liver assist devices

1. LIVER ASSIST DEVICES
Dr Nibin

3. • Hepatic failure It is a clinical syndrome
resulting from massive necrosis of
hepatocytes or from severe functional
impairment of hepatocytes and liver is no
longer able to do function

4. Etiology

5. LIVER ASSIST DEVICES
• Temporary liver support systems – bridge for
the patient to transplantation or regeneration

6. • An ideal liver support device would eliminate
the need for transplantation and may offer
clinical replacement for end stage liver disease
• Ideal devices are still far from realization

7. Why Artificial Liver Support
• Liver transplantation is the only definitive
therapy for liver failure
• But
1. Limited availability of donors
2. High cost
3. Limited access

8. Expected functions are
• Detoxificaton
• Synthesis of clinically important proteins
• Facilitation of regeneration of native
hepatocytes

9. Renal vs Liver Dialysis
Renal
- Filters non protein bound
water soluble substances
- Simple diffusion across a
semi permeable
membrane
Liver
– Removes protein
bound hydrophobic
substances

10. GROUPS
• 1. ARTIFICIAL LIVER SUPPORT DEVICES (NON
CELL BASED SYSTEMS) NON BIOLOGIC
• 2. BIOARTIFICIAL LIVER SUPPORT
DEVICES(CELL BASED SYSTEMS) BIOLOGIC

11. NON BIOLOGIC SYSTEMS
• Based on the concept of albumin dialysis
• Capable of removing albumin bound toxins
which accumulate in liver failure
• Can also remove water soluble substances like
NH3, creatinine , urea, some cytokines, and
also bilirubin, protoporphyrins, bile acids

12. • Exogenous albumin
added to the dialysate
for removal of albumin
bound toxins
• Eg:-MARS,SPAD
Using large pore filters which
retain cellular components
and separate plasma proteins
including albumin.
No exogenous albumin added.
This filtrate undergoes
readsorption to clean the
toxin attached albumin.
Eg:- Promethus , SEPET
NON BIOLOGIC SYSTEMS

13. MOLECULAR ADSORBANT
RECIRCULATING SYSTEM (MARS)
• 1990s in Germany
• Cell free system that uses albumin enriched
dialysate to facilitate the removal of toxins.
• Two circuits- blood circuit and secondary
circuit
• Simultaneous liver and kidney detoxification

14. Toxins
exchange
across the
MARS
membrane
to albumin
polysulphone
and
polyamide
minimal thickness
- high density of pores
- pore size smaller than
that of albumin
The ratio of toxin to
albumin in blood to
that in dialysate
fluid determines the
gradient

15. MARS
1.
1.Dialysate
membrane:
water soluble
toxin
2.Charcoal: non-ionised
albumin bound toxins
Anion-exchanger
resin: ionised albumin
bound toxins
Albumin dialysate is
then purified in 3 steps

16. Transmembrane Gradient
• Unlike renal dialysis the toxin gradient across
membrane is not the driving force for exchange
• The ratio of toxin to albumin in blood to that in
dialysate fluid determines the gradient
• Gradient determines transport rate
• With time gradient declines

18. Substances Cleared after MARS
Ammonia
Creatinine
Urea
Aromatic amino acids
Indoles
Typtophans
Mercaptans
Nitric oxide
Endogenous benzodiazepines
Pro-inflammatory cytokine
Bile acid & bilirubin
WATER SOLUBLE
ALBUMIN BOUND

19. Adverse Effects of MARS Therapy
• Hypoglycemia
• Non-cardiogenic pulmonary edema
• Hypotension
• Thrombocytopenia
• Hemolytic anemia

20. SPAD -Single-pass albumin dialysis
simple technique of blood
purification
intensive care unit
blood is passed across and dialyzed through a high-flux
hollow-fiber hemodiafilter containing albumin
impregnated dialysate
Dialysate is discarded once it
passes through the dialyzer--
more expensive

21. • It has ease administration as compared to
MARS
• But disadvantage
standard albumin dialysate concentration,
dialysate flow rate, and standard of care are
not yet fully established.

