Steffen Mitzner

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54th ASAIO Conference San Francisco June 21, 2008
Albumin Dialysis MARS Indications and Clinical
Results

• Steffen Mitzner

University of Rostock Germany
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International MARS Registry
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MARS- Randomized clinical trials
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MARS- Reduction of Albumin bound Toxins
Serum Bile Acids
Serum Bilirubin
umol/l
Plt0,0001
Plt0,0001
normal
Start
Start
End
End
Liver Transplantation, Vol 6, 2000 603-613
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Albumin Dialysis MARS- Clinical effects Summary

• Cardiovascular system (SVRI ?, MAP ?)

• Portal pressure ?

• Organ perfusion ? (brain, kidney)

• Cerebral function (HE?, ICP?)

• Kidney function (Urine output ?, Creat. ?)

• Liver function (PDR ICG ?, others)

• QOL (pruritus ?, fatigue ?)

University of Rostock, 2008
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Indications for Liver support therapy

• Liver failure with Hyperdynamic Hypotension

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MARS in Hyperacute ALF
SVRI MAP
Schmidt et al., Liver Transplantation
20039290-297
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MARS in Hyperacute ALF
Cardiac index Heart rate
Schmidt et al., Liver Transplantation
20039290-297
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MARS in Acute Decompensation of Chronic Liver
Failure Prospective randomized two- center trial
Heemann U. et al Hepatology 2002 36 949-58
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Liver support Effect on mean arterial pressure
SMT
MARS
P 0.050
P 0.014
PROMETHEUS
P 0.844
Laleman W et al. Crit Care 200610R108
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Liver support Effect on systemic vascular
resistance index
SMT
MARS
P 0.389
P 0.036
PROMETHEUS
P 0.120
Laleman W et al. Crit Care 200610R108
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Liver support Changes in endogenous vasoactive
substances Effect on nitric oxide
Delta SVRI (dyne.s.cm-5.m-2)
P0.016
Delta NOx (nM)


P lt 0.001 vs SMT and PROM
Laleman W et al. Crit Care 200610R108
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MARS Impact on Portal Pressure
MARS
Jalan R. et al., J Hepatol. 2005
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Indications for Liver support therapy

• Liver failure with increased
• Intracranial Pressure (ICP)

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(No Transcript)
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MARS Impact on Intracranial Pressure
Pig model of ALF
Sen S. et al., Crit. Care Med. 2006
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Indications for Liver support therapy

• Liver failure with Renal Insufficiency
• Hepatorenal Syndrome

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MARS in HRS Type I MAP and Urine volume
Mitzner et al. Liver Transplantation 2000 6
277-86
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MARS in AoCHF Impact on renal function
Heemann et al. Hepatology 200236949-958
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Indications for Liver support therapy

• Liver failure with
• Hepatic Encephalopathy

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MARS in End Stage Liver Disease and Advanced
HE Prospective, controlled, randomized multi-
center trial
Baseline data / Results - 70 pat. in 8 centers
(6 USA and 2 European) - Age 52.7 10.9, 44
female MELD 31 10, CTP 12.7 1.3, HE grade
III 56, HE grade IV 44 - HE-assessment every 12
hours for 5 days (10 per pat.) -Responder
2-grade-improvement - primary endpoint
Improvement proportion

• - ITT analysis SMT (n31) vs. MARS (n39) 38 vs.
  62 (p0.04)
• PP analysis SMT (n29) vs. MARS (n33) 38 vs.
  70 (p0.007)
• MARS group had signif. improvement in serum
  ammonia, total bilirubin,
• bile acids, creatinine, and aromatic acids

Hassanein T et al. Hepatology 2007 46 1853-62
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Primary Endpoint (ITT)
n 70
MARS
p 0.044
SMT
Hassanein T et al. Hepatology 2007 46 1853-62
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Indications for Liver support therapy

• Supportive Therapy prior to Liver Transplantation

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MARS before Liver Transplantation
56 patients with ALF (29 toxic, 22 unknown, 5
other) All pats. fullfilled TX criteria or had
ingested a lethal dose of a known toxic agent
(e.g. paracetamol, Amanita phalloides) Mean
number of 3 Rx per pat., target duration
22h/session
6 month survival 88, 1 year survival
84 Recovery of native function in 30 pats (1y
survival 79) Successful LTx in 17 pats (1 y
survival 94)
Koivusalo AM et al. Transpl Proceed
2005373315-17
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Indications for Liver support therapy

• Improvement of Survival

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Cochrane Hepato-Biliary Group Systematic Review
Kjaergard LL et al. JAMA 2003 289217-222
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MARS in Hepatorenal Syndrome Survivalrates
Mitzner S et al. Liver Transplantation 2000 6
277-86
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MARS in Acute Decompensation of chronic liver
failure Prospective randomized two- center trial
Survival rates
Survival
MARS (n12)
Control (n12)
plt0,05
Days
Hepatology 2002 36 949- 58
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Conclusions

• MARS is in clinical use since 1998. It is the
  best studied liver
• support system at present time.

• Indications treated include ACLF, ALF, PNF,
  postop. LF, HRS,
• pruritus and others in adults and pediatric
  cases.

• The system successfully removes albumin-bound as
  well as
• water-soluble substances.

• Clinical effects include improvement of
  hemodynamic, cerebral,
• kidney, and liver function.

• Increased survival in the MARS-group could be
  demonstrated in
• several RCTs.

• Patient selection should be strict. Early onset
  of treatment ensures
• best clinical results at reasonable costs.

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WELCOME to the ISAD 2008 September 12-14,
2008 Rostock, Germany www.albumin-dialysis.org