Extracorporeal support and hepatocyte transplantation in acute liver failure and cirrhosis

Abstract

The relative shortage of donor organs and lack of immediate availability mean that many patients with acute liver failure die before orthotopic liver transplantation can be performed. An effective temporary liver support system could improve the chance of survival with or without a transplant being ultimately carried out. Recent technological advances resulting in improved maintenance of hepatocyte viability and function in culture and bioreactor designs which facilitate adequate perfusion of the cellular component and removal of products of cellular metabolism have led to the development of a number of bioartificial devices for liver support. Three such devices have undergone preliminary clinical evaluation in the setting of acute liver failure, with a statistically significant reduction in raised intracerebral pressure along with improvements in consciousness level and some biochemical parameters associated with treatment with one of these. Several other devices with different characteristics have shown promise in vitro and/or in animal models but await clinical evaluation. Several new totally artificial systems have also been described, along with the emergence of isolated hepatocyte transplantation, with reports of successful ‘bridging’ to liver transplantation. Controlled trials on a multicentre basis in well‐defined patient groups and with standardized outcome measures will be required to properly evaluate the clinical value of each of these approaches to providing liver support in acute liver failure and cirrhosis. A better understanding of mechanisms underlying multiorgan failure and of factors inhibiting liver regeneration, thereby allowing a more targeted approach, will be essential to the further development of effective liver support strategies in these settings.

Artificial and Bioartificial Support Systems for Acute and Acute-on-Chronic Liver Failure

“…1 The first artificial support systems removed toxins through hemodialysis, hemofiltration, or hemoperfusion. 1,2,7 More recent systems combine hemodialysis with adsorption to charcoal or albumin (hemodiabsorption) 9,10 or use living hepatocytes, which add synthetic functions to the detoxification (bioartificial support systems). 11,12 We performed a systematic review to evaluate the effect of artificial and bioartificial liver support systems for acute and acute-on-chronic liver failure.…”

Detection of PERV by polymerase chain reaction and its safety in bioartificial liver support system

“…EBLSS based on porcine hepatocytes catches more interest as an effective temporary treatment to improve the chance of survival and a bridge to liver transplantation [5,6,[20][21][22][23][24][38][39][40][41] . Because of the shortage of human cells, porcine endogenous retroviruse (PERV), found in 1970's, was focused for its safety in xenotransplantation and treatments based on porcine tissues or cells as vitro infection of human cell lines HEK 293 was demonstrated in 1997 [4,[34][35][36][37] .…”

Review article: non‐biological liver support in liver failure

“…Bioartificial or hybrid devices combine the best of both biological and non-biological techniques. [17][18][19][20] Because most of the data with regard to extracorporeal liver support are available for non-biological support systems, we will further focus on these techniques.…”

“…Major side-effects are hypernatraemia, metabolic alkalosis and a decrease in colloid osmotic pressure. 16,17 There are no randomized trials on plasma exchange and case series reported no improvement in neurological function or mortality, despite improved coagulation parameters and decreased cytokine and endotoxin load. 86,87 High-volume plasmapheresis (HVP) is a more extreme method of plasma exchange and consists of exchanging more than 10 L of plasma.…”