M Ott1, T Cantz, A Schneider, M P Manns. 1. Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland.
Abstract
BACKGROUND: In Germany about 200 patients suffer from acute liver failure each year. Due to its rare occurrence and the severity of the disease course only few evidence-based therapeutic strategies are available. OBJECTIVES: This review aims to discuss the most important developments for the diagnosis and therapy of acute liver failure and provides an outlook of their future clinical relevance. RESULTS: The established enzyme parameters combined with synthesis- and detoxification-related markers insufficiently predict the severity and disease course of acute liver failure. In future, levels of released microRNAs or cleaved cytokeratin 18 fragments may improve the diagnostic repertoire. Currently, only few drug-based therapeutic approaches are available, but much effort has been invested in artificial liver support devices. Based on their favorable risk assessment cell-free detoxification systems are applied sporadically during the treatment of patients with advanced liver diseases, even if to date larger studies have failed to prove a significant survival benefit. Extracorporeal liver assist devices and cell transplantation approaches rely on the availability of metabolically active donor hepatocytes and, thus, the generation of liver cells from appropriate stem cells is gaining interest. CONCLUSION: Current research in stem cell biology and tissue engineering suggest in initial animal studies the feasibility of stem cell-based artificial liver support systems for future treatment of acute liver failure.
BACKGROUND: In Germany about 200 patients suffer from acute liver failure each year. Due to its rare occurrence and the severity of the disease course only few evidence-based therapeutic strategies are available. OBJECTIVES: This review aims to discuss the most important developments for the diagnosis and therapy of acute liver failure and provides an outlook of their future clinical relevance. RESULTS: The established enzyme parameters combined with synthesis- and detoxification-related markers insufficiently predict the severity and disease course of acute liver failure. In future, levels of released microRNAs or cleaved cytokeratin 18 fragments may improve the diagnostic repertoire. Currently, only few drug-based therapeutic approaches are available, but much effort has been invested in artificial liver support devices. Based on their favorable risk assessment cell-free detoxification systems are applied sporadically during the treatment of patients with advanced liver diseases, even if to date larger studies have failed to prove a significant survival benefit. Extracorporeal liver assist devices and cell transplantation approaches rely on the availability of metabolically active donor hepatocytes and, thus, the generation of liver cells from appropriate stem cells is gaining interest. CONCLUSION: Current research in stem cell biology and tissue engineering suggest in initial animal studies the feasibility of stem cell-based artificial liver support systems for future treatment of acute liver failure.
Authors: Eva Warlich; Johannes Kuehle; Tobias Cantz; Martijn H Brugman; Tobias Maetzig; Melanie Galla; Adam A Filipczyk; Stephan Halle; Hannes Klump; Hans R Schöler; Christopher Baum; Timm Schroeder; Axel Schambach Journal: Mol Ther Date: 2011-02-01 Impact factor: 11.454
Authors: P J Starkey Lewis; M Merz; P Couttet; O Grenet; J Dear; D J Antoine; C Goldring; B K Park; J G Moggs Journal: Clin Pharmacol Ther Date: 2012-07-25 Impact factor: 6.875
Authors: Amar Deep Sharma; Nidhi Narain; Eva-Maria Händel; Marcus Iken; Nishant Singhal; Toni Cathomen; Michael P Manns; Hans R Schöler; Michael Ott; Tobias Cantz Journal: Hepatology Date: 2011-03-11 Impact factor: 17.425
Authors: Achilles A Demetriou; Robert S Brown; Ronald W Busuttil; Jeffrey Fair; Brendan M McGuire; Philip Rosenthal; Jan Schulte Am Esch; Jan Lerut; Scott L Nyberg; Mauro Salizzoni; Elizabeth A Fagan; Bernard de Hemptinne; Christoph E Broelsch; Maurizio Muraca; Joan Manuel Salmeron; John M Rabkin; Herold J Metselaar; Daniel Pratt; Manuel De La Mata; Lawrence P McChesney; Gregory T Everson; Philip T Lavin; Anthony C Stevens; Zorina Pitkin; Barry A Solomon Journal: Ann Surg Date: 2004-05 Impact factor: 12.969