Steffen Mitzner 54th ASAIO Conference San Francisco June 21, 2008 University of Rostock Germany Albumin Dialysis  MARS:  I...
International MARS Registry
MARS- Randomized clinical trials INDICATION n INCLUSION STATUS REMARK Chirr w HRS 13 AoCLF, HRS Type I  need for RRT Compl...
MARS- Reduction of Albumin bound Toxins Liver Transplantation, Vol 6, 2000: 603-613 P<0,0001 P<0,0001 normal Serum Bile Ac...
Albumin Dialysis MARS- Clinical effects Summary <ul><li>Cardiovascular system (SVRI   , MAP   )   </li></ul>  University...
<ul><li>Liver failure with Hyperdynamic Hypotension </li></ul>Indications for Liver support therapy
MARS in Hyperacute ALF   SVRI  MAP Schmidt et al., Liver Transplantation 2003;9:290-297 Hypothermia MARS p = 0.004 p < 0.0...
  Cardiac index   Heart rate Schmidt et al., Liver Transplantation 2003;9:290-297 MARS in Hyperacute ALF p = 0.0007 p = 0....
Heemann U. et al Hepatology 2002; 36: 949-58 MARS in Acute Decompensation of Chronic Liver Failure Prospective randomized ...
Liver support: Effect on mean arterial pressure SMT MARS PROMETHEUS P  = 0.050 P  = 0.014 P  = 0.844 Laleman W et al. Crit...
Liver support: Effect on systemic vascular resistance index SMT MARS PROMETHEUS P  = 0.389 P  = 0.036 P  = 0.120 Laleman W...
Liver support: Changes in endogenous vasoactive substances: Effect on nitric oxide * * P  < 0.001 vs SMT and PROM P =0.016...
MARS: Impact on Portal Pressure MARS Jalan R. et al., J Hepatol. 2005
<ul><li>Liver failure with increased </li></ul><ul><li>Intracranial Pressure (ICP) </li></ul>Indications for Liver support...
 
MARS: Impact on Intracranial Pressure Sen S. et al., Crit. Care Med. 2006 Pig model of ALF
<ul><li>Liver failure with Renal Insufficiency </li></ul><ul><li>Hepatorenal Syndrome </li></ul>Indications for Liver supp...
MARS in HRS Type I:  MAP and Urine volume Mitzner et al. Liver Transplantation 2000; 6: 277-86
Heemann et al.: Hepatology 2002;36:949-958 MARS in AoCHF:  Impact on renal function SMT group (n=11) MARS group (n=12) P-v...
<ul><li>Liver failure with </li></ul><ul><li>Hepatic Encephalopathy </li></ul>Indications for Liver support therapy
MARS in End Stage Liver Disease and Advanced HE: Prospective, controlled, randomized multi- center trial Baseline data / R...
Primary Endpoint (ITT) MARS SMT p = 0.044 n = 70 Hassanein T et al. Hepatology 2007; 46: 1853-62
<ul><li>Supportive Therapy prior to Liver Transplantation </li></ul>Indications for Liver support therapy
MARS before Liver Transplantation Koivusalo AM et al. Transpl Proceed 2005;37:3315-17 56 patients with ALF (29 toxic, 22 u...
<ul><li>Improvement of Survival </li></ul>Indications for Liver support therapy
Kjaergard LL et al. JAMA 2003; 289:217-222 Cochrane Hepato-Biliary Group: Systematic Review … support systems appeared to ...
MARS in Hepatorenal Syndrome  Survivalrates Mitzner S et al. Liver Transplantation 2000; 6: 277-86
Survival rates MARS  (n=12) Control  (n=12) Survival Days p<0,05 Hepatology 2002;  36: 949- 58 MARS in Acute Decompensatio...
Conclusions <ul><li>MARS is in clinical use since 1998. It is the best studied liver </li></ul><ul><li>support system at p...
WELCOME to the ISAD 2008 September 12-14, 2008 Rostock, Germany www.albumin-dialysis.org
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Steffen Mitzner 54th ASAIO Conference

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  • Hemodynamic measurement in the different groups showed a worsening of systemic arterial pressure in the smt group, whereas this significantly improved after mars treatment and stabilized in the prometheus group
  • Similar findings occurred when comparing the svri, only in the mars group there was a significant increase in svri. CVP, CI and HR did not change significantly during the study period.
