Perspectives in Liver Transplantation

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Artificial Liver Support

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This book is the proceedings of the Falk Symposium No. 145 on ‘Artificial Liver Support’, held on 27--28 January 2005 in Ulm, Germany, and provides an overview of the possibilities and limitations of the existing procedures and devices available for artificial liver support. The book is written for clinicians, researchers, graduate students, and academics.
For more than 25 years clinicians and scientists have been trying to improve the treatment of acute hepatic failure. Several devices were developed and hemodialysis procedures were refined. The treatment of fulminant hepatic failure and end-stage liver cirrhosis by liver transplantation became a standard procedure. However, for the successful management of critical situations before and after liver surgery, artificial liver support is still needed. The results achieved with albumin dialysis (MARS System), the Prometheus System, and dialysis and hemofiltration or plasma exchange as well as modular extracorporeal liver support (MELS) and the Amsterdam bioartificial liver (AMC BAL) are discussed in detail regarding their effects in different clinical situations.
In the second half of the book, the remaining problems and expectations for the future of clinical hepatocyte transplantation and stem cell therapy are elucidated.
Leading experts in the fields of artificial devices, bioartificial devices, hepatocyte transplantation and stem cells present the latest data on these topics. Their experience and their data are summarized in this volume, thus providing an exceptional overview of the problems and future perspectives in the field of artificial liver support.
Artificial Liver Support Series: Falk Symposium, Vol. 145 Henne-Bruns, D.; Buttenschön, K.; Fuchs, M.; Lohse, A. (Eds.) Springer-Verlag 2005 (ISBN: 1-4020-3239-0)

The European artificial organ scene: present status

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This article by R. Vanholder, J.F. Del Canizo, I.M. Sauer, and B. Stegmayr summarizes the current evolutions regarding artificial organs in Europe. The review emanates from the activities by four of the work groups of the European Society for Artificial Organs (ESAO) and is essentially based on the reports by these work groups at the latest ESAO meeting in Warsaw, Poland (2004). The topics are: apheresis, heart support, liver support, uremic toxins. Artif Organs. 2005 Jun;29(6):498-506.

3rd Int. Symp. on Hepatic failure and Artificial Liver

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The Third International Symposium on Hepatic failure and Artificial Liver will be held from Mar 24-27, 2005 in Suzhou, China. The sponsors include Chinese Medical Association Zhejiang Branch and First Affiliated Hospital, Medical College, Zhejiang University. This symposium is aimed to promote the international communication, further the study on artificial liver, popularize the usage of artificial liver system. The conference is focussing on “Developing Artificial Liver, Curing Hepatic Diseases”.

Artificial Organs and Organ Transplantation

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The Institute of Biomedical engineering, Materials Science and Application (BMSA), and the Department of Surgery (GUMC) organise the symposium: Artificial Organs and Organ Transplantation. 18 February, 2005 - Rode Zaal, Groningen University Medical Center, Groningen, The Netherlands This symposium focuses on highlighting a number of aspects of artificial organs and organ transplantation in general and bridging to new therapies of end stage organ disease in particular. The meeting is supported by the European Society for Artificial Organs (ESAO) annd the European Society for Organ Transplantation (ESOT). Download the program...

Transportability of bioreactors

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In Vitro Evaluation of the Transportability of Viable Primary Human Liver Cells Originating From Discarded Donor Organs in Bioreactors by Igor M. Sauer, Ruth Schwartlander, Olav van der Jagt, Ingo Steffen, Ekaterina Efimova, Gesine Pless, Daniel C. Kehr, Dimitrios Kardassis, Jan H. Fruhauf, Joerg C. Gerlach, and Peter Neuhaus (Artificial Organs Volume 29 Issue 2 Page 144-151, February 2005) reports on experiments concerning the impact of two major potential threats to viable cells during transport in hollow fiber bioreactors: temperature changes and mechanical stress.
The use of primary human liver cells obtained from discarded donor organs is increasingly favored for cell-based extracorporeal liver support systems. However, as cryopreservation of primary human hepatocytes causes a significant loss of metabolic activity, the transport of bioreactors with viable liver cells is required. The aim of this study was to evaluate the impact of two major potential threats to viable cells during transport: temperature changes and mechanical stress. Methods: In each experiment three hollow fiber-based bioreactors were charged with primary human liver cells originating from the same discarded donor organ and were simultaneously kept under culture conditions for 8 days. In total, 18 bioreactors were evaluated. On the fifth day the bioreactors were exposed to hypothermia (4°C, n = 3), to hyperthermia (42°C, n = 3), or served as normothermic controls (37°C, n = 3). In a second test series bioreactors were exposed to vibration (21 Hz for 20 min, thereafter 7 Hz for 160 min, n = 3), or were operated as control cultures (n = 6). The release of hepatocyte-specific enzymes was determined as an indicator for cell damage. Results: Hypothermic stress resulted in a significant release of transaminases and led to disturbances of the histological integrity, all indicating a high degree of cell damage. When compared with the control cultures, hyperthermia and mechanical stress in terms of vibration had no significant effect on the cells. Conclusion: The transport of hollow fiber bioreactors charged with viable primary human liver cells appears to be feasible in transport monitors for perfusion and temperature control.  

