Patient Information

Acute liver failure (ALF) is a devastating condition in which subjects with no previous history of liver disease can develop life-threatening multiorgan failure within weeks of the first symptoms. ALF is characterised by massive liver cell death leading to loss of essential metabolic and synthetic functions and a deranged inflammatory response. Consequently, jaundice, coagulopathy, hepatic encephalopathy and multiorgan failure develop rapidly. Mortality from acute liver failure (ALF) is high despite maximal supportive intensive care treatment: 60-80 % depending on the cause. Orthotopic liver transplantation (OLT) is at present the best therapy with one-year survival rates ranging between 50 and 75 % (Bismuth et al 1996). However, the scarcity of donor livers is limiting this therapy; in the Eurotransplant zone there was a need for 2249 liver transplants in 2006, while only 1277 liver transplantations were carried out (www.eurotransplant.nl). In the US, probably ALF accounts for about 6% of the OLTs among adults (Seaberg et al., 1999). The low number of donor livers leads to long waiting times on the OLT waiting list and deaths in up to 20-30% patients waiting for a suitable donor organ to become available. As the liver has an enormous capacity for regeneration, recovery is possible even in patients who have severe liver injury or undergo substantial liver resection.

Bioartificial liver (BAL)-support will either prolong the waiting period for an adequate graft or promote the regeneration capacity of the diseased liver, in the latter case rendering OLT superfluous. This liver support method is therefore promising as it can provide vital life support for ALF patients. Several different types of BAL's are currently under investigation. Most of them are in experimental stages. A few of them have been tested clinically in a Phase 1 study, two of which have been tested in a controlled clinical trial in patients with acute liver failure waiting for transplantation (Strain and Neuberger 2002). Until now they appear to be safe and those BAL's which use porcine hepatocytes as a biocomponent did not show any sign of transmission of endogenous porcine retroviruses (PERV) to the patient.

The AMC-BAL has been succesfully used in a Phase 1 study in Italy in 12 patients with acute liver failure. The treatment appeared to be safe without important adverse effects and without transmission of PERV (Di Nicuolo et al, 2005). Eleven of the twelve patients were successfully bridged to transplantation; one patient recovered during BAL treatment and did not need liver transplantation (see publication of the first 8 patients in: van de Kerkhove et al 2002). The use of the AMC-BAL is, however, still not allowed in many European countries (including the Netherlands), because of a moratorium on xenotransplantation.

For these reasons our research group has started the development of immortalized human hepatocytes (either by genetic manipulation of fetal human hepatocytes or by the culturing of human stem cells, see Hoekstra and Chamuleau 2002). If these cells are available in sufficient amounts with adequate liver cell functions, then there is also an opening to treat Dutch patients with the AMC-BAL.

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