22. Fractionated plasma separation and
adsorption—FPSA (Prometheus)
• Endogenous albumin to pass through the circuit
using the AlbuFow filter (molecular cut-off of300
kDa)
• Albumin is reactivated and returned to circulation
using a neutral resin adsorber (Prometh 01) and
an anion-exchange column (Prometh 02).
• Then patient’s blood then passes through a
second circuit, where it is treated by conventional
high-flux hemodialysis  returning blood to the
patient

24. • Filtrate through 300kDa pore size filter
• Albumin permeable membrane
• Filtrate is passed over two columns of neutral
resin and anion exchange and then passed to
the patient
• No exogenous albumin used
• Higher clearance of tightly albumin bound
toxins

25. SEPET
• Hollow fibre with membrane pore size which
allows passage of molecules with molecular
weight less than 100 kDa
• Preserving immunoglobulins, complement
proteins, clotting factors and hepatocyte
growth factor

27. • Significant decline biochemical parameters
• Improve the complications of HE due to the
removal of amino acids such as glutamine,
phenylamine, tyrosine, and tryptophan
• Significant reduction in most cytokines and
tumor necrosis factor
• significant surge in hepatocyte growth factor
(HGF) concentration, which stimulates liver
regeneration

28. BIOLOGICAL SYSTEMS
• The lack of survival benefit of artificial systems
highlights the importance of BALs
• Aim is to provide both detoxification and
synthetic functions.
• Perfusion of the patient’s blood through a
catridge containing liver cell lines or porcine
hepatocytes

29. • Human hepatocytes-
lack of availability,
do not readily regenerate in vitro
decreased efficacy when cultured
• Alternatives –
immortal cell lines like human hepatoblastoma cells
porcine hepatocytes
( potential oncogenicity)

30. TYPES
BAL
HEPAT ASSIST
EXTRACORPOREAL LIVER ASSIST DEVICE(ELAD)
human hepatocyte based
BIOARTIFICIAL LIVER SUPPORT SYSTEM(BLSS)
AMSTERDAM MEDICAL CENTRE BIO ART
LIVER(AMCBAL)
MODULAR EXTRACORPOREAL LIVER
SUPPORT(MELS)

31. BIOARTIFICIAL LIVER
Liver cells obtained from an animal or
human are suspended in a solution and
patient’s blood is processed by a
semipermeable membrane that allow
toxins and blood proteins to pass but
restricts an immunological response

32. HEPATASSIST
FIRST FDA APPROVED BIOSYSTEM
• Hollow fibre system using cryopreserved
porcine hepatocytes.
• patient’s blood is initially separated into
plasma and cellular components.

33. • The plasma is then passed through a high-flow
plasma circulation loop  charcoal filter,
oxygenator, heater  hollow fiber bioreactor
containing 7 billion cryopreserved hepatocytes
• processed plasma then combines again with
the cellular components and sent back to the
patient’s blood
• improvement in survival rate in patients

34. Extracorporeal liver assist device
(ELAD)
• consists of hepatoblastoma C3A cell line,
derived from human hepatoblastoma cell line
• Cells are localized in the extra capillary space
of a modified dialysis cartridge with a
membrane cut-off of 70 kDa to prevent
filtration of immunoglobulins, blood cells, and
C3A tumorigenic cells

35. Modular extracorporeal liver support
(MELS)
• Modular extracorporeal liver support (MELS)
was developed in Germany
• Hollow fibre containing fresh porcine
hepatocytes
• Based on tailoring the extracorporeal therapy
units to the clinical need of the patient.
• limitations are its high cost and complicated
design, which may become an obstacle for its
wide availability

36. Academic Medical Center
(Amsterdam)-BAL
• In contrary to other BAL support devices, this
modality is incorporated with capillaries for
oxygenation and viability
• When comparing MELS to AMC-BAL, both
have shown comparable efficiency.

37. • Several other liver support devices have been
developed
• Hybrid-BAL (Nanjing, China)
• TECA-Hybrid Artificial Liver Support System
(Beijing, China)
• Bioartificial Hepatic Support (Udine, Italy)
• Radial Flow Bioreactor (Ferrara, Italy),

38. ARTIFICIAL BAL
CELLULAR COMP NO YES
HEPATIC FNS DETOXIFICATION ALL HEPATIC FNS
COST LESS HIGH
EASE OF USE EASIER COMPLEX
EFFICACY LIMITED MORE PROMISING

39. TYPES
ARTIFICIAL BAL
MOLECULAR ADSORBANT
RECIRCULATING SYSTEM(MARS)
HEPAT ASSIST
FRACTIONATED PLASMA SEPARATION
AND ADSORPTION(PROMETHEUS)
EXTRACORPOREAL LIVER ASSIST
DEVICE(ELAD)
SINGLE PASS ALBUMIN DIALYSIS(SPAD) BIOARTIFICIAL LIVER SUPPORT
SYSTEM(BLSS)
SELECTIVE PLASMA FILTRATION
THERAPY(SEPET)
AMSTERDAM MEDICAL CENTRE BIO ART
LIVER(AMCBAL)
MOULAR EXTRACORPOREAL LIVER
SUPPORT(MELS)

40. THANK YOU