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Adrian Gadano - Argentina - Tuesday 29 - Liver Transplantation Towards New Horizons
1. Bridging Devices to Transplant: Is there need to establish a distribution criteria ? Hospital Italiano de Buenos Aires Unidad de Hígado y Trasplante Hepático Adrián Gadano, MD Sección de Hepatología Hospital Italiano de Buenos Aires Fundación Icalma
2. Acute Liver failure Liver function and histology are normal 2-8 weeks before the onset Liver Failure: Two different Scenarios…
3. “ A devastating condition, potentially reversible , which is a consequence of massive hepatic necrosis and is characterized by the presence of hepatic encephalopathy within the first 12 (24) weeks after the onset of symptoms “ Durand y Bernuau, 2006 Acute Liver Failure
4. Acute Liver failure Acute on Chronic Liver Failure Liver function and histology are normal 2-8 weeks before the onset Pre-existing damaged liver Liver Failure: Two different Scenarios…
13. “” liver transplantation cannot be accepted as the perfect and ideal treatment for fulminant hepatic failure” S Sherlock Liver Transplantation: - Procedure risk - Overindication - Life-long immunosuppression Liver transplantation in ALF
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15. Acute Liver Failure Indication for Transplantation < 20% recovery and survival > 80% bad outcome and dead OLT emergency King’s and Clichy criteria
16. Time on the waiting list for OLT in patientes with ALF: Hospital Italiano - 2010
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18. 20 % Outcome after inclusion on the waiting list Hospital Italiano: outcome of 119 ALF patients listed for transplantation
26. Bio-artificial liver support * Except in a subgroup System origin hepatocytes blood/ plasma Controlled study Survival benefit ELAD USA human blood yes no HepatAssist USA porcine plasma yes no* TECA-HALSS China porcine plasma no - BLSS USA porcine blood no - RFB Italy porcine plasma no - LSS/MELS Germany porcine/human plasma no - AMC-BAL Holland porcine plasma no - HBAL China porcine plasma no -
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28. IT TAKES A VILLAGE TO BUILD A LIVER BLOOD In Flow Nutrients Nature Biotech 2005;23:1237-9 Scaffold Proteins Stem cells Hedgehog Notch Wnt Signaling Factors
33. Albumin dialysis diaMARS ® AC250 adsorber (Adsorbente de carbón activado) diaMARS ® IE250 adsorber (intercambiador de aniones) Non Biologic Liver Support MARS (Molecular Adsorbents Recirculating System)
41. MARS ® in patients with acute liver failure MARS Control p Change in ICP (mmHg) ? ? ? Change in CPP (mmHg) ? ? ? Waiting list mortality ? ? ? Survival after transplantation ? ? ?
50. P. Krisper et al. / Journal of Hepatology 43 (2005) 451–457
51. Prometheus vs. Mars -0,10 0, 00 0,10 0,20 0,30 0,40 0,50 0,60 0,70 Urea Reduction Ratios (RR) p < 0.01 9 Patients MARS vs. 9 Patients Prometheus p < 0.05 Total Bilirubin Bile Acids Creatinin Evenepoel P, 2005 p < 0.05 * = not significant * MARS Prometheus
52. 0 5 10 15 20 25 30 35 40 1. Treatm. Total Bilirubin concentration (mg/dl) pre treatment post treatment Treatment duration 6.5 h Mo Tu 2. Treatm. We Th 3. Treatm. Fr Sa So Mo Tu 4. Treatm. We by courtesy of S. Herget-Rosenthal, U. Treichel, F. Saner, F. Pietruck, C. Broelsch, G. Gerken, T. Philipp, A. Kribben - 2006 Decrease of Bilirubin with Prometheus® OLT
53. Case report Nephrology dep. Univ. Frankfurt, Aug. 2004: 38 y, male, end stage liver failure with ascites, HE II-III, Child C, HRS, T2 listed 23 treatments, average 4.5 h, every 2nd day for 51 days By courtesy C.Betz, Frankfurt - 2006 Puente al Trasplante Disminución de la Bilirubina con Prometheus® 0 5 10 15 20 25 30 35 40 45 50 55 0 5 10 15 20 25 30 35 (days) (mg/dl) LTX total serum bilirubin
54. Treatment of Refractory Pruritus with Prometheus Rifai K, Scand J Gastroenterol. 2006 Oct;41(10):1212-7. OLT 3 - 5 Treatments
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56. Apart from invaluable increase of survival rate, the application of Prometheus therapy led to a considerable economic relief of public health care costs. In comparison to the saved costs of 900,000 € for nine avoided liver transplantations including follow-up costs in the first year (regardless costs and consequences of immunosuppression for the rest of live) the expenditure of about 200,000 € for 85 performed Prometheus treatments seems to make good economic sense. In other words, cost saving is about 700,000 €. Seen from this point of view the Prometheus therapy is quite an economically meaningful therapy option in liver failure.