M.I.T. Technology Review: Regenerative Medizin

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Wenn ein Organ ausfällt, braucht der Körper Hilfe. Regenerative Medizin könnte eine Selbstheilung ermöglichen, doch einstweilen braucht es Ersatzteile aus Metall, Plastik oder Silizium. Die aktuelle Ausgabe des Journals M.I.T. Technology Review (Deutsche Ausgabe, November 2004) bringt diverse Artikel zum Thema Regenerative Medizin, unter anderem auch bezüglich des Modular Extracorporeal Liver Support (MELS) Konzept.

Article on "MELS" in top 10 most cited AO articles

The Editor-in-Chief of Artificial Organs informed us that the article "Modular Extracorporeal Liver Support" - published in volume 26, issue 8 of Artificial Organs - was among the top 10 most cited for the year 2003!

FALK Symposium No 145: "Artificial Liver Support"

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Prior to the GASL meeting 2005 the FALK Symposium No 145: "Artificial Liver Support" will take place in Ulm, January 27-28, 2005.
The Falk Symposium No145 on Artificial Liver Support is held to provide an overview on the possibilities and limitations of the up-to-now existing procedures and devices available for artificial liver support. Future perspectives like stem cell differentiation and their therapeutical implications will also be discussed. Leading experts in the field of artificial devices, bioartificial devices, hepatocyte transplantation and stem cells will present the latest data on the various topics, thus promising a very exciting meeting which will be of high interest for all clinicians involved in the treatment of hepatic failure.
More information via
http://www.medkongresse.de/gasl2005/. The program is available here. Registration may be performed via this document.

ESAO 2004: Working Group Liver Support

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For more information on this year's ESAO meeting in Warsaw including the full program please visit http://hrabia.ibib.waw.pl/esao2004/

Evaluation of bioreactor systems

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In vitro comparison test concerning the MELS CellModule and the AMC-BAL are currently performed in cooperation with the Academisch Medisch Centrum (AMC) in Amsterdam...

Hepatology: SPAD vs. MARS

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The paper entitled "In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD)" (Authors: Igor M. Sauer, Max Goetz, Ingo Steffen, Gesa Walter, Daniel C. Kehr, Ruth Schwartlander, Yoon J. Hwang, Andreas Pascher, Joerg C. Gerlach, Peter Neuhaus) is available (HEPATOLOGY 2004;39:1408-1414)!

The detoxification capacities of single-pass albumin dialysis (SPAD), the molecular adsorbents recirculation system, (MARS) and continuous veno-venous hemodiafiltration (CVVHDF) were compared in vitro. In each experiment 4,100 mL of toxin-loaded human plasma was processed for 6.5 hours. MARS treatment (n = 6) was undertaken in combination with CVVHDF. For SPAD (n = 6) and CVVHDF (n = 6) a high-flux hollow fiber hemodiafilter (identical to the MARS filter) was used. Levels of ammonia, urea, creatinine, bilirubin, and bile acids were determined. Concentrations before and after application of detoxification procedures were expressed as differences and were compared using the Kruskal-Wallis test. Post hoc comparisons for pairs of groups were adjusted according to Bonferroni-Holm. Time, group, and interaction effects were tested using the nonparametric ANOVA model for repeated measurements. SPAD and CVVHDF induced a significantly greater reduction of ammonia levels than MARS. No significant differences were found among SPAD, MARS, and CVVHDF with respect to other water-soluble substances. SPAD induced a significantly greater reduction in bilirubin levels than MARS. Reductions in bile acid levels were similar for SPAD and MARS. When operating MARS in continuous veno-venous hemodialysis mode, as recommended by the manufacturer, no significant differences in the removal of bilirubin, bile acids, urea, and creatinine were found. However, MARS in continuous veno-venous hemodialysis mode was significantly less efficient in removing ammonia than MARS in CVVHDF mode. In conclusion, the detoxification capacity of SPAD is similar to or even greater than that of MARS. (HEPATOLOGY 2004;39:1408-1414.)

