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Liver Support Systems (liver + support_system)
Selected AbstractsEvaluation of Liver Support Systems for Preclinical Testing by Animal TrialsARTIFICIAL ORGANS, Issue 10 2006Oleksandr Seleverstov Abstract:, In the present review, various animal models of acute liver failure are reviewed with respect to their suitability for evaluating liver support systems (LSS) according to envisaged modes of therapy. In order to increase the value of the preclinical testing of LSS, it would be advantageous to include more than one animal model in the evaluation program. It is possible to identify appropriate sets of models, which make a suitable test system for particular clinical applications. A standardization of evaluation methods between testing groups would also be beneficial to the field of liver support. [source] Artificial and bioartificial support systems for liver failure: a Cochrane Hepato-Biliary Group ProtocolLIVER INTERNATIONAL, Issue 5 2002Jianping Liu Abstract: Aims/Background: Liver support systems may bridge patients to liver transplantation or recovery from liver failure. This review is to evaluate the beneficial and harmful effects of artificial and bioartificial support systems for acute and acute-on-chronic liver failure. Data Sources: Randomized trials on any support system versus standard medical therapy will be included irrespective of publication status or language. Non-randomized studies are included in explorative analyses. Trials will be identified through bibliographies, correspondence with original investigators, and electronic searches (Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Controlled Trials Register, MEDLINE, EMBASE, and The Chinese Biomedical Database). Methods of the review: The extracted data will include characteristics of trials, patients, interventions, and all outcome measures. Methodological quality will be assessed by the randomization, follow up, and blinding. The RevMan and STATA will be used for statistical analyses. Sources of heterogeneity and methodological quality in the assessment of the primary outcome will be explored by sensitivity analyses and meta-regression. [source] Changes in Plasma Amino Acids During Extracorporeal Liver Support by Fractionated Plasma Separation and AdsorptionARTIFICIAL ORGANS, Issue 2 2010Kinan Rifai Abstract In patients with liver failure, amino acid dysbalance is common and associated with hepatic encephalopathy. Prometheus is a newly designed extracorporeal liver support system based upon fractionated plasma separation and adsorption (FPSA). We evaluated the influence of FPSA on plasma amino acid patterns in patients with liver failure and hepatic encephalopathy. We studied nine patients with acute-on-chronic liver failure, hepatic encephalopathy, and concomitant renal failure. A single session of FPSA therapy for 5 ± 1 h was performed in all patients. Twenty-six different plasma amino acids were measured by high-performance liquid chromatography before and after FPSA treatment. Total amino acids as well as Fischer index were calculated. Additionally, a variety of clinical and biochemical parameters were assessed. Before FPSA was started, plasma levels of most amino acids were elevated. Plasma ammonia levels correlated with glutamine levels (P < 0.04). During FPSA, plasma levels of nearly all amino acids significantly decreased except for branched-chain amino acids. The Fischer index improved without reaching statistical significance. FPSA therapy tends to normalize plasma amino acids in patients with combined liver and renal failure. This may contribute to positive pathophysiologic effects, especially on hepatic encephalopathy. However, the clinical significance of these findings needs to be further evaluated. [source] Hepatocyte Function in a Radial-flow Bioreactor Using a Perfluorocarbon Oxygen CarrierARTIFICIAL ORGANS, Issue 11 2005Martin J. Nieuwoudt Abstract:, The aims of this study were, first, to indicate the metabolic activity of hepatocytes in a radial-flow polyurethane foam matrix bioreactor relative to monocultures, and second, to evaluate the effect on the hepatocytes of including a synthetic perfluorocarbon (PFC) oxygen carrier to the recirculating medium. The efficient O2 -carrying ability of PFCs may be beneficial to bioreactors employed in stressed cellular environments. Thus, they may also be useful in the treatment of an acute liver failure patient with a bioartificial liver support system (BALSS). Data on the function of three-dimensional (3-D) hepatocyte cultures exposed to emulsified PFCs are lacking. Results: the metabolic functions of the 3-D hepatocyte cultures were improved relative to monocultures. Three-dimensional cultures with and without PFC behaved similarly, and no adverse effects could be detected when PFC was included in the recirculating medium. The addition of PFC significantly improved lidocaine clearance possibly due to the presence of higher O2 tension in the medium. Imaging indicated that large aggregates formed and that seeding had followed flow through the matrix. Simulations indicated first, that the cell numbers used in this study had been insufficient to challenge the bioreactor O2 supply explaining the similarity in performance of the 3-D cultures, and second, that the benefit of adding PFC would be more pronounced at the cell densities likely to be used in a BALSS bioreactor. [source] Enhanced proliferation and differentiation of rat hepatocytes cultured with bone marrow stromal cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2001Toru Mizuguchi Liver transplantation is the only clinically effective method of treating acute liver failure. However, wider application of this therapeutic modality is restricted primarily by shortage of donor organs. In the search for alternative methods of liver replacement therapy, investigators have focused on transplantation of normal allogeneic hepatocytes and on the development of liver support systems utilizing isolated hepatocytes. Since all human livers suitable for cell harvest are being used for transplantation, hepatocyte therapy using human tissue would require growing of cells in vitro. Unfortunately, although hepatocytes have tremendous capacity to proliferate in vivo, their ability to grow in culture is severely limited. Stromal cells from bone marrow and other blood-forming organs have been found to support hematopoiesis. In this paper, we show that bone marrow-derived stromal cells (BMSCs) enhance proliferation and support differentiation of rat hepatocytes in culture. Further, we demonstrate that in hepatocyte/BMSC co-cultures, clonal