  • Interestingly enough, the hemodynamic improvement in the MARS group was accompagnied by a decrease in endogenous circulating vasoactive substances. Both NO, a key molecule in the hyperdynamic state, as vasoconstrictor substances such as pra and aldo were significantly decreased as compared to smt and prom
  • Steffen Mitzner 54th ASAIO Conference

    1. 1. Steffen Mitzner 54th ASAIO Conference San Francisco June 21, 2008 University of Rostock Germany Albumin Dialysis MARS: Indications and Clinical Results
    2. 2. International MARS Registry
    3. 3. MARS- Randomized clinical trials INDICATION n INCLUSION STATUS REMARK Chirr w HRS 13 AoCLF, HRS Type I need for RRT Completed Liver Transpl 2000 AoCLF 24 AoCLF, Bili > 20mg/dL Completed Hepatology 2002 ALF 13 HyperALF; HE III/IV Completed Liver Transpl 2003 AoCLF in alcoholic liver disease 16 AoCLF, Bili>15mg/dL, HE  II°, HRS Completed Liver Transpl 2004 Hypoxic liver failure post LOF 40 Hypoxic LF, Bili > 8mg/dL Completed ASAIO J 2004 Chirr w HE 70 AoCHF, HE III/IV FDA controlled Completed Hepatology 2007 ALF (FULMAR-trial) 120 ALF (French criteria) EnrolementCompleted AoCLF with hyperbili + HE/HRS (MARS-RELIEF) 230 AoCLF, Bili > 5mg/dL + HE  II° or HRS Ongoing
    4. 4. MARS- Reduction of Albumin bound Toxins Liver Transplantation, Vol 6, 2000: 603-613 P<0,0001 P<0,0001 normal Serum Bile Acids Serum Bilirubin umol/l Start Start End End Serum Bilirubin Start End Hours umol/l Serum Bile Acids Start umol/l Hours
    5. 5. Albumin Dialysis MARS- Clinical effects Summary <ul><li>Cardiovascular system (SVRI  , MAP  ) </li></ul> University of Rostock, 2008 <ul><li>QOL (pruritus  , fatigue  ) </li></ul><ul><li>Liver function (PDR ICG  , others) </li></ul><ul><li>Kidney function (Urine output  , Creat.  ) </li></ul><ul><li>Cerebral function (HE  , ICP  ) </li></ul><ul><li>Organ perfusion  (brain, kidney) </li></ul><ul><li>Portal pressure  </li></ul>
    6. 6. <ul><li>Liver failure with Hyperdynamic Hypotension </li></ul>Indications for Liver support therapy
    7. 7. MARS in Hyperacute ALF SVRI MAP Schmidt et al., Liver Transplantation 2003;9:290-297 Hypothermia MARS p = 0.004 p < 0.0001 p < 0.0001 N.S.
