The liver is a vital organ present in vertebrates and some other animals.

It has a wide range of

functions, including detoxification, protein synthesis, and production of biochemicals necessary
for digestion. The liver is necessary for survival; there is currently no way to compensate for the
absence of liver function in the long term, although new liver dialysis techniques can be used in
the short term.
This organ plays a major role in metabolism and has a number of functions in the body, including
glycogen storage, decomposition of red blood cells, plasma protein synthesis, hormone
production, and detoxification. It lies below the diaphragm in the abdominal-pelvic region of the
abdomen. It produces bile, an alkaline compound which aids in digestion via the emulsification
of lipids. The liver's highly specialized tissues regulate a wide variety of high-volume
biochemical reactions, including the synthesis and breakdown of small and complex molecules,
many of which are necessary for normal vital functions.[2]

Anatomy
The liver is a reddish brown organ with four lobes of unequal size and shape. A human liver
normally weighs 1.441.66 kg (3.23.7 lb),[3] and is a soft, pinkish-brown, triangular organ. It is
both the largest internal organ (the skin being the largest organ overall) and the largest gland in
the human body. It is located in the right upper quadrant of the abdominal cavity, resting just
below the diaphragm. The liver lies to the right of the stomach and overlies the gallbladder. It is
connected to two large blood vessels, one called the hepatic artery and one called the portal vein.
The hepatic artery carries blood from the aorta, whereas the portal vein carries blood containing
digested nutrients from the entire gastrointestinal tract and also from the spleen and pancreas.
These blood vessels subdivide into capillaries, which then lead to a lobule. Each lobule is made
up of millions of hepatic cells which are the basic metabolic cells. Lobules are the functional
units of the liver.

Cell types
Two major types of cells populate the liver lobes: karat parenchymal and non-parenchymal cells.
80% of the liver volume is occupied by parenchymal cells commonly referred to as hepatocytes.
Non-parenchymal cells constitute 40% of the total number of liver cells but only 6.5% of its
volume. Sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells are some of the nonparenchymal cells that line the hepatic sinusoid.[4]

Blood flow
The liver gets a dual blood supply from the hepatic portal vein and hepatic arteries. Supplying
approximately 75% of the liver's blood supply, the hepatic portal vein carries venous blood
drained from the spleen, gastrointestinal tract, and its associated organs. The hepatic arteries
supply arterial blood to the liver, accounting for the remainder of its blood flow. Oxygen is
provided from both sources; approximately half of the liver's oxygen demand is met by the
hepatic portal vein, and half is met by the hepatic arteries.[5]

Blood flows through the liver sinusoids and empties into the central vein of each lobule. The
central veins coalesce into hepatic veins, which leave the liver.

axial CT image showing anomalous hepatic veins coursing on the subcapsular anterior surface of
the liver.[6]

Maximum intensity projection (MIP) CT image as viewed anteriorly showing the anomalous
hepatic veins coursing on the anterior surface of the liver

Lateral MIP view in the same patient

Biliary flow

The biliary tree

The term biliary tree is derived from the arboreal branches of the bile ducts. The bile produced in
the liver is collected in bile canaliculi, which merge to form bile ducts. Within the liver, these
ducts are called intrahepatic (within the liver) bile ducts, and once they exit the liver they are
considered extrahepatic (outside the liver). The intrahepatic ducts eventually drain into the right
and left hepatic ducts, which merge to form the common hepatic duct. The cystic duct from the
gallbladder joins with the common hepatic duct to form the common bile duct.
Bile either drains directly into the duodenum via the common bile duct, or be temporarily stored
in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the
second part of the duodenum together at the ampulla of Vater.

Surface anatomy
Peritoneal ligaments
Apart from a patch where it connects to the diaphragm (the so-called "bare area"), the liver is
covered entirely by visceral peritoneum, a thin, double-layered membrane that reduces friction
against other organs. The peritoneum folds back on itself to form the falciform ligament and the
right and left triangular ligaments.
These "lits" are in no way related to the true anatomic ligaments in joints, and have essentially no
known functional importance, but they are easily recognizable surface landmarks. An exception
to this is the falciform ligament, which attaches the liver to the posterior portion of the anterior
body wall.
Lobes
Traditional gross anatomy divided the liver into two lobes (left and right), if viewed from the
parietal surface; but if observed on the visceral surface it is divided into four lobes with the
addition of the caudate and quadrate lobe.
The falciform ligament is visible on the front (anterior side) of the liver. This divides the liver
into a left anatomical lobe, and a right anatomical lobe.

