2. INTRODUCTION
• The liver is a complex organ with various vital
functions in synthesis, detoxification and
regulation; its failure therefore constitutes a
life threatening condition
3. • Liver failure (LF) can either occur without
preceding liver disease (acute liver failure,
ALF), usually caused either by intoxication
(Amanita phalloides, acetaminophen,) or as
acute decompensation of chronic liver-related
illness
4. • The only long-term therapy in most cases
is orthotopic liver transplantation, unless
the liver is able to regenerate
• Many patients, especially those who are
not listed for high urgency
transplantation, may not survive until a
suitable donor organ is available, since
donor organs are rare
5. • For these indications, extracorporeal liver
assist devices have been developed in order to
either bridge the patient to transplantation or
temporarily support the failing organ until it is
able to regenerate
6. INTRODUCTION
• Unlike renal failure, artificial support
systems were not widely used in liver
failure, mainly because hepatic
toxins are albumin-bound unlike
most uremic toxins and hence
cannot be removed by conventional
dialysis.
8. • It has been only recently that advances
have been made concerning removal of
hepatic toxins.
• It is now possible to support the patient
with liver failure till the liver recovers or
until liver transplantation is feasible
9. INDICATIONS FOR CONSIDERING ARTIFICIAL
LIVER SUPPORT SYSTEMS
–To give additional time for liver
regeneration or spontaneous recovery to
occur
–The usual situations include-
• acute fulminant hepatitis due to Hepatitis
A &b
• Liver toxicity due to acetaminophen
• severe acute alcoholic hepatitis
10. INDICATIONS
–conditions producing an acute
exacerbation of a chronic liver disease
•like a gastrointestinal bleed
•spontaneous bacterial peritonitis
and
•sepsis
11. INDICATIONS
• In hepatorenal syndrome type 1,
sudden deterioration of liver
function with acute renal failure
following precipitating events may
warrant use of ALS systems
12. INDICATIONS
• In chronic liver disease and in
hepatorenal syndrome type 2 , ALS
systems are indicated,till liver transplant
is feasible
• Following liver transplantation, ALS may
be indicated in primary non-function or
delayed function of the graft
13. TYPES OF ARTIFICIAL LIVER SUPPORT
SYSTEMS
• Support systems designed to treat patients
with liver failure have been in development
for over 30 years
• two main categories:
– Artificial or Non-cell-based:
– Bioartificial or cell-based:
14. TYPES OF ARTIFICIAL LIVER SUPPORT
SYSTEMS
Artificial or Non-cell-based:
conventional METHODS
• 1. Peritoneal dialysis
• 2. Hemodialysis
• 3. Hemofiltration (HF)
• 4. Continuous renal replacement therapy
• 5. Charcoal hemoperfusion.
• 6. Plasma exchange
15. Artificial Liver support devices (Non-
cell based liver support systems)
• Molecular Adsorbents recirculating
system (MARS)
• Fractionated plasma separation and
adsorption (prometheus)
• Single pass albumin dialysis (SPAD)
• Selective Plasma Filtration therapy
(SEPET)
16. TYPES OF ARTIFICIAL LIVER SUPPORT
SYSTEMS
• Bioartificial or cell-based:
• HepatAssist
• Extracorporeal Liver AssistDevice (ELAD)
• Bioartificial Liver support system (Blss)
• Amsterdam Medical Centre Bio-
artificial Liver (AMCBAl)
• Molecular Extracorporeal Liver Support
(Mels)
17.
18. Comparition b/n artificial and
bio-artificialliver support device
Cellular component
Hepatic functions
achieved
Cost
Ease of use
Efficacy
Artificial liver support
device
No
Detoxification only
Comparatively less
Relatively easier
Limited
Bio-artificial liver support
device
Yes
All hepatic functions
High cost for designing,
operating and managing
Complexity of maintain
living components
Expected results more
promising
Type of liver support
device
19. PERITONEAL DIALYSIS
• This has been used occasionally in
patients with combined liver and
renal failure with ascites,
• It has a limited role due to
inadequate removal of hepatic toxins
especially in those having poor
peritoneal blood flow.
20. HEMODIALYSIS
• Haemodialysis, being the common
treatment for renal failure, is also used
for treatment of patients in liver failure
to remove water soluble toxins.
• Since liver failure is often accompanied
by renal failure, haemodialysis is part of
the standard intensive care treatment
22. • Limitations :
– Majority of hepatic toxins are albumin-bound or
lipid soluble, they are not removed by HD
– Challenging hemodynamics
– Bleeding risk from acquired coagulopathy
24. HEMOFILTRATION (HF)
• Highly permeable membranes like
polysulphone or polyacrylonitrile are used to
remove fluid, including some hepatic toxins
and ammonia
25.
