Liver Support Therapy: An Overview of the AMC-Bioartificial Liver Research

Abstract

Acute liver failure (ALF) is a disease with a mortality of 60–90% depending on the cause. Only high-urgency liver transplantation is able to increase survival compared to standard intensive care therapy. Liver transplantation is hampered by the increasing shortage of organ donors, resulting in a high incidence of patients with ALF dying on the transplantation waiting list. Amongst a variety of liver assist therapies, bioartificial liver (BAL) therapy is marked as the most promising solution to bridge ALF patients to liver transplantation or to liver regeneration, since several BAL systems showed significant improvement of survival time in experimental animals with irreversible ALF. One of these systems has been developed at the Academic Medical Center in Amsterdam, The Netherlands – the AMC-BAL. This overview describes the development of the AMC-BAL based on porcine hepatocytes which was started 10 years ago. Positive results of in vitrofunctionality and in vivo safety and efficacy led to a successful phase I study in 12 ALF patients in Italy. However, xenotransplantation legislation in many European countries prohibits the use of porcine hepatocytes in clinically applied BAL systems. The future of the BAL, therefore, resides in the development of a human-derived hepatocyte cell line as biocomponent of BAL systems.

Liver Regenerative Medicine: Advances and Challenges

“…Despite a highly promising start, using extracorporeal liver support systems revealed several serious problems, including quick loss of functional activity and limited ex vivo viability of primary hepatocytes [Xiong et al 2008]. The bioartificial liver device AMC, developed in the Academic Medical Center (Amsterdam) and based on pig hepatocytes, showed favorable results in a phase I clinical trial including the complete recovery of 1 patient and no need for further liver transplant [van de Kerkhove et al, 2005]. However, Fruhauf et al [2009] isolated endogenous reovirus from primary porcine hepatocytes used in the AMC machine capable of infecting cultured primary human hepatocytes.…”

Current development of bioreactors for extracorporeal bioartificial liver (Review)

“…151 With further optimization, dead space in the bioreactor was reduced so that the biofunction of liver cells was kept at 80%-90% of day 1 after 3 day cultivation. 152 In addition, Mareels et al 153 reported their application of rheological numerical model for the optimization the distribution of oxygen in the AMC bioreactor. However, it has yet reported the clinical studies with optimized bioreactor AMC.…”

Stem cells and liver repair

“…The possibilities of cellular transplantation have been discussed earlier in this review, and the main constraints remain to be difficulties in sourcing and maintaining viable hepatocytes. Attempts in immortalisation of primary hepatocytes are currently only partially successful as proliferation and hepatocellular function can appear mutually exclusive [41]. A recently developed human hepatoma cell line HepaRG [42] retains some attributes of primary hepatocytes but nonetheless remains a cancer cell line, and therefore is restricted in their application to in vitro modelling of human drug toxicity and incorporation in extracorporeal support devices.…”