If the liver is flipped over, to look at it from below (the visceral surface), there are two additional
lobes between the right and left. These are the caudate lobe (the more superior) and the quadrate
lobe (the more inferior).
On the visceral surface a functional anatomy dictates how the liver is organized. One must view
an imaginary line that passes to the left of the vena cava all the way forward and sections the
gallblader into two halfs. This line is called Cantlie's Line. This line divides the liver in left and
right. Other anatomical landmarks exist, such as the ligamentum venosum (ligamentum of
Arancio) and the round ligament (ligamentum Teres) that further divide the left side of the liver
in two sections. Now an important anatomical landmark, the transverse fissure of the liver
divides this left portion of the liver into four segments which will be numbered starting at the
caudate lobule as I in an anti-clock manner. From this visceral view we can see 7 segments
because the 8th segment is only visible in the parietal view. Each of the lobes is made up of
lobules; a vein goes from the centre, which then joins to the hepatic vein to carry blood out from
the liver.
On the surface of the lobules, there are ducts, veins and arteries that carry fluids to and from
them.

Functional anatomy
Correspondence between anatomic lobes and Couinaud segments
Segment*

Couinaud segments

Caudate

Lateral

2, 3

Medial

4a, 4b

Right

5, 6, 7, 8

* or lobe, in the case of the caudate lobe

Each number in the list corresponds to one in the table. 1. Caudate
2. Superior subsegment of the lateral segment
3. Inferior subsegment of the lateral segment
4a. Superior subsegment of the medial segment
4b. Inferior subsegment of the medial segment
5. Inferior subsegment of the anterior segment
6. Inferior subsegment of the posterior segment
7. Superior subsegment of the posterior segment
8. Superior subsegment of the anterior segment

The central area where the common bile duct, hepatic portal vein, and hepatic artery proper enter
is the hilum or "porta hepatis". The duct, vein, and artery divide into left and right branches, and
the portions of the liver supplied by these branches constitute the functional left and right lobes.

The functional lobes are separated by an imaginary plane (historically called Cantlie's line)
joining the gallbladder fossa to the inferior vena cava. The plane separates the liver into the true
right and left lobes. The middle hepatic vein also demarcates the true right and left lobes. The
right lobe is further divided into an anterior and posterior segment by the right hepatic vein. The
left lobe is divided into the medial and lateral segments by the left hepatic vein. The fissure for
the ligamentum teres also separates the medial and lateral segments. The medial segment is also
called the quadrate lobe. In the widely used Couinaud (or "French") system, the functional lobes
are further divided into a total of eight subsegments based on a transverse plane through the
bifurcation of the main portal vein. The caudate lobe is a separate structure which receives blood
flow from both the right- and left-sided vascular branches.[7][8]

In other animals
The liver is found in all vertebrates, and is typically the largest visceral organ. Its form varies
considerably in different species, and is largely determined by the shape and arrangement of the
surrounding organs. Nonetheless, in most species it is divided into right and left lobes;
exceptions to this general rule include snakes, where the shape of the body necessitates a simple
cigar-like form. The internal structure of the liver is broadly similar in all vertebrates.[9]
An organ sometimes referred to as a liver is found associated with the digestive tract of the
primitive chordate Amphioxus. However, this is an enzyme secreting gland, not a metabolic
organ, and it is unclear how truly homologous it is to the vertebrate liver.[9]

Physiology
The various functions of the liver are carried out by the liver cells or hepatocytes. Currently,
there is no artificial organ or device capable of emulating all the functions of the liver. Some
functions can be emulated by liver dialysis, an experimental treatment for liver failure. The liver
is thought to be responsible for up to 500 separate functions, usually in combination with other
systems and organs.

Synthesis
Further information: Proteins produced and secreted by the liver

A CT scan in which the liver and portal vein are shown.

A large part of amino acid synthesis

The liver performs several roles in carbohydrate metabolism:

o Gluconeogenesis (the synthesis of glucose from certain amino acids, lactate or
glycerol)
o Glycogenolysis (the breakdown of glycogen into glucose)
o Glycogenesis (the formation of glycogen from glucose)(muscle tissues can also do
this)

The liver is responsible for the mainstay of protein metabolism, synthesis as well as
degradation.

