Non-Biological Filtration Techniques
• Molecular Adsorbents Recycling System (MARS)
– Commercially available-premise based on filtering out albumin bound toxins – Uses albumin-enriched dialysate combined with a charcoal filter and an ion exchange resin – Utilizes existing Renal Dialysis Machinery along with the MARS device

Non-Biological Filtration Techniques
• Albumin dialysis pumps the blood out of the body and into a plastic tube filled with hollow fibers made of a membrane that has been coated with albumin. • On one side of the fiber's membrane is the blood; on the other, a dialysis solution containing more albumin.

Non-Biological Filtration Techniques
• The toxins on the albumin in the patient's blood are attracted to the albumin on the membrane, which is "stickier" because it has more room for molecules to attach. • Then, the albumin on the membrane passes the toxins along to the albumin in the solution as it flows by.

Non-Biological Filtration Techniques
• Meanwhile, smaller toxin molecules that don't stick to albumin flow through the membrane's tiny pores into the lessconcentrated dialysis solution. • The patient's own albumin, too large to fit through the membrane's pores, returns to the body with the blood.

MARS
Albumin 20% 600ml

Low-flux D

High-flux D High-flux High-flux D D

Patient

Filtrate recirculation circuit

MARS

The MARS principle
®

The MARS membrane
®

®

MARS Absorber cartridges
®

• Activated charcoal column
(diaMARS® AC250)

• Anion-exchanger resin column

Liver support therapy

Among the toxins that MARS can remove are:
 Short and middle chain fatty Bile acids acids Bilirubin  Benzodiazepine like substances Aromatic aminoacids  Nitric oxide  Ammonia Phenols  Creatinine Mercaptans  Urea Dioxin –like substances  Copper  Iron

Tryptophan

Prometheus Circuit

Prometh 01 column contains highly porous neutral resin for the removal of albumin bound toxins such as bile acids, aromatic Acids & phenolic substances. The Inner part is highly porous & offers a huge surface area with multiple binding sites to toxins Prometh 02 column contains anion exchange resins with spongy inner portions to increase surface area. It contains positively charged ligands capable of binding negatively charged substances ex: unconjugated bilirubin

Hemodialysis and liver dialysis (2 systems in 1)
20

Liver Support Therapy: Prometheus Machines Prometheus: Hemodialysis & Liver Dialysis

Prometheus Citrate

Prometheus Heparin

21

Toxin Elimination
The Liver‘s Poison Cabinet
Toxins Damage Hepat. Encephalopathy Kidney failure (HRS) Hepat. Encephalopathy Hepat. Encephalopathy Hepat. Encephalopathy Pruritus Hemodyn. Instability Hepat. Encephalopathy Elimination Dialysis Dialysis Dialysis/02 prometh01 prometh01 prometh01 prometh 01 prometh01

water soluble

Ammonia Creatinin, urea Bilirubin Benzodiazepine Arom. amino acids Bile acids Nitrogen oxide Indols, phenols

albumin bound

• In-vivo comparisons of both systems showed : • significantly higher extraction capacities for protein-bound and water-soluble substances under Prometheus than under MARS treatment.

Continuous Veno- Venous Single Pass Albumin Haemodiafiltration ( SPAD)
Roler pump 1
Substitute 330ml/h

Roler pump 2
Albumin 20% . 70 ml/h

Substitute pump
Highfluxfilter

Substitute 400ml/h

Blood pump

Filtrate pump

Waste 800ml/h

SPAD :
- lowers effectively bilirubin, bile acids und ammonium in ALF - reduces hepatic encephalopathy - is well tolerated in case of SPAD System pre-filling even in a catecholamine dependant patient - stabilizes children prior to LTX and is helpful for bridging to transplantation.

Continuous Veno- Venous Single Pass Albumin Haemodiafiltration ( SPAD)
Roler pump 1
Substitute 330ml/h

Roler pump 2
Albumin 20% . 70 ml/h

Substitute pump
Highfluxfilter

Substitute 400ml/h

Blood pump

Filtrate pump

Waste 800ml/h

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