A

PAPER
PRESENTATION
ON
BIO-ARTIFICAL LIVER

YASUMREDDY SATISH(yasum_satish@yahoo.com)

M.DAYANAND
Department of Biomedical Engineering, J.B. Inst of Engg & Tech,
Hyderabad
 ABSTRACT:

The liver is the largest organ in the body and performs a variety of tasks that
impact all parts of the body. As a result, liver disease has widespread effects
on virtually all other organ systems. Remarkably, the liver is the only organ
that can regenerate itself. Numerous attempts have been made over the past
30 years to develop a technique to provide either partial or total metabolic
support for the patient with a failing liver. The technical and clinical
objective is to provide a temporary liver assist until a patient's own liver
regenerates or until a liver transplant can be performed.
No Bioartificial Liver System is commercially available today.

By using a special technique of naturally available resources like animal

cells and synthetic membrane we are able to create bio artifical liver which
performes 90% of liver functions. It will be a boon for those suffering from
liver failure.
 THE BIO-ARTIFICIAL LIVER

INTRODUCTION:

The only treatment available for liver failure is liver transplant surgery; but donor organs
are difficult to obtain, and the procedure, which is expensive and complex, is frequently
unsuccessful.
A workable artificial liver is desperately needed. Unlike the heart and the kidneys, the
liver is able to regenerate; many people who have suffered liver damage would survive if
they could be supported by an artificial liver until their own livers heal. The device could
also save the lives of hepatitis victims, and offer a means of survival for the millions of
people whose livers are in failure. And, an artificial liver could support patients awaiting
transplant surgery, or waiting for a new donor organ after a transplant has failed.
it seemed that developing an artificial liver would be impossible. The liver is an
extremely complex organ. It performs a variety of functions, and many of them are still
poorly understood. One science journalist speculated that the equipment needed to
simulate the functions of a single human liver would occupy a large office building.
Here a completely different approach to developing an artificial liver is used Instead of
trying to design mountains of equipment to perform each of the liver's functions, a device
that uses liver cells obtained from animals. Because the device contains both biological
and manufactured components, it is called a "bio-artificial liver." A patient's blood
circulates through this bio-artificial liver, where a unique synthetic membrane separates it
from the animal cells. The membrane prevents immunologic rejection of the cells, but
allows the cells to detoxify the blood in the same way as a natural liver. Disposable units
can be used for a series of brief treatments, as with kidney dialysis. Already, the bio-
artificial liver has saved the life of a man who was dying of liver failure because cancer
had blocked his bile duct.

EXISTING METHODS:

Early on, two fundamental methods used to clear toxins from the blood of patients with
liver failure were plasma exchange by apheresis and whole blood exchange transfusion. In
these procedures, toxins were removed in addition to a percentage of the blood volume.
These proved to be cumbersome and inefficient procedures for removing unspecified
toxins from the bloodstream. In the face of continuous toxin production, an exchange
procedure lasting only a few hours and affecting only a proportion of the total blood
volume was limited by the relatively small daily clearance that was ultimately achieved.It
has also been noted that certain toxins present in patients with acute, fulminant liver
failure can be cleared from the total blood volume across the treatment for hepatic
encephalopathy. In 1976 scientists developed the polyacrylonitrile (PAN) membrane. In
comparison to standard dialysis, this membrane allowed removal of higher molecular-
weight substances, in the range of 5,000 daltons, and further improved hemofiltration as a
therapy for liver failure.
Later came the liver transplant in the last decade which if makes a perfect match it
performs like a normal liver but its highly risky and as there is no supplement for it like
in kidney transplant there is a dialyses.

PRESENT METHODs,WORKING & RESEARCH :

Functions of liver:

The complex array of functions that the normal liver provides — synthesis of coagulation
factors, opsonins, albumin, and prohormones (eg, renin substrate); gluconeogenesis;
amino acid and lipid metabolism; and (via Kupffer cells and endothelium)
reticuloendothelial clearance of bacteria and small particle debris. The most difficult
hepatic function to replace exogenously is detoxification, which is accomplished
primarily through biotransformation and/or excretion of various toxic metabolites and
exogenous agents.

Two methods are discussed in designing of bio artifical liver.

1. Using synthetic membrane

2. Extra corporeal hepatitis bio reactor

The bio-artificial liver device is intended to provide temporary support to patients with
liver failure until their liver recovers spontaneously or until transplantation is possible.
The device is connected to a vein and remains outside their body. It should help remove
toxins from the patient’s own liver cells, as the patient’s blood circulates in a chamber
with pig liver cells inside polymer and synthetic membranes. The membranes allow
toxins to pass through, but prevents proteins, and other cell byproducts from the pig cells
to get into the patient’s blood.

Patients are attached to the machine by a catheter into a vein, and the blood is initially put
through a mechanical filtration process to remove some waste products. Then the blood
plasma is passed through cartridges containing the hepatic cells before being returned to
the body.