    8. 8. Cardiac index Heart rate Schmidt et al., Liver Transplantation 2003;9:290-297 MARS in Hyperacute ALF p = 0.0007 p = 0.03 p < 0.0001 N.S. Hypothermia MARS
    9. 9. Heemann U. et al Hepatology 2002; 36: 949-58 MARS in Acute Decompensation of Chronic Liver Failure Prospective randomized two- center trial Time MARS was administred
    10. 10. Liver support: Effect on mean arterial pressure SMT MARS PROMETHEUS P = 0.050 P = 0.014 P = 0.844 Laleman W et al. Crit Care 2006;10:R108
    11. 11. Liver support: Effect on systemic vascular resistance index SMT MARS PROMETHEUS P = 0.389 P = 0.036 P = 0.120 Laleman W et al. Crit Care 2006;10:R108
    12. 12. Liver support: Changes in endogenous vasoactive substances: Effect on nitric oxide * * P < 0.001 vs SMT and PROM P =0.016 Delta SVRI (dyne.s.cm-5.m-2) Delta NOx (nM) Laleman W et al. Crit Care 2006;10:R108 *
    13. 13. MARS: Impact on Portal Pressure MARS Jalan R. et al., J Hepatol. 2005
    14. 14. <ul><li>Liver failure with increased </li></ul><ul><li>Intracranial Pressure (ICP) </li></ul>Indications for Liver support therapy
    15. 16. MARS: Impact on Intracranial Pressure Sen S. et al., Crit. Care Med. 2006 Pig model of ALF
    16. 17. <ul><li>Liver failure with Renal Insufficiency </li></ul><ul><li>Hepatorenal Syndrome </li></ul>Indications for Liver support therapy
    17. 18. MARS in HRS Type I: MAP and Urine volume Mitzner et al. Liver Transplantation 2000; 6: 277-86
    18. 19. Heemann et al.: Hepatology 2002;36:949-958 MARS in AoCHF: Impact on renal function SMT group (n=11) MARS group (n=12) P-value In-hospital deaths 6 1 < 0.05 Worsening of hepatic encephalopathy (° IV) 3 0 < 0.05 Severe hypotension 2 3 NS Worsening of renal function (HRS) 7 1 < 0.05 Developing electrolyte disorders 10 4 < 0.05 New formation of ascites 1 0 NS Coagulopathy 3 4 NS Variceal bleed 1 0 NS
    19. 20. <ul><li>Liver failure with </li></ul><ul><li>Hepatic Encephalopathy </li></ul>Indications for Liver support therapy
    20. 21. 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 % Hassanein T et al. Hepatology 2007; 46: 1853-62 <ul><li>- ITT analysis: SMT (n=31) vs. MARS (n=39) 38 vs. 62% (p=0.04) </li></ul><ul><li>PP analysis: SMT (n=29) vs. MARS (n=33) 38 vs. 70% (p=0.007) </li></ul><ul><li>MARS group had signif. improvement in serum ammonia, total bilirubin, </li></ul><ul><li>bile acids, creatinine, and aromatic acids </li></ul>
    21. 22. Primary Endpoint (ITT) MARS SMT p = 0.044 n = 70 Hassanein T et al. Hepatology 2007; 46: 1853-62
    22. 23. <ul><li>Supportive Therapy prior to Liver Transplantation </li></ul>Indications for Liver support therapy
    23. 24. MARS before Liver Transplantation Koivusalo AM et al. Transpl Proceed 2005;37:3315-17 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%)
    24. 25. <ul><li>Improvement of Survival </li></ul>Indications for Liver support therapy
    25. 26. Kjaergard LL et al. JAMA 2003; 289:217-222 Cochrane Hepato-Biliary Group: Systematic Review … support systems appeared to reduce mortality by 33% in ACLF (RR 0,67; 95% CI 0,51-0,90)
    26. 27. MARS in Hepatorenal Syndrome Survivalrates Mitzner S et al. Liver Transplantation 2000; 6: 277-86
    27. 28. Survival rates MARS (n=12) Control (n=12) Survival Days p<0,05 Hepatology 2002; 36: 949- 58 MARS in Acute Decompensation of chronic liver failure Prospective randomized two- center trial
    28. 29. Conclusions <ul><li>MARS is in clinical use since 1998. It is the best studied liver </li></ul><ul><li>support system at present time. </li></ul><ul><li>Indications treated include ACLF, ALF, PNF, postop. LF, HRS, </li></ul><ul><li>pruritus and others in adults and pediatric cases. </li></ul><ul><li>The system successfully removes albumin-bound as well as </li></ul><ul><li>water-soluble substances. </li></ul><ul><li>Clinical effects include improvement of hemodynamic, cerebral, </li></ul><ul><li>kidney, and liver function. </li></ul><ul><li>Increased survival in the MARS-group could be demonstrated in </li></ul><ul><li>several RCTs. </li></ul><ul><li>Patient selection should be strict. Early onset of treatment ensures </li></ul><ul><li>best clinical results at reasonable costs. </li></ul>
    29. 30. WELCOME to the ISAD 2008 September 12-14, 2008 Rostock, Germany www.albumin-dialysis.org
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