The liver also performs several roles in lipid metabolism:

o Cholesterol synthesis
o Lipogenesis, the production of triglycerides (fats).
o A bulk of the lipoproteins are synthesized in the liver.

The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, X and
XI, as well as protein C, protein S and antithrombin.

In the first trimester fetus, the liver is the main site of red blood cell production. By the
32nd week of gestation, the bone marrow has almost completely taken over that task.

The liver produces and excretes bile (a yellowish liquid) required for emulsifying fats and
help the absorption of vitamin K from the diet. Some of the bile drains directly into the
duodenum, and some is stored in the gallbladder.

The liver also produces insulin-like growth factor 1 (IGF-1), a polypeptide protein
hormone that plays an important role in childhood growth and continues to have anabolic
effects in adults.

The liver is a major site of thrombopoietin production. Thrombopoietin is a glycoprotein

hormone that regulates the production of platelets by the bone marrow.

Breakdown

The breakdown of insulin and other hormones

The liver glucoronidates bilirubin, facilitating its excretion into bile.

The liver breaks down or modifies toxic substances (e.g., methylation) and most
medicinal products in a process called drug metabolism. This sometimes results in
toxication, when the metabolite is more toxic than its precursor. Preferably, the toxins are
conjugated to avail excretion in bile or urine.

The liver converts ammonia to urea (urea cycle).

Other functions

The liver stores a multitude of substances, including glucose (in the form of glycogen),
vitamin A (12 years' supply), vitamin D (14 months' supply)[citation needed], vitamin B12
(13 years' supply), vitamin K, iron, and copper.

The liver is responsible for immunological effectsthe reticuloendothelial system of the

liver contains many immunologically active cells, acting as a 'sieve' for antigens carried
to it via the portal system.

The liver produces albumin, the major osmolar component of blood serum.

The liver synthesizes angiotensinogen, a hormone that is responsible for raising the blood
pressure when activated by renin, an enzyme that is released when the kidney senses low
blood pressure.

Relation to medicine and pharmacology

The oxidative capacity of the liver decreases with aging and therefore, benzodiazepines (BZDs)
that require oxidation are more likely to accumulate to toxic levels. Therefore, those with shorter

half-lives, such as lorazepam and oxazepam are preferred when benzodiazepines are required in
regards to geriatric medicine.

Diseases of the liver

Main article: Liver disease

Left lobe liver tumor

The liver supports almost every organ in the body and is vital for survival. Because of its
strategic location and multidimensional functions, the liver is also prone to many diseases.[10]
The most common include: Infections such as hepatitis A, B, C, D, E, alcohol damage, fatty
liver, cirrhosis, cancer, drug damage (particularly by acetaminophen (paracetamol) and cancer
drugs).
Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin
in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells;
normally, the liver removes bilirubin from the blood and excretes it through bile.
There are also many pediatric liver diseases including biliary atresia, alpha-1 antitrypsin
deficiency, alagille syndrome, progressive familial intrahepatic cholestasis, and Langerhans cell
histiocytosis, to name but a few.
Diseases that interfere with liver function will lead to derangement of these processes. However,
the liver has a great capacity to regenerate and has a large reserve capacity. In most cases, the
liver only produces symptoms after extensive damage.
Liver diseases may be diagnosed by liver function tests, for example, by production of acute
phase proteins.

Disease symptoms
The classic symptoms of liver damage include the following:

Pale stools occur when stercobilin, a brown pigment, is absent from the stool. Stercobilin
is derived from bilirubin metabolites produced in the liver.

Dark urine occurs when bilirubin mixes with urine

Jaundice (yellow skin and/or whites of the eyes) This is where bilirubin deposits in skin,
causing an intense itch. Itching is the most common complaint by people who have liver
failure. Often this itch cannot be relieved by drugs.

Swelling of the abdomen, ankles and feet occurs because the liver fails to make albumin.

Excessive fatigue occurs from a generalized loss of nutrients, minerals and vitamins.