26. Charcoal hemoperfusion.
• Blood is passed through a cartridge
containing charcoal particles.
• Adsorbs lipid-soluble toxins and thus
is theoretically superior to HD or HF
though randomized controlled trials
have not shown any additional
benefit in prolonging survival.
28. Plasma exchange
• By using high volume plasma exchange
using highly permeable plasma filters, it
is possible to remove lipid-soluble and
albumin-bound hepatic toxins.
•
29. CONTINUOUS RENAL REPLACEMENT
THERAPY
• Use of permeable membranes with a
slower blood pump speed for prolonged
periods in hepatic encephalopathy is
associated with greater cardiovascular
and intracranial stability compared to
intermittent HD or HF
30. CONTINUOUS RENAL REPLACEMENT
THERAPY
• When an arterial line is obtained, a blood
pump is not required and is termed
continuous arteriovenous hemodialysis
(CAVHD).
• With venous lines, a pump is required
and is called continuous venovenous
hemodialysis (CVVHD).
32. CONTINUOUS RENAL REPLACEMENT
THERAPY
• This method may improve hepatic encephalopathy
by decreasing intracranial pressure, and may be
useful when sepsis is a precipitating factor by
removing inflammatory cytokines
33. CONTINUOUS RENAL REPLACEMENT
THERAPY
• Lactate based replacement fluids or
dialysate are however to be avoided
in liver failure due to defective
conversion of lactate to bicarbonate.
• Hence bicarbonate based fluids have
to be used
34. Molecular adsorbents recirculating
system (MARS)dialysis
• This is a modification of dialysis in which an
albumin based dialysate is employed with the
aim of removing albumin-bound toxins which
accumulate in liver failure
35. • The MARS system consists of three
compartments:
- a blood circuit,
-an albumin circuit and
-either a HD or HF compartment
36. • The blood circuit generally employs a veno-
venous access with a blood pump at a speed
of around 150 ml/min.
37. • Blood is passed through a special non-
albumin permeable high flux dialyzer
membrane usually made of
polysulphone, which is capable of
adsorbing albumin-bound toxins
38.
39. • The albumin circuit generally contains
about 600 ml of 20% human albumin and
is also driven by a pump at a speed of
around 150 ml/mint.
• This is passed through the dialysate
compartment of the blood dialyzer
where it removes the toxins bound to the
dialyzer membrane
40. • The dialysate is then regenerated by passing
through an activated charcoal column and
then through another column containing an
anion exchange resin
41. • In addition, water-soluble toxins are
removed from the dialysate by
passing it across a low flux HD
membrane with a bicarbonate
dialysate as in conventionalHD
• Heparin is used as anticoagulant at a
dose of 250 – 1000 IU / hr
42. • Each session is around eight hours and is
performed either daily or on alternate day.
The number of sessions is decided based on
the patient’s response
• Generaly 5 sittings may be adequate in acute
liver failure where a decrease in bilirubin,
bile acids, liver enzymes, plasma ammonia
levels as well as urea levels can occur
43. • COMPLICATIONS
• Thrombocytopenia is a common
though usually mild and
occasionally arrhythmias may occur
• The approximate cost for the
disposable items used in each
session is around 2 lakhs
44. • BENEFICIAL EFFECTS OF MARS
• decrease in mortality in type I hepatorenal
syndrome patients
• acute alcoholic hepatitis where a marked
fall in serum bilirubin can occur.
• An improvement in cardiovascular
hemodynamics and subsequent renal
function can occur.
• Improvement in encephalopathy and a
decrease in intracranial pressure and
pruritus has been shown
45. thirteen patients with cirrhosis were
divided into two groups
• A control group (n = 5)
• received standard
medical treatment
and hemodiafiltration
(HDF)
• Test group (n = 8)
additionally being
treated with MARS
along with standard
treatment
• MARS-treatment was
applied 1–10 times for
6–8 hours
According to chui le
et .al
46. • . A significant decrease in creatinine and
bilirubin levels as well as an increase in serum
sodium level and prothrombin activity was
detected in the MARS group
• Mortality of the control group reached 100%
after seven days, whereas it was at 62,5% in
the MARS group
47. Prometheus system
• Fractional plasma separation and adsorption
system creates a filtrate through 250 kDa
pore size filter.
• Unlike MARS where the membrane is
albumin-impermeable, in Prometheus, the
albumin-bound toxins diffuse across the
albumin-permeable membrane of
Prometheus.
48. Prometheus system
• The filtrate is then passed over two columns of
neutral resin and anion-exchange and then returned
to the patient.
