MARS

Molecular Adsorbent Recirculation System

(MARS) for liver failure: Controversies and
Evidence

Dr Alexander Chiu
Associate consultant, Honorary assistant professor
Adult Intensive care unit, Queen Mary Hospital
MRCP (UK), FHKAM (critcal care)

MARS circuit

before treatment

after treatment
 MARS: World statistics Indication: hyperbilirubinemia

• There is no consensus as to what bilirubin level should

MARS treatment be started
• Pre-treatment bilirubin threshold differs widely among
different studies from 150umol/L to 340umol/L
• Studies that compare the bilirubin level between survivors
and non-survivors from MARS treatment revealed no
differences
• The bilirubin reduction varies directly with the pre-
treatment bilirubin level
International MARS Registry
Annual Report 2005
6

Bilirubin reduction and pre dialysis bilirubin level

Hyperbilirubinemia
• Delta bilirubin and covalent-bonded bilirubin are
r2=0.585, p<0.001
formed when serum bilirubin are high.
Weiss JS etal. N Engl J Med 1983;309:147-150.

• High plasma bilirubin level will force bilirubin

molecule into tissue and the redistribution from
such depot is a constant phenomenon after
MARS treatment

Chiu A, Chan LM, Fan ST.

Molecular adsorbent recirculating system treatment for patients with liver failure: the Hong Kong experience.
7
Liver Int. 2006 Aug;26(6):695-702. 8
Bilirubin reduction and post treatment Bilirubin reduction
rebound
• Bilirubin is only a surrogate marker for other albumin
bound putative toxins. The removal rate of total bilirubin
was significantly lower when compared to bile acids (28.2
± 3.9 vs 55.4 ± 4.0%)

Evenepoel P, etal. Blood Purif. 2003;21(3):244-52.

• Removal of bilirubin increase the free binding capacity at

the surface of the albumin which could decrease the
concentration of free toxic metabolites via binding to
serum albumin.
Mitzner S et al. J Am Soc Nephrol 2001;12 S17:S75-82
Chiu A, Chan LM, Fan ST. Mitzner S, et al. Nephrol Dial Transplant 14: A201, 1999
Molecular adsorbent recirculating system treatment for patients with liver failure: the Hong Kong experience.
9
Liver Int. 2006 Aug;26(6):695-702. 10

Albumin binding capacity MARS and hepatic encephalopathy

• Stange et al reported a statistical significant improvement in
HE grades in liver failure patients from 2.82 ±0.95 to 0.75 ±
0.61 after MARS treatment

Stange J et al. Artif Organs. 1999 Apr;23(4):319-30.

• Heemann reported a significantly lower HE in the MARS

group compared with SMT group

Heemann U et al. Hepatology. 2002 Oct;36(4 Pt 1):949-58.

11 12
 Randomized controlled study of extracorporeal albumin dialysis for hepatic
encephalopathy in advanced cirrhosis
30-day-survival
(Kaplan-Meier-plot)

1
SMT + MARS
0,8
p<0.05
Cumulative survival

0,6
SMT
0,4

0,2

0
0 10 20 30
Hospital days

Heemann et al., Hepatology 2002;36:949-958 Hassanein TI, et al. Hepatology. 2007 Nov 1

Mean cumulative number of

improvements per person in MARS
versus SMT. By 120 hours, the
MARS group mean is almost twice
the SMT mean
Kaplan-Meier estimated time to first
improvement in MARS versus SMT.
Patients in the MARS group
responded faster and at a higher rate
than patients in the SMT group (Log-
rank test P = 0.045).
Hassanein TI, et al. Hepatology. 2007 Nov 1
Hepatorenal syndrome
• Type one hepatorenal syndrome is a complication of both
acute and chronic hepatic failure with an excessive
mortality of more than 80% in two weeks
• Vasopressin analogue or hemodiafiltration had not been
shown to improve survival in HRS
• TIPs has been shown to improve survival in HRS but poor
results were noted in patients with high bilirubin levels
• The use of MARS has been associated with a significant
improvement in survival compared with the
hemodiafiltration group
Mitzner et al. Liver Transpl. 2000 May;6(3):277-86.
16
 Impact on survival