Bruising and easy bleeding are other features of liver disease. The liver makes
substances which help prevent bleeding. When liver damage occurs, these substances are
no longer present and severe bleeding can occur.[11]

Diagnosis
The diagnosis of liver function is made by blood tests. Liver function tests can readily pinpoint
the extent of liver damage. If infection is suspected, then other serological tests are done.
Sometimes, one may require an ultrasound or a CT scan to produce an image of the liver.
Physical examination of the liver is not accurate in determining the extent of liver damage. It can
only reveal presence of tenderness or the size of liver, but in all cases, some type of radiological
study is required to examine it.[12]

Biopsy / scan
Damage to the liver is sometimes determined with a biopsy, particularly when the cause of liver
damage is unknown. In the 21st century they were largely replaced by high-resolution
radiographic scans. The latter do not require ultrasound guidance, lab involvement, microscopic
analysis, organ damage, pain, or patient sedation; and the results are available immediately on a
computer screen.
In a biopsy, a needle is inserted into the skin just below the rib cage and a tissue sample obtained.
The tissue is sent to the laboratory, where it is analyzed under a microscope. Sometimes, a
radiologist may assist the physician performing a liver biopsy by providing ultrasound guidance.
[13]

Regeneration
The liver is the only internal human organ capable of natural regeneration of lost tissue; as little
as 25% of a liver can regenerate into a whole liver.[14] This is, however, not true regeneration but

rather compensatory growth.[15] The lobes that are removed do not regrow and the growth of the
liver is a restoration of function, not original form. This contrasts with true regeneration where
both original function and form are restored.
This is predominantly due to the hepatocytes re-entering the cell cycle. That is, the hepatocytes
go from the quiescent G0 phase to the G1 phase and undergo mitosis. This process is activated
by the p75 receptors.[16] There is also some evidence of bipotential stem cells, called hepatic oval
cells or ovalocytes (not to be confused with oval red blood cells of ovalocytosis), which are
thought to reside in the canals of Hering. These cells can differentiate into either hepatocytes or
cholangiocytes, the latter being the cells that line the bile ducts.
Scientific and medical works about liver regeneration often refer to the Greek Titan Prometheus
who was chained to a rock in the Caucasus where, each day, his liver was devoured by an eagle,
only to grow back each night. The myth suggests the ancient Greeks knew about the livers
remarkable capacity for self-repair, however, this claim is without evidence.[17]

Liver transplantation
Main article: Liver transplantation
Human liver transplants were first performed by Thomas Starzl in the United States and Roy
Calne in Cambridge, England in 1963 and 1965, respectively.

After resection of left lobe liver tumor

Liver transplantation is the only option for those with irreversible liver failure. Most transplants
are done for chronic liver diseases leading to cirrhosis, such as chronic hepatitis C, alcoholism,
autoimmune hepatitis, and many others. Less commonly, liver transplantation is done for
fulminant hepatic failure, in which liver failure occurs over days to weeks.
Liver allografts for transplant usually come from donors who have died from fatal brain injury.
Living donor liver transplantation is a technique in which a portion of a living person's liver is
removed and used to replace the entire liver of the recipient. This was first performed in 1989 for
pediatric liver transplantation. Only 20 percent of an adult's liver (Couinaud segments 2 and 3) is
needed to serve as a liver allograft for an infant or small child.

More recently, adult-to-adult liver transplantation has been done using the donor's right hepatic
lobe, which amounts to 60 percent of the liver. Due to the ability of the liver to regenerate, both
the donor and recipient end up with normal liver function if all goes well. This procedure is more
controversial, as it entails performing a much larger operation on the donor, and indeed there
have been at least two donor deaths out of the first several hundred cases. A recent publication
has addressed the problem of donor mortality, and at least 14 cases have been found.[18] The risk
of postoperative complications (and death) is far greater in right-sided operations than that in
left-sided operations.
With the recent advances of noninvasive imaging, living liver donors usually have to undergo
imaging examinations for liver anatomy to decide if the anatomy is feasible for donation. The
evaluation is usually performed by multidetector row computed tomography (MDCT) and
magnetic resonance imaging (MRI). MDCT is good in vascular anatomy and volumetry. MRI is
used for biliary tree anatomy. Donors with very unusual vascular anatomy, which makes them
unsuitable for donation, could be screened out to avoid unnecessary operations.

MDCT image. Arterial anatomy contraindicated for liver donation

MDCT image. Portal venous anatomy contraindicated for liver donation

MDCT image. 3D image created by MDCT can clearly visualize the liver, measure the
liver volume, and plan the dissection plane to facilitate the liver transplantation
procedure.