• Thus the patient’s albumin is cleansed of the bound
toxins and no exogenous albumin is used
49.
50. PROMETHEUS
• Overall Prometheus provides higher
clearance for most liver toxins especially
if they are tightly albumin bound.
• However, for bile acids and cytokines no
such differences have been found
between MARS/prometheus.
51. Single Pass Albumin Dialysis (SPAD)
• The patient's blood also passes a high
flux dialysis membrane.
• Albumin solution streams along the
other side of the membrane counter-
directionally, accepting toxins from the
plasma.
52. • However, in SPAD the albumin solution is
discarded after a single passage of the
membrane without being recycled
53. Selective Plasma Filtration therapy
(SEPET)
• SEPET utilizes hollow-fiber with a membrane
pore size, which allows passage of molecules
with molecular weight less than 100 kDa,
thereby preserving immunoglobulins,
complement proteins, clotting factors and
hepatocyte growth factor.
54. Selective Plasma Filtration therapy
(SEPET)
• Part of the patient’s albumin is lost
due to the pore size of the filter and
has to be replaced.
• The removed fluid is replaced by
Albumin, fresh frozen plasma and
electrolytes.
• This system is currently under clinical
evaluation.
55. Bioartificial liver systems
• In this system, patient's blood or
plasma is pumped into bioreactors,
which are hollow fibre devices,
seeded on the dialysate side with
freshly isolated or cryopreserved
porcine hepatocytes or transformed
human hepatoma cell line
56. Bioartificial liver systems
• Blood initially passes through a plasma
filter and the plasma filtrate perfuses
through the bioartificial liver and is
returned to the patient after passing
through a charcoal adsorption column
57. Bioartificial liver systems
• Has the advantage of performing hepatic
synthetic functions in addition to
detoxification functions performed by
the other ALS systems.
• This have been employed in treatment
of acute liver failure and in primary non-
function of a liver transplant
58. Bioartificial liver systems
• An improvement in encephalopathy and
an increase in cerebral perfusion
pressure were noted
• The effective hepatocytes account for
only 2% of a normal hepatic function and
is hence not very successful in acute
decompensation of chronic liver disease
59. HepatAssist
• HepatAssist by Arbios was the first FDA-
approached biologically based liver assist
device.
• This employs a hollow fiber extracorporeal
bioreactor loaded with cryopreserved porcine
hepatocytes
60. EXTRCORPOREAL LIVER ASSIST
DEVICES
• In this system, blood is made to pass through
one or more hollow fibre devices containing
up to 200 gm of human hepatocytes, usually
derived from hepatoblastoma cell line, on
the dialysate side
• Patients generally tolerate the procedure
well with improvement in encephalopathy
and can be used in patients awaiting liver
transplantation.
61.
62. Modular Extracorporeal Liver support
(MELS)
• The Modular Extracorporeal Liver support
(MELS) system is based on hollow fibers
containing fresh porcine hepatocytes.
64. Bioartificial Liver Support System
(BLSS)
• Bioartificial Liver Support System
(BLSS) by Excorp Medical
(Minnesota, USA) utilizes porcine
hepatocytes in a single hollow fiber
cartridge
• It is under phase II/III studies.
65. Amsterdam Medical Center
Bioartificial Liver (AMC-BAL)
• Amsterdam Medical Center Bioartificial
Liver (AMC-BAL) utilizes porcine
hepatocytes bound to a spiral-shaped
polyester fabric with integrated hollow
fiber.
• It is under preliminary studies,….
66. Xenogenic perfusion
• Attempts to prolong life in fulminant
hepatic failure using extracorporeal
whole organ perfusion with baboon
or pig liver have not shown
significant advantage over
conventional treatment.
67. Extracorporeal hepatic perfusion
• Performing extracorporeal perfusion
using human liver not suitable for
transplantation may show a transient
improvement.
• This may hence have a role just prior
to liver transplantation.
68.
69. CONCLUSIONS
• Artificial and bioartificial liver devices
represent a potentially useful options in
management of patients with liver failure.
• While artificial liver devices have shown
improvement in biochemical parameters, the
benefit in terms of survival benefit has not
been clearly demonstrated.
70. CONCLUSIONS
• The artificial liver devices provide
detoxification alone.
• BALs provides both detoxification as well as
synthetic functions
• However, a lot of work needs to be done in
developing BAL devices and carrying out
clinical trials to demonstrate not only efficacy
but also safety
71. References
• Journal of the Association of Physicians of
India
• Medicine update 2012
• www.ncbi.nlm.nih.gov/pubmed
• Sleisenger and Fordtran’s gastrointestinal and
liver disease
