it is unlikely that one solution will work……... what are the aims of a liver support device?...
TRANSCRIPT
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It is unlikely that one solution will work……..
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What are the aims of a liver support device?
• Decompensated cirrhosis• Prevention of further deterioration (ie) AoCLD• Stability on the transplant list : decreased infections, portal pressure and variceal bleeding, control of ascites
• Acute on chronic liver disease• Reversal of type I HRS, stabilization type II HRS• Reversal of hepatic encephalopathy• Improved synthetic function / nutritional status•Control pruritis
• Critically ill cirrhotic
• Reversal of organ failure - ability to transplant
• Acute liver failure
• Control ICP
• Avoidance transplantation / Regeneration or stability to transplant
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Biochemical Effects: Co-founders?
Kramer et al Int J Artif Org 2002;25:918-22AOCLF n=8
Effect of IV Colloid on bilirubin level prior to liver supportBilirubin measured; baseline, post colloid (10 ml/kg 6% HAES solution)
Bilirubin Fall p
Baseline to post-colloid 18% (1-44) <0.03
Conjugated Bilirubin decreases only – water soluble
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Relationship of Bilirubin to serum albumin in 11 patients with MOF and liver failure
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5 Gambro standard presentation November 1© 2011, Gambro
Albumin Dialysis : membrane 50 KD pore size
MARS® vs. Renal Replacement
Blood Circuit
Dialysate Circuit
Albumin Circuit
Courtesy: Gambro (Josep Torner)
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Number of improved assessments : study 5 days Responder : 1 or more episode of 2 grade improvement70 enrolled GCS 6/15Sedation undertaken in 10 and 13%Platelets decreased 21% - Rx needed in 49 and 32%5 episodes of stopping Rx During follow -up 7 episodes GI bleeding MARS vs 1 in SMT
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2-grade improvement in HE34% in MARS group19% in SMT group (p=0.044)
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Variable SMT SMT+MARS PHRS (n (%)) 45 (52.9 %) 37 (52.1 %) NSEncephalopathy ≥ grade II (n (%))
37 (43.5 %) 28 (39.4 %) NS
SOFA score (n=95) 7.7 (3.3) 8.1 (2.8) NSGCS (n=140) 13 (3) 13 (4) NSBilirubin (mg/dl) 27.0 (12.3) 26.8 (11.8) NSAlbumin (g/L) 28.1 (9.9) 27.3 (6.3) NSSerum creatinine 2.27 (2.07) 2.50 (2.20) NSINR 1.78 (0.33) 1.74 (0.31) NSHematocrit 29.3 (6.0) 28.4 (4.8) NSLeucocytes 15.6 (11.0) 16 (9.6) NSPlatelet count 120.3 (72.3) 130.9 (75.2) NS
MELD > 20 (n(%)) 59 (69.4 %) 58 (81.7 %) P=0.078SBP (n (%)) 6 (7.1 %) 12 (16.9 %) P=0.055
Table 1: Baseline characteristics (per protocol)
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SMT +MARSSMT
302520151050
1.0
0.8
0.6
0.4
0.2
0.0
Overall 28 days mortality: SMT: 39.3 % SMT + MARS: 41.4 %
Overall 28 days mortality: SMT: 40 % SMT + MARS: 41.2 %
302520151050
1.0
0.8
0.6
0.4
0.2
0.0
SMT +MARSSMT
ITT population PP population
10Confidential
Log-rank test: p=0.79 Log-rank test: p=0.88
• reduces toxins• improves hepatic coma• improves hemodynamic instability
RELIEF (MARS) study n=185Fall in creatinine (p=0.02) and bilirubin (p=0.01)Improvement in HE from II/IV at inclusion to 0-I, 56 vs 39%28 day survival 40 vs 40.8%
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HELIOS study
Objective:
· To test survival under Prometheus therapy with standard medical therapy (SMT) compared to SMT alone
Patients:
· Acute decompensation of chronic liver disease
· Presence within last 72 hours of - CP-Score 10 - Bilirubin 5 mg/dl
· Exclusion: 16 major comorbidities
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Effect of PROMETHEUS on survival
Day 28 SMT+FPSA: 66%SMT: 63% Diff. ~ 3 %, NS Day 90
SMT+FPSA : 47%SMT: 38% Diff. ~ 9%, NS
Day 21Diff.~10%
reduces toxinseffective in certain sub-groups
GASTROENTEROLOGY 2012;142:782–789
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LIVER TRANSPLANTATION 21:369–380, 2015
Willem S. Lexmond,
Case series : no difference in MARS vs non- MARS treated patients
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Pierre Bourgoin Pediatr Nephrol (2014) 29:901–908
Haemodynamics unstable in mini mars Rx (0.6 m2 – prime volume 172 vs 2.1 and 275 ml)Cut point 25 kg
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Nephrol Dial Transplant (2011) 26: 3633–3639
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Superior efficay of PE / HD vs MARS in ALF cases
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Wai et al 2006
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FULMAR (Saliba et al)
• Prospective, controlled, randomized parallel group trial – Total number of patients: 102 (ITT)– Main etiology of ALF due to Acetaminophen (38%)
• SMT = 19, MARS=20
• Comparison of SMT versus SMT + MARS Indication • ALF, with indication for liver transplantation • 68/102 patients transplanted
– 41% of acetaminophen group
Ann Intern Med. 2013;159:522-531.
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Median 16 hours from wait list to TxMedian number Rx 1 (0-7)
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Ann Intern Med. 2013;159:522-531.
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Sauer et al Hepatology 2004;39:1048
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Can J Gastroenterol Vol 26 No 11 November 2012
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Risks vs benefits
• All studies have appeared safe • Antimicrobial clearance • Coagulation
– How to anticoaguate the circuit – Improved coagulation
• System functioning
– Deteriorating coagulation – Fall in fibrinogen, platelets
• Intravascular haemolysis
Doria et al Clinical Transplantation 2004;18:365
SPAD and Wilsons
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Journal of Hepatology 2015 Jalan et al
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Didier M. Payen
Intensive Care Med April 2015
Abdominal peritonitis Lower (82),upper (32) and biliary (6)X 2 treatments post surgery10 &24 hrs) Annonymized assessment of surgery
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Transplant International ISSN 2007