60. HELIOS Study Promet h eus E uropean L iver D i sease O utcome S tudy Aim: Demonstration of clinical benefits of Prometheus ® therapy for patients with acute-on-chronic liver failure ( AOCLF) Hospitals: 10 university hospitals from 7 european countries (e.g.: Univ. Frankfurt, Hannover, Barcelona, London) Patients: 145 patients; AOCLF ( bilirubin ≥ 5 mg/dl and Child Pugh Score ≥ 10) Analysis: All Patients Subgroups: - Patients with HRS Typ 1 - Patients with MELD Score > 30 Rifai et al, AASLD 2010
61. HELIOS Study: - Decompensated cirrhosis - Age 51+30 - Etiology: Alcohol 56%, Hepatitis 20% - MELD 27+10 - Survival at 28 and 90 days SMT (n=68) vs SMT+Prometheus (n=77) acute-on-chronic liver failure (AOC) EXTRACORPOREAL LIVER SUPPORT BY FRACTIONATED PLASMA SEPARATION AND ADSORPTION (PROMETHEUS®) IN PATIENTS WITH ACUTE-ON CHRONIC LIVER FAILURE (HELIOS STUDY): A PROSPECTIVE RANDOMIZED CONTROLLED MULTICENTER STUDY Rifai et al, AASLD 2010
62. Promet h eus E uropean L iver D i sease O utcome S tudy Study Design HELIOS Study 1. Screening phase 3 days Randomisation 1:1 2. Treatment phase 21 days 3. Follow up phase 69 days SMT SMT + FPSA (8 11x) d 21 d 0 d 28 d 7 d 14 Study visits : : SMT d 90 69 days : :
63. Day 28 Diff. ~ 23%; NS Day 90 Diff. ~ 36%; p < 0,05 Prometheus + SMT SMT Subgroup: HRS Type 1 Days Survival Probability / % Probability of survival was 36% higher in “Prometheus group” at day 90 (p=0,02) HELIOS Study Results Rifai et al, AASLD 2010
64. Subgroup: MELD Score > 30 Probability of survival was 39% higher in “Prometheus group” at day 90 (p=0.04) Day 28 Diff. ~ 15%; NS Day 90 Diff. ~ 39%; p < 0,05 Prometheus + SMT SMT Days Survival Probability / % HELIOS Study Results Rifai et al, AASLD 2010
65. Prometheus aumenta la sobrevida en AOC: - MELD score >30 (p=0.02) - Sindrome Hepatorenal tipo I (p=0.04) EXTRACORPOREAL LIVER SUPPORT BY FRACTIONATED PLASMA SEPARATION AND ADSORPTION (PROMETHEUS®) IN PATIENTS WITH ACUTE-ON CHRONIC LIVER FAILURE (HELIOS STUDY): A PROSPECTIVE RANDOMIZED CONTROLLED MULTICENTER STUDY Rifai et al, AASLD 2010 AOC MELD score >30 P<0.02 P<0.02
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67. Positive prognostic value, negative prognostic value and diagnostic accuracy of the MELD score in detecting patients with acetaminophen and non-acetaminophen-induced ALF MELD > 30 in 94% of pts who died without OLT MELD < 30 in 91% of pts who survived with medical support Wei, HPDI 2010 Yantorno, Liver Transpl 2007
Un peu chargé. Tu aurais pu faire 2 diapos distinctes.
Un peu chargé. Tu aurais pu faire 2 diapos distinctes.
Es por eso que las infecciones bacterianas son mas frecuentes en pacientes con enfremedad más avanzada
J’ajouterais quelque part les notions de « remplacement des fonctions de synthèse » du côté foie bioartificiel et « remplacement des fonctions d’épuration » du côté épuration extra hépatique.
Un peu chargé. Tu aurais pu faire 2 diapos distinctes.
Avec la diapo précédente, on peut illustrer le principe de l’interposition d’un circuit de dialyse à l’albumine.