Phase contrast CT image. Contrast is perfusing the right liver but not the left due to a left
portal vein thrombus.

Additional Images

Liver

Liver

Liver

Dissection of portal vein in right lobe of liver]]


Human embryo, 38 mm, 89 weeks.

Development
Organogenesis
The origins of the liver lie in both the ventral portion of the foregut endoderm (endoderm being
one of the 3 embryonic germ cell layers) and the constituents of the adjacent septum transversum
mesenchyme. In human embryo, the hepatic diverticulum is the tube of endoderm that extends
out from the foregut into the surrounding mesenchyme. The mesenchyme of septum transversum
induces this endoderm to proliferate, to branch, and to form the glandular epithelium of the liver.
A portion of the hepatic diverticulum (that region closest to the digestive tube) continues to
function as the drainage duct of the liver, and a branch from this duct produces the gallbladder.[19]
Besides of signals from the septum transversum mesenchyme, fibroblast growth factor from the
developing heart also contribute to hepatic competence, along with retinoic acid emanating from
the lateral plate mesoderm. The hepatic endodermal cells undergo a morphological transition
from columnar to pseudostratified resulting in thickening into the early liver bud. Their
expansion forms a population of the bipotential hepatoblasts.[20] Hepatic stellate cells are derived
from mesenchyme.[21]
After migration of hepatoblasts into the septum transversum mesenchyme, the hepatic
architecture begins to be established, with sinusoids and bile canaliculi appearing. The liver bud
separates into the lobes. The left umbilical vein becomes the ductus venosus and the right
vitelline vein becomes the portal vein. The expanding liver bud is colonized by hematopoietic
cells. The bipotential hepatoblasts begin differentiating into biliary epithelial cells and
hepatocytes. The biliary epithelial cells differentiate from hepatoblasts around portal veins, first
producing a monolayer, and then a bilayer of cuboidal cells. In ductal plate, focal dilations
emerge at points in the bilayer, become surrounded by portal mesenchyme, and undergo
tubulogenesis into intrahepatic bile ducts. Hepatoblasts not adjacent to portal veins instead
differentiate into hepatocytes and arrange into cords lined by sinudoidal epithelial cells and bile
canaliculi. Once hepatoblasts are specified into hepatocytes and undergo further expansion, they
begin acquiring the functions of a mature hepatocyte, and eventually mature hepatocytes appear
as highly polarized epithelial cells with abundant glycogen accumulation. In the adult liver,
hepatocytes are not equivalent, with position along the portocentrovenular axis within a liver
lobule dictating expression of metabolic genes involved in drug metabolism, carbohydrate
metabolism, ammonia detoxification, and bile production and secretion. WNT/-catenin has now
been identified to be playing a key role in this phenomenon.[20]

Fetal blood supply

In the growing fetus, a major source of blood to the liver is the umbilical vein which supplies
nutrients to the growing fetus. The umbilical vein enters the abdomen at the umbilicus, and
passes upward along the free margin of the falciform ligament of the liver to the inferior surface
of the liver. There it joins with the left branch of the portal vein. The ductus venosus carries
blood from the left portal vein to the left hepatic vein and then to the inferior vena cava, allowing
placental blood to bypass the liver.
In the fetus, the liver develops throughout normal gestation, and does not perform the normal
filtration of the infant liver. The liver does not perform digestive processes because the fetus does
not consume meals directly, but receives nourishment from the mother via the placenta. The fetal
liver releases some blood stem cells that migrate to the fetal thymus, so initially the lymphocytes,
called T-cells, are created from fetal liver stem cells. Once the fetus is delivered, the formation of
blood stem cells in infants shifts to the red bone marrow.
After birth, the umbilical vein and ductus venosus are completely obliterated in two to five days;
the former becomes the ligamentum teres and the latter becomes the ligamentum venosum. In the
disease state of cirrhosis and portal hypertension, the umbilical vein can open up again.