expansion of small hepatocytes (SH) is increased. Using semipermeable membrane cultures, we established that direct cell,cell contact is necessary for stimulation of cell proliferation. We also show that BMSCs which are in direct contact with hepatocytes and SH colonies express Jagged1. This suggests a potential role for Notch signaling in the observed effects. Finally, we present evidence that the expression and activity of liver specific transcirption factors, CCAAT/enhancer binding proteins and liver specific key enzymes such as tryptophan 2,3-dioxygenase, are improved in hepatocyte/BMSC co-cultures. In conclusion, results of this study indicate that BMSCs could facilitate proliferation and differentiation of primary rat hepatocytes and their progenitors (SH) in vitro. © 2001 Wiley-Liss, Inc. [source] Review article: the current management of acute liver failureALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010D. G. N. CRAIG Aliment Pharmacol Ther,31, 345,358 Summary Background, Acute liver failure is a devastating clinical syndrome with a persistently high mortality rate despite critical care advances. Orthotopic liver transplantation (OLT) is a life-saving treatment in selected cases, but effective use of this limited resource requires accurate prognostication because of surgical risks and the requirement for subsequent life-long immunosuppression. Aim, To review the aetiology of acute liver failure, discuss the evidence behind critical care management strategies and examine potential treatment alternatives to OLT. Methods, Literature review using Ovid, PubMed and recent conference abstracts. Results, Paracetamol remains the most common aetiology of acute liver failure in developed countries, whereas acute viral aetiologies predominate elsewhere. Cerebral oedema is a major cause of death, and its prevention and prompt recognition are vital components of critical care support, which strives to provide multiorgan support and ,buy time' to permit either organ regeneration or psychological and physical assessment prior to acquisition of a donor organ. Artificial liver support systems do not improve mortality in acute liver failure, whilst most other interventions have limited evidence bases to support their use. Conclusion, Acute liver failure remains a truly challenging condition to manage, and requires early recognition and transfer of patients to specialist centres providing intensive, multidisciplinary input and, in some cases, OLT. [source] Hepatic tissue engineering for adjunct and temporary liver support: Critical technologiesLIVER TRANSPLANTATION, Issue 11 2004Christina Chan The severe donor liver shortage, high cost, and complexity of orthotopic liver transplantation have prompted the search for alternative treatment strategies for end-stage liver disease, which would require less donor material, be cheaper, and less invasive. Hepatic tissue engineering encompasses several approaches to develop adjunct internal liver support methods, such as hepatocyte transplantation and implantable hepatocyte-based devices, as well as temporary extracorporeal liver support techniques, such as bioartificial liver assist devices. Many tissue engineered liver support systems have passed the "proof of principle" test in preclinical and clinical studies; however, they have not yet been found sufficiently reliably effective for routine clinical use. In this review we describe, from an engineering perspective, the progress and remaining challenges that must be resolved in order to develop the next generation of implantable and extracorporeal devices for adjunct or temporary liver assist. (Liver Transpl 2004;10:1331,1342.) [source] Lidocaine/Monoethylglycinexylidide Test, Galactose Elimination Test, and Sorbitol Elimination Test for Metabolic Assessment of Liver Cell BioreactorsARTIFICIAL ORGANS, Issue 6 2010Jörg C. Gerlach Abstract Various metabolic tests were compared for the performance characterization of a liver cell bioreactor as a routine function assessment of cultures in a standby for patient application in clinical studies. Everyday quality assessment (QA) is essential to ensure a continuous level of cellular functional capacity in the development of hepatic progenitor cell expansion systems providing cells for regenerative medicine research; it is also of interest to meet safety requirements in bioartificial extracorporeal liver support systems under clinical evaluation. Quality criteria for the description of bioreactor cultures were developed using primary porcine liver cells as a model. Porcine liver cells isolated by collagenase perfusion with an average of 3 × 109 primary cells were used in 39 bioreactors for culture periods up to 33 days. Measurements of monoethylglycinexylidide synthesis and elimination of lidocaine, galactose elimination, and sorbitol elimination proved to be useful for routine QA of primary liver cell cultures. We demonstrate two methods for dispensing test substances, bolus administration and continuous, steady-state administration. Bolus test data were grouped in Standard, Therapy, Infection/Contamination, and Cell-free control groups. Statistical analyses show significant differences among all groups for every test substance. Post hoc comparisons indicated significant differences between Standard and Cell-free groups for all elimination parameters. For continuous tests, results were categorized according to number of culture days and time-dependent changes were analyzed. Continuous administration enables a better view of culture health and the time dependency of cellular function, whereas bolus administration is more flexible. Both procedures can be used to define cell function. Assessment of cellular function and bioreactor quality can contribute significantly to the quality of experimental or clinical studies in the field of hepatic bioreactor development. [source] Evaluation of Liver Support Systems for Preclinical Testing by Animal TrialsARTIFICIAL ORGANS, Issue 10 2006Oleksandr Seleverstov Abstract:, In the present review, various animal models of acute liver failure are reviewed with respect to their suitability for evaluating liver support systems (LSS) according to envisaged modes of therapy. In order to increase the value of the preclinical testing of LSS, it would be advantageous to include more than one animal model in the evaluation program. It is possible to identify appropriate sets of models, which make a suitable test system for particular clinical applications. A standardization of evaluation methods between testing groups would also be beneficial to the field of liver support. [source] | ||||||||||