The development of hollow-fiber technology allowed for viable human or animal

hepatocytes to become an integral part of an artificial liver device and potentially
increase clearance efficiency. These devices contain the hepatocytes in a separate
chamber, isolated by a semipermeable and membrane with synthetic membrane present
in it , around which blood or plasma circulates in a manner similar to hemodialysis.
Flow through the artificial liver has four distinct steps: separation of plasma from whole
blood by filtration through a microporous membrane; removal of toxins from the
separated plasma as it passes by the functional hepatocytes in the hollow fibers;
reconstitution of the plasma with the blood in the extracorporeal circuit; and, finally,
reinfusion into the patient.
The separate chamber design allows replacement with fresh hepatocytes. Further, by
separating the hepatocytes from the bloodstream with a semipermeable membrane, the
potential for immune responses to cell surface (alloantigens or xenoantigens)

theoretically reduced. The potential exists for soluble antigens or antigenic peptides to
pass through the semipermeable barrier and initiate an immune response . {So far, this last
issue has been more theoretical than real; the gravely ill patients who have undergone
perfusion through whole animal livers have never produced anti-xenotypic antibodies.
Presumably, the likelihood of an immune response would increase as the duration of liver
support lengthened or in patients less critically ill, and this possibility would have to be
considered if such support were used as a bridge to transplantation. }

Bioartificial liver with porcine hepatocytes attached to microcarriers and placed in the
extra-fiber compartment of hollow-fiber modules

Method 2
. Extra corporeal hepatitis bio reactor

Schematic representation of blood flow

from the patient, through the plasma separator, then the bioreactor, and back to the
patient.
 Advanced Tissue Sciences has developed a technique to grow normal
human liver tissue on a three-dimensional framework of polymer mesh .Hepatocytes
adherent to the framework divide and differentiate. This liver tissue can be placed in
hollow chambers, separated from the plasma or blood by a semipermeable membrane.
The use of this system currently is limited by the ability to obtain human hepatocytes and
grow them to a sufficient mass to support hepatic function.

With a contrasting strategy, improved the function and viability of primary hepatocytes
within a bioartificial liver by avoiding attachment to the interface. They allow the
hepatocytes to circulate through the bioreactor, which is perfused with oxygenated
nutrient medium, at a rate optimal for collision and aggregation to occur. The hepatocyte
aggregates are subsequently entrapped in a packed bed of glass beads. By removing the
hepatocytes from the interface and "recharging" them periodically, Li's group has
maintained viability for up to three weeks in culture. Hepatocytes nurtured this way
resembled in vivo hepatocytes, with cuboidal shapes and intercellular contacts.
Hepatocytes cultured for 15 days in this bioreactor manifested interconnecting three-
dimensional structures resembling the sinusoidal plate. Electron microscopy revealed
plentiful mitochondria, rough and smooth endoplasmic reticulum, glycogen granules, and
desmosomes.

Because hepatocytes are not fixed to the plasma interface in Li's bioreactor, an efficient
countercurrent flow can be incorporated, greatly expanding the effective
plasma/hepatocyte contact. This, and the ability to extract "exhausted" cells from the
circuit, offer a potential advantage, possibly allowing artificial liver support to be
maintained continuously for an extended period. The technique has been tried in one
individual. The patient, a 10-year-old female with hepatitis C, awakened from hepatic
coma and recovered without liver transplantation. As with other support devices, further
human trials are eagerly awaited.

Currently, the impetus for developing a bioartificial liver is to serve as a bridge to liver
transplantation in patients with fulminant hepatic failure. It is clear that survival
posttransplant is improved if patients are transplanted before they require hospitalization
for treatment of complications of their disease. This approach is cost-effective as well.
Therefore, if the use of a bioartificial liver improved a patient's condition and allowed
recovery from some of the complications of chronic liver disease prior to transplantation,
the bioartificial liver might well prove both medically effective and economical. It might
allow patients to leave the hospital and wait at home for elective liver transplantation. It
would also end the practice of transplanting the sickest patients first, a strategy which is
very costly and results in a high incidence of retransplantation.

CONCLUSION:

As the indications for liver transplantation have expanded and as donor organs have
failed to keep pace, the need for an artificial liver has become more critical. Given that
the regenerative capacity of the liver is practically unlimited, the liver can usually recover
sufficient function to sustain life if function can be supported for a few weeks. If an
artificial liver were routinely available, many patients with liver failure might recover
without liver transplantation. In the end, bioartificial livers will probably be used as a
bridge to transplantation, to support patients with acute processes through the recovery
phase, and to improve quality of life for patients with chronic liver disease.

REFERENCES:
1.Handbook of biomedical engg..Bronzino,jeseph.

2.Artifical organs by Erie .D.Blom ,HOWARD B.ROTHMAN

3. Hench l.l ,ethridge e.c bio material ,an interfacial approach ,1982

4. The sources have been useful in the making of this paper .We are thankful
to vast information available on the WWW &the books available on the
subject.