As food
Main article: Liver (food)

Cultural allusions
In Greek mythology, Prometheus was punished by the gods for revealing fire to humans, by
being chained to a rock where a vulture (or an eagle) would peck out his liver, which would
regenerate overnight. (The liver is the only human internal organ that actually can regenerate
itself to a significant extent.) Many ancient peoples of the Near East and Mediterranean areas
practiced a type of divination called haruspicy, where they tried to obtain information by
examining the livers of sheep and other animals.
In Plato, and in later physiology, the liver was thought to be the seat of the darkest emotions
(specifically wrath, jealousy and greed) which drive men to action.[22] The Talmud (tractate
Berakhot 61b) refers to the liver as the seat of anger, with the gallbladder counteracting this.
The Persian, Urdu, and Hindi languages ( or or jigar) refer to the liver in figurative
speech to indicate courage and strong feelings, or "their best"; e.g., "This Mecca has thrown to
you the pieces of its liver!".[23] The term jan e jigar, literally "the strength (power) of my liver", is
a term of endearment in Urdu. In Persian slang, jigar is used as an adjective for any object which
is desirable, especially women. In the Zulu language, the word for liver (isibindi) is the same as
the word for courage.
The legend of Liver-Eating Johnson says that he would cut out and eat the liver of each man
killed after dinner.

In the motion picture The Message, Hind bint Utbah is implied or portrayed eating the liver of
Hamza ibn Abd al-Muttalib during the Battle of Uhud. Although there are narrations that
suggest that Hind did "taste", rather than eat, the liver of Hamza, the authenticity of these
narrations have to be questioned.

Bioartificial liver device

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A bioartificial liver device (BAL) is an artificial extracorporeal supportive device for an

individual who is suffering from acute liver failure.
Contents

1 Use

2 Function
o

2.1 Hollow fiber system

3 Comparison to liver dialysis

4 See also

5 References

Use

The purpose of BAL-type devices, currently, is not to permanently replace liver functions, but to
serve as a supportive device,[1] either allowing the liver to regenerate properly upon acute liver
failure, or to bridge the individual's liver functions until a transplant is possible.
Function

BALs are essentially bioreactors, with embedded hepatocytes (liver cells) that perform the
functions of a normal liver. They process oxygenated blood plasma, which is separated from the
other blood constituents.[2] Several types of BALs are being developed, including hollow fiber
systems and flat membrane sheet systems.[3]
Hollow fiber system

One type of BAL is similar to kidney dialysis systems that employ a hollow fiber cartridge.
Hepatocytes are suspended in a gel solution, such as collagen, which is injected into a series of
hollow fibers. In the case of collagen, the suspension is then gelled within the fibers, usually by a

temperature change. The hepatocytes then contract the gel by their attachment to the collagen
matrix, reducing the volume of the suspension and creating a flow space within the fibers.
Nutrient media is circulated through the fibers to sustain the cells. During use, plasma is
removed from the patients blood. The patient's plasma is fed into the space surrounding the
fibers. The fibers, which are composed of a semi-permeable membrane, facilitate transfer of
toxins, nutrients and other chemicals between the blood and the suspended cells. The membrane
also keeps immune bodies, such as immunoglobulins, from passing to the cells to prevent an
immune system rejection.[4]
Comparison to liver dialysis

The advantages of using a BAL, over other dialysis-type devices (e.g. liver dialysis), is that
metabolic functions (such as lipid and plasma lipoprotein synthesis, regulation of carbohydrate
homeostasis, production of serum albumin and clotting factors, etc.), in addition to
detoxification, can be replicated without the use of multiple devices. There are currently several
BAL devices currently in clinical trials.
A series of studies in 2004 showed that a BAL device reduced mortality by about half in acute
liver failure cases.[5] The studies, which covered 171 patients in the U.S. and Europe, compared
standard supportive care to the use of a bioreactor device using pig liver cells.
Liver dialysis is a detoxification treatment for liver failure and has shown promise for patients
with hepatorenal syndrome. It is similar to hemodialysis and based on the same principles. Like a
bioartificial liver device, it is a form of artificial extracorporeal liver support.
A critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared
by the failing liver. Based on this hypothesis, the removal of lipophilic, albumin-bound
substances such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty
acids and cytokines should be beneficial to the clinical course of a patient in liver failure. This
led to the development of artificial filtration and adsorption devices.
Hemodialysis is used for renal failure and primarily removes water soluble toxins, however it
does not remove toxins bound to albumin that accumulate in liver failure.