Patients with HRS type I

Hypoglycemia
(TIPSS contra-indicated)
• Glucose is constantly removed from the MARS
1 system during dialysis. Mean glucose removal during
a 6-hour MARS session was 37.19 +/- 5.58 g. at a
0,8
p < 0.02 rate of 6.20 +/- 0.93 g/h.
Cumulative

0,6
• Close monitoring of blood glucose and dextrose
survival

0,4 infusion during MARS may be necessary to avoid

SMT +
0,2 MARS®
hypoglycemia.

0
SMT Khoo et al. Liver Transpl. 2003 Sep;9(9):949-53 .
0 10 20 30
Hospital
days

Mitzner et al., Liver Transplantation 2000;6(3)

18

Other complications
• MARS is a form of
dialysis and all
potential
complications with
hemodialysis and
hemofiltration can
occur with MARS

.
Khoo et al. Liver Transpl. 2003 Sep;9(9):949-53

19 20
 Extracorporeal elimination of ceftriaxone ( highly protein
bound)
Drug administration
• Protein bound drugs needs to be
readministered after MARS because of
significant removal by the treatment
• Alternatively continuous infusion and
concentration assays may be necessary

Majcher Peszynska et al . Z Gastroenterol. Supp (2001) 39: 33-35

21 22

Extracorporeal elimination of ceftazidime ( non protein

bound)

Majcher Peszynska et al . Z Gastroenterol. Supp (2001) 39: 33-35

23 24
 Economic and financial concerns Nursing concerns

Hessel FP
Economic evaluation of the artificial liver support system MARS in
patients with acute-on-chronic liver failure
Cost Eff Resour Alloc. 2006 Oct 5;4:16.

Case 1 Case 1 Creatinine, umol/L

Bilirubin, umol/L
Platelet, x 10^9/L
MARS
↓
• F / 25 Nepali, imported domestic helper
• Non smoker non drinker
• Acute liver failure, unknown cause, probably related to
use of herbal medication
• Developed hepatorenal syndrome
• Transferred to transplant centre for consideration of
orthotopic liver transplantation

days
 Case 2 Case 2
Bilirubin umol/L Creatinine umol/L

MARS
• M/55 HBV Child C cirrhosis
↓ MARS
• Acute on chronic liver failure predisposed by pneumonia MARS ↓
↓ OLTx
• Developed to hepatic encephalopathy and hepatorenal ↓

syndrome
• No family members were appropriate candidates for living
related donor liver transplantation

AoCLF with MARS: failed to bridge to Case 3

liver transplantation
Bilirubin umol/L Creatinine umol/L
• M/41 non smoker non drinker
• Child C cryptogenic liver cirrhosis
• Received living related liver transplantation
• Initially stable in early post operative period but
developed sepsis and required 2 times explorative
laparotomy
• Graft function deteriorated and developed
progressive renal failure as well.
days
 Case 3 Creatinine, umol/L
When should MARS be started
Bilirubin, umol/L

OLTx MARS • Based on biochemical abnormality?

↓ ↓
• Based on clinical syndrome?
• Last resort for liver failure?
• Tool to prevent deterioration?
• Priming treatment before liver transplantation

Initiation of MARS Criteria for performing MARS at

• Initiation of MARS should not be based on an
absolute level of biochemical abnormality as this
may varies widely among different patients
• On the other hand, the velocity of deterioration is
more important
• Communication with the referring team is important
• Benefit of MARS decline as patient gets more sick
• A tool to prevent deterioration but not to salvage
devastation
QMH
• Potential liver transplantation candidate
• Deteriorating biochemistry
• Clinical manifestation of liver failure
• No immediate life donor for living related
transplantation ( exception: MARS priming )
• Able to sustain extracoporeal circuitry
• Secondary dominant pathology under control: severe
sepsis, acute myocardial infraction, gastrointestinal
bleeding
Thank you