MELS CellModule vs. AMC-BAL

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Paul Poyck published the results of our in vitro comparison of the two bioartificial liver support systems: MELS CellModule and AMC-BAL (Int J Artif Organs. 2007; 30(3):183-191): Clinically applied bioartificial liver (BAL) support systems are difficult to compare with regard to overall hepatocyte-specific function and clinical outcome. We compared two clinically applied BAL systems, the Modular Extracorporeal Liver Support (MELS) CellModule and the AMC-bioartificial liver (AMC-BAL) in an in vitro set-up. Both BAL systems were loaded with 10 billion freshly isolated porcine hepatocytes, cultured for 7 days and tested on days 1, 2, 4 and 7. Average decrease in hepatocyte-specific functions over 7 days was 9.7%. Three parameters differed between both bioreactors: lidocaine elimination at days 1 and 2 was significantly higher in the AMCBAL, ammonia elimination showed a significantly higher trend for the AMC-BAL over 7 days and LDH release was significantly lower at day 7 for the MELS CellModule. In conclusion, this first in vitro comparison of two clinically applied BAL systems shows comparable functional capacity over a period of 7 days.

Management of Acute Kidney Problems

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Acute kidney failure is an important clinical area in the intensive care unit setting. An estimated 5–20% of critically ill patients experience an episode of acute kidney failure during the course of their illness, and about 5% of patients admitted to an ICU will eventually require renal replacement therapy. In these patients, in-hospital mortality is extremely high, exceeding 50%. Thus, the early detection and causal treatment of acute kidney problems is vitally important for a successful outcome. Written by internationally renowned experts, this clinical reference offers helpful advice with the most recent information on definition, epidemiology, pathophysiology, clinical causes of acute kidney failure, differential diagnostic approaches for patients with acute renal failure, and various key aspects related to the adequate delivery of acute renal replacement therapy.
It also gives a detailed outline of important measures for their clinical management. This reference is intended as a helpful guide for all clinicians involved in the care of patients at risk of developing acute kidney problems.

The book is written for all clinicians who are involved in the care of patients at risk of developing acute kidney problems; e.g. fellows and residents in nephrology, intensive care, internal medicine, anaesthesiology, surgery, paediatrics, diagnostic and interventional radiology, urology, cardiology and clinical immunology.

SPAD in children with acute liver failure

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Hannelore Ringe published the investigations concerning the applicability, efficacy, and safety of single-pass albumin dialysis in children ("Continuous veno-venous single-pass albumin hemodiafiltration in children with acute liver failure." Pediatr Crit Care Med. 2010 Oct 1. [Epub ahead of print]). Co-authors are Varnholt V, Zimmering M, Luck W, Gratopp A, König K, Reich S, Sauer IM, Gaedicke G, and Querfeld U.
The paper reports on a retrospective data review of uncontrolled clinical data of an university-based pediatric intensive care unit collaborating with a local center for liver transplantation.  Nine children, aged 2 to 15 yrs, who were treated with single-pass albumin dialysis for acute liver failure of various origins under a compassionate-use protocol between 2000 and 2006. All patients met high-urgency liver transplantation criteria. Single-pass albumin dialysis was performed as rescue therapy for children with acute liver failure. The decrease in hepatic encephalopathy (grades 1-4) and the serum levels of bilirubin, bile acids, and ammonium were measured to assess the efficacy of detoxification. As a measure of liver synthesis function, thromboplastin time and fibrinogen were analyzed. The safety of the procedure was assessed by documenting adverse effects on mean arterial blood pressure, platelet count, and clinical course. Seven out of nine patients were bridged successfully to either native organ recovery (n = 1) or liver transplantation (n = 7), one of them twice. Six out of nine patients undergoing single-pass albumin dialysis (ten treatments) survived. In six patients, hepatic encephalopathy could be reduced at least by one degree. Ammonium, bilirubin, and bile acid levels decreased in all patients. One patient had an allergic reaction to albumin. In childhood acute liver failure, treatment with single-pass albumin dialysis was generally well tolerated and seems to be effective in detoxification and in improving blood pressure, thus stabilizing the critical condition of children before liver transplantation and facilitating bridging to liver transplantation. It may be beneficial in avoiding severe neurologic sequelae after acute liver failure and thereby improve survival. Single-pass albumin dialysis is an inexpensive albumin-based detoxification system that is easy to set up and requires little training. Whether and to what extent single-pass albumin dialysis can support children with acute liver failure until native liver recovery remain unclear.