Contents

1 Liver dialysis prognosis/survival

2 Liver dialysis devices

o 2.1 Molecular Adsorbents Recirculation System (MARS)

o 2.2 Single Pass Albumin Dialysis (SPAD)

o 2.3 Comparing SPAD, MARS and CVVHDF
o 2.4 Prometheus

3 See also

4 References

5 External links
o 5.1 MARS
o 5.2 SPAD
o 5.3 Prometheus

Liver dialysis prognosis/survival

While the technique is in its infancy, the prognosis of patients with liver failure remains guarded.
Liver dialysis, currently, is only considered to be a bridge to transplantation or liver regeneration
(in the case of acute liver failure)[1][2][3] and, unlike kidney dialysis (for renal failure), cannot
support a patient for an extended period of time (months to years).

Liver dialysis devices

Artificial detoxification devices currently under clinical evaluation include the Molecular
Adsorbent Recirculating System (MARS), Single Pass Albumin Dialysis (SPAD) and the
Prometheus system.

Molecular Adsorbents Recirculation System (MARS)

The Molecular Adsorbents Recirculation System (MARS), has been developed at the
University of Rostock in Germany.It was originally produced by Teraklin AG which was
acquired by Gambro in 2004. MARS is the best known extracorporal liver dialysis system and
has existed for approximately ten years. It consists of two separate dialysis circuits. The first
circuit consists of human serum albumin, is in contact with the patient's blood through a
semipermeable membrane and has two special filters to clean the albumin after it has absorbed
toxins from the patient's blood. The second circuit consists of a hemodialysis machine and is
used to clean the albumin in the first circuit, before it is recirculated to the semipermeable

membrane in contact with the patient's blood. The MARS system can remove a number of
toxins, including ammonia, bile acids, bilirubin, copper, iron and phenols.
MARS has 510 (k) approval from the Food and Drug Administration (FDA) for drug overdoses
and poisoning as of June 2005 and is available in the USA since the end of 2005.[1] Canada's
first MARS unit arrived at the Toronto General Hospital in 2005.

Single Pass Albumin Dialysis (SPAD)

Single pass albumin dialysis (SPAD) is a simple method of albumin dialysis using standard
renal replacement therapy machines without an additional perfusion pump system: The patients
blood flows through a circuit with a high-flux hollow fiber hemodiafilter, identical to that used in
the MARS system. The other side of this membrane is cleansed with an albumin solution in
counter-directional flow, which is discarded after passing the filter. Hemodialysis can be
performed in the first circuit via the same high-flux hollow fibers.

Comparing SPAD, MARS and CVVHDF

SPAD, MARS and continuous veno-venous haemodiafiltration (CVVHDF) were compared in
vitro with regard to detoxification capacity.[4] SPAD and CVVHDF showed a significantly
greater reduction of ammonia compared with MARS. No significant differences could be
observed between SPAD, MARS and CVVHDF concerning other water-soluble substances.
However, SPAD enabled a significantly greater bilirubin reduction than MARS. Bilirubin serves
as an important marker substance for albumin-bound (non water-soluble) substances. Concerning
the reduction of bile acids no significant differences between SPAD and MARS were seen. It was
concluded that the detoxification capacity of SPAD is similar or even higher when compared
with the more sophisticated, more complex and hence more expensive MARS.
As albumin dialysis is a costly procedure, financial aspects are important: For a seven-hour
treatment with MARS, approximately 300 for 600 ml human serum albumin solution (20%),
1740 for a MARS treatment kit and 125 for disposables used by the dialysis machine have to
be spent. The cost of this therapy adds up to approximately 2165. Performing SPAD according
to the protocol by Sauer et al., however, requires 1000 ml of human albumin solution (20%) at a
cost of 500. A high-flux dialyzer costing approximately 40 and the tubings ( 125) must also
be purchased. The overall costs of a SPAD treatment is approximately 65630% of the costs of
an equally efficient MARS therapy session. The expenditure for the MARS monitor necessary to
operate the MARS disposables is not included in this calculation.

Prometheus
The Prometheus system (Fresenius Medical Care, Bad Homburg, Germany) is a new device
based on the combination of albumin adsorption with high-flux hemodialysis after selective
filtration of the albumin fraction through a specific polysulfon filter (AlbuFlow). It has been
studied[5] in a group of eleven patients with hepatorenal syndrome (acute-on-chronic liver failure
and accompanying renal failure). The treatment for two consecutive days for more than four
hours significantly improved serum levels of conjugated bilirubin, bile acids, ammonia,

cholinesterase, creatinine, urea and blood pH. Prometheus was proven to be a safe supportive
therapy for patients with liver failure.