Publications (176) View all
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Article: Systematic review: acute liver failure - one disease, more than 40 definitions.
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ABSTRACT: Acute liver failure (ALF) is a clinical syndrome with very high mortality estimates ranging between 60% and 80%. To investigate the explicitness and extent of variability in the used ALF definitions in the ALF prognostic literature. All studies that pertain to the prognosis of patients with ALF were electronically searched in MEDLINE (1950-2012) and EMBASE (1950-2012). Identified titles and abstracts were independently screened by three reviewers to determine eligibility for additional review. We included English articles that reported original data from clinical trials or observational studies on ALF patients. A total of 103 studies were included. Of these studies 87 used 41 different ALF definitions and the remaining 16 studies did not report any explicit ALF definition. Four components underlying ALF definitions accounted for the differences: presence and/or grading of hepatic encephalopathy (HE); the interval between onset of disease and occurrence of HE; presence of coagulopathy and pre-existing liver disease. The diversity in acute liver failure definitions hinders comparability and quantitative analysis among studies. There is room for improvement in the reporting of acute liver failure definitions in prognostic studies. The result of this review may be useful as a starting point to create a uniform acute liver failure definition.Alimentary Pharmacology & Therapeutics 04/2012; 35(11):1245-56. · 3.77 Impact Factor -
Article: [Recent developments in the treatment of chronic hepatitis B and C].
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ABSTRACT: Chronic hepatitis B and C are life-threatening diseases, treated with variable success. Peginterferon-alpha is one of the standard therapies for chronic hepatitis B as well as C. To prevent the development of resistant viruses, combination treatment is preferable to monotherapy. Therefore, in chronic hepatitis B virus peginterferon-alpha combined with nucleoside inhibitors is used. The treatment of chronic hepatitis C virus with a combination of peginterferon-alpha and ribavirine can be improved by new protease inhibitors.Nederlands tijdschrift voor tandheelkunde 09/2007; 114(8):353-6. -
Article: In vitro comparison of two bioartificial liver support systems: MELS CellModule and AMC-BAL.
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ABSTRACT: 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.The International journal of artificial organs 04/2007; 30(3):183-91. · 1.86 Impact Factor -
Article: Subnormothermic preservation maintains viability and function in a porcine hepatocyte culture model simulating bioreactor transport.
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ABSTRACT: Bioartificial liver (BAL) systems have been developed to bridge patients with acute liver failure (ALF) to liver transplantation or liver regeneration. Clinical application of BAL systems is dependent on the supportive quality of cells used and direct availability of the whole system. Reliable transport of BAL systems from the laboratory to remote treatment centers is therefore inevitable. Subsequently, preservation conditions play a crucial role during transport of a BAL, with temperature being one of the most determining factors. In this study, we assessed the effect of subnormothermic preservation on freshly isolated porcine hepatocytes cultured in monolayer under oxygenation. Additionally, the effect of the University of Wisconsin (UW) preservation solution was compared with Williams' E (WE) culture medium at 4 degrees C. The control group was cultured for 3 days at 37 degrees C, whereas the transport groups were cultured at 4 degrees C, 15 degrees C, 21 degrees C, or 28 degrees C for 24 h at day 2. All groups were tested each day for cell damage and hepatic functions. Subnormothermic culture (i.e., 15 degrees C to 28 degrees C) for a period of 24 h did not reduce any hepatic function and did not increase cellular damage. In contrast, culture of hepatocytes in WE medium and preservation in UW solution at 4 degrees C significantly reduced hepatic function. In conclusion, freshly isolated porcine hepatocytes can be preserved for 24 h at subnormothermic temperatures as low as 15 degrees C. Future research will focus on the implementation of the AMC-BAL in an oxygenated culture medium perfusion system for transport between the laboratory and the hospital.Cell Transplantation 02/2006; 15(2):161-8. · 5.13 Impact Factor -
Article: Assessment and improvement of liver specific function of the AMC-bioartificial liver.
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ABSTRACT: The variety of methods for measuring bioactive mass and functionality of bioartificial livers (BAL) is confusing and prevents accurate comparison of reported data. Here we present a comparison of different hepatocyte quantification methods and propose that estimation of cell pellet volume after centrifugation generates a reliable, useful and fast method. In addition a correlation is made between several function tests performed in 26 bioreactors to assess their predictive value. The ammonia eliminating capacity was found to be most predictive for other liver functions, except for lidocaine elimination as a measure of mixed function oxidase activity, which should therefore be determined separately. The oxygen consumption test proved to be an easy and predictive parameter as well. The first generation of our BAL system needed further development to assure optimal treatment of acute liver failure (ALF) patients. Changes in the porcine hepatocyte isolation method and bioreactor loading as well as changes in bioreactor configuration, including use of different materials, resulted in a significantly improved level and maintenance of in vitro BAL function. A fourfold increase in ammonia eliminating capacity, which is only reduced to 75% after seven days of culturing, offers promising prospects for further clinical application. Conclusion: The current second generation of our BAL and improvement of hepatocyte isolation and testing protocols have led to a significant increase in the level as well as the maintenance of hepatocyte specific function in our BAL. Finally, consensus on definition of the bioactive mass to be loaded in the bioreactor and insight in the variation and reliability of the functional and metabolic parameters enhances comparison of the different types of bioartificial livers presented in literature.The International journal of artificial organs 07/2005; 28(6):617-30. · 1.86 Impact Factor
