liver support systems

8/14/2019 liver support systems

1/27

Hanan Fathy


2/27

Toxins: Bile acids

Bilirubin

Prostacyclins

Nitric oxide

Indol / Phenol-

Metabolites

Toxic fatty acids

Thiols Digoxin/Diazepam-

like subs.

...

Ammonia

Lactate

Further liver damage

via vicious cycle:

necrosis/apoptosis !!!

Brain Function Kidney Function

Cardiovascular Tone Bone Marrow Activity

Liver failure - endogenous

intoxication

OngoingOngoing

ImbalanceImbalance

ofof

water-solublewater-soluble

andand

non-solublenon-solublesubstancessubstances


3/27

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 potentiallybound 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


4/27


5/27

Liver support therapy

Balance ofwater-solublesubstances

Balance ofprotein bound

substances

Dialysis Albumin Dialysis

Water based human body

Diffusion

Plasma exchange

(unselective)

Binding site

related distribution

Filtration

(unselective)

water-solubletoxins

(free)

non water-solubletoxins

(protein bound)

Toxin removal


6/27

Liver support systems can be divided into two

main groups:

Non biologic liver support.

Biologic liver support.


7/27


8/27

Millis JM and Losanoff JE (2005) Technology Insight: liver support systemsNat Clin Pract Gastroenterol Hepatol2: 398405 doi:10.1038/ncpgasthep0254

Biologic liver support


9/27

Millis JM and Losanoff JE (2005) Technology Insight: liver support systemsNat Clin Pract Gastroenterol Hepatol2: 398405 doi:10.1038/ncpgasthep0254

Nonbiologic liver support


10/27

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.

Liver Support Systems


11/27


12/27

Non-Biological Filtration

Techniques

Albumin dialysis pumps the blood out of thebody and into a plastic tube filled with hollow

fibers made of a membrane that has beencoated with albumin.

On one side of the fiber's membrane is theblood; on the other, a dialysis solution

containing more albumin.


13/27


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 formolecules to attach.

Then, the albumin on the membrane passes the

toxins along to the albumin in the solution as it

flows by.


14/27


Techniques

Meanwhile, smaller toxin molecules thatdon't stick to albumin flow through the

membrane's tiny pores into the less-concentrated dialysis solution.

The patient's own albumin, too large to fit

through the membrane's pores, returns tothe body with the blood.


15/27

P

atie

nt

High

-f

lux

D

Hig

h-flux

DHigh

-f

lux

D

High

-f

lux

DFiltrate

recirculation

circuit

Low-flux D

Albumin20%

600ml

MARS

MARSMARS


16/27

The MARS principle


17/27

The MARS membrane


18/27

MARS Absorber cartridges

Activated charcoal

column

(diaMARS AC250)

Anion-exchanger

resin column



19/27

Among the toxins that MARS can remove are:

Bile acids

Bilirubin

Aromatic aminoacidsPhenols

Mercaptans

Dioxin like substancesTryptophan


Short and middle chain fatty

acids Benzodiazepine like

substances Nitric oxide Ammonia Creatinine Urea

Copper Iron


20/27

20

Prometheus Circuit

Hemodialysis and liver dialysis (2 systems in 1)

Prometh 01column contains highly

porousneutral resinfor 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 02column contains anion

exchange resins with spongy inner

portions to increase surface area. It

containspositively charged ligands

capable of binding negatively charged

substances ex: unconjugated bilirubin


21/27

21

Liver Support Therapy: Prometheus Machines

PrometheusCitrate

PrometheusHeparin

Prometheus: Hemodialysis & Liver Dialysis


22/27

Toxin Elimination

Toxins Damage Elimination

Ammonia Hepat. Encephalopathy Dialysis

Creatinin, urea Kidney failure (HRS) Dialysis

Bilirubin Hepat. Encephalopathy Dialysis/02Benzodiazepine Hepat. Encephalopathy prometh01

Arom. amino acids Hepat. Encephalopathy prometh01

Bile acids Pruritus prometh01

Nitrogen oxide Hemodyn. Instability prometh 01Indols, phenols Hepat. Encephalopathy prometh01

waterwater

solublesoluble

albuminalbumin

boundbound

The Livers Poison Cabinet


23/27

In-vivo comparisons of both systemsshowed :

significantly higher extraction capacities

for protein-bound and water-solublesubstances under Prometheus thanunder MARS treatment.


24/27

Continuous Veno- Venous Single Pass

Albumin Haemodiafiltration ( SPAD)

Albumin 20%

. 70 ml/h

Roler pump 1

Filtrate pump

Substitute

400ml/h

Highfluxfilter

Waste

800ml/h

Substitute

330ml/h

Roler pump 2

Substitute pump

Blood pump


25/27

SPAD :

- lowers effectively bilirubin, bile acids undammonium in ALF

- reduces hepatic encephalopathy

- is well tolerated in case of SPAD System pre-fillingeven in a catecholamine dependant patient

- stabilizes children prior to LTX and is helpful forbridging to transplantation.


26/27

Continuous Veno- Venous Single Pass

Albumin Haemodiafiltration ( SPAD)

Albumin 20%

. 70 ml/h

Roler pump 1

Filtrate pump

Substitute

400ml/h

Highflu

xfilter

Waste

800ml/h

Substitute

330ml/h

Roler pump 2

Substitute pump

Blood pump


27/27

liver support systems

Documents