Prepared in May 2004. Basic information about liver and its function, in addition to applications of bio-artificial liver, as an alternative for liver transplant.

1. Bioartificial
Livers
Done by : Ibrahim Al-Tayyan
Prepared in May 2004

2. Liver’s characteristics:
•Liver is a very complex organ that performs a
variety of life maintaining functions
•It weighs around 1500 grams
•It is one of the main organs in the digestive
system
•It is the 3rd most important organ in the body
after the heart and the brain.

3. Liver’s characteristics:
•The hepatic artery is the artery which is
responsible for supplying the liver with O2
while the hepatic vein takes up CO2 from the
liver cells
•Hepatocytes: are the basic functional
cellular units of the liver
•1 hepatocyte = 25 μm
•There are 250 billions of them in the liver
and they acount for 75% of the liver volume

4. Liver’s functions
•Liver has a huge number of functions,
mainly in biochemical substances
metabolism, storage, converting chemicals
into other forms and excretion of toxic
materials.
• It has a role in carbohydrates
metabolism including the storage of excess
glucose as glycogen and releasing this
material when the blood glucose level is low

5. Liver’s functions
• It also converts galactose and fructose to
glucose
• It is responsible for the body’s ability to
derive energy from fats
• It has the ability to convert carbohydrates
and proteins into fat.
•It synthesizes cholesterol and phospholipids
and forms lipoprotein which is a carrier
molecule used for transporting fats to other
tissues throughout the body

6. Liver’s functions
• It has a role in deamination of amino acids
and converts them into carbohydrates or
fats. It also uses amino acids as a source of
energy.
• Deamination of amino acids produces large
amounts of ammonia, so the liver converts
ammonia into urea
• It produces plasma proteins including the
albumin, and substances responsible for
blood clotting

7. Liver’s functions
• It also provides a storage for vitamins and
iron and they are stored as ferritin ( a protein
complex)
• It has a major role in detoxification of
materials such as drugs, environmental toxins
and some hormones
• It has an ability to detoxify harmful
substances that are absorbed from the
gastrointestinal tract

8. Liver failure
• The liver is one of the only organs that has
an ability to regenerate itself after a tissue
damage occurs
• However, if the tissue damage rate is high,
then the ability to regenerate the tissues is
low, leading to a liver failure.
• There are 2 types of liver failure: cirrhosis
and fulminant hepatic failure
• The main causes of hepatic failure are
alcoholism, chronic and viral hepatitis

9. Liver failure
• Hepatic failure causes the following:
1) Build up of toxins
2) Overactivity of hormonal system
3)Accumulation of ammonia in the plasma
4) Decreased levels of albumin and blood
clotting proteins
5) In addition to brain damage, coma and
death

10. General artificial liver
systems• The only long-term treatment is transplantation, but
because of shortage of donors, an artificial liver may
be used until an organ is available for transplantation
• Therefore, the primary goal of such liver systems is
to maintain the patient status stable, until a liver
transplant is available
• There are many difficulties facing biomedical engineers
in developing an artificial liver, since the liver has a
various number of functions.

11. General artificial liver
systems• The first approach was to develop a system
that minimizes the build up of toxins
• Such approaches are: hemodialysis,
hemoperfusion & immobilized enzyme reactors
• Hemodialysis systems are very similar to
those used in kidney dialysis, but the
membranes used have a higher molecular
weight cutoff to provide passage for large toxic
materials, but it is not effective in removing
large protein bound toxins

12. General artificial liver
systems• Hemoperfusion: it is employing beds of
activated carbon that adsorb the toxic
molecules•Unfortunately it removes beneficial substances
• Immobilized enzyme reactors uses liver
enzymes to provide more specific removal of
toxic materials but difficulty arises in
providing a complete set of these enzymes
• Anyway, those three systems do not restore
any of the synthetic functions of the liver

13. General artificial liver
systems• Other approaches for artificial liver
systems are reducing the level of toxins and
restore substances synthesized by the liver
• Such methods includes: plasma exchange,
cross circulation, extra corporeal perfusion,
cross hemodialysis & hepatocyte
hemoperfusion
• Plasma exchange: replacing the patient’s
plasma with donor plasma, but it is very risky

14. General artificial liver
systems• Cross circulation: connecting the patient’s
circulation to that of other human, who has
a healthy liver that is shared. Still it is risky
• All of these methods are risky and do not
restore any of the synthetic functions
• Scientists & biomedical engineers are
looking for the use of isolated hepatocytes
for the development of bioartificial liver

15. The development of bioartificial
livers
• Engineers and scientists are focusing on
developing bioartificial livers using isolated
hepatocytes, and they are used in both
implantable and extracorporeal systems
• Implantable systems are designed by the
basic techniques used for tissue engineering
• These isolated heptocytes should be
attached to anything, providing
immunoprotection to these cells.

16. The development of bioartificial
livers
• The mass of hepatocyte that is needed is
estimated to be around 10% of the original
liver mass.
• In implantable systems, the attachment
of hepatocytes to a support structure will
increase the device’s volume and that is
considered a big problem
•Extracorporeal systems are a better
approach for providing temporary liver
functions, but still the cells used should be
immunoprotected

17. Extracorporeal livers types
• 3 compartment hollow-fiber bioartificial liver
• HepatAssist, developed by W.R Grace & CO
•ELAD and other types

21. ELAD bioartifical liver
• It is a hollow-fiber device that uses a cloned
human cell line in place of hepatocytes
• The cells are derived from an
hepatoblastoma & selected for liver specific
functions.
• Such cells are capable of synthesizing
protein, urea & glucose, and are also capable
of detoxifying substances by a system called
the P-450 cytochrome system

22. ELAD bioartifical liver
• Such cell lines provide unlimited supply of cells
and minimize the immune problems
• 2g of cells are seed inside the fiber to
produce 200g of them. This quantity of cells
are capable of producing levels of plasma
protein e.g. it can produce 5g of albumin daily
• As it is seen on the ELAD diagram, blood
flows into a hemodialysis & mixed with
heparine to prevent blood clotting.

23. ELAD bioartifical liver
• Some of the blood passes to the ELAD
and the other portion goes into the ultra
filtration part.
• This design was tested with dogs with
fulminant hepatic failure, and it had
provided rapid improvement in blood
chemistry

24. HepatitAssist System
• This system consists of many components,
the first component where the blood flows is
the plasmapheresis, where a plasma stream
is formed from the arterial blood
• This stream enters a high flow
recirculation loop that forms the core of
the artificial liver
• Within this loop, the plasma enters a
column loaded with activated cellulose-
coated charcoal

25. HepatitAssist System
• It is used to enhance the detoxification
ability of the overall system and protect
the hepatocytes from any toxic material
• The plasma then enters a membrane
oxygenator to ensure an adequate supply of
oxygen to maintain the viability & function
of the hepatocytes

26. HepatitAssist System
• The plasma then flows through the
hollow-fiber lumens
• The plasma then exits the lumens, and
combines with the cellular components of
blood & return to the body

27. Conclusion
• Liver is a very important organ in our body
• Liver transplant is the only treatment for
hepatic failure
• Bioartificial liver is used temporarily until a
donor is available
• The first approach for designing bioartifical
livers is detoxifying toxic materials
• Any bioartificial liver consists of different
small systems like hemodialysis.

28. Conclusion
• Engineers are aiming to produce bioartifical
livers that do almost the main functions of the
liver.
• Still all of the bioartifical livers have many
limitations & problems and they are not
considered a replacement to a bioartifical liver