PROSPECTS FOR EXTRACORPOREAL LIVER SUPPORT
Authors: R Jalan
Journal: Gut (2004)

his present review is timely with the increasing use of the molecular adsorbents recirculating system (MARS) for the management of liver failure, with over 3000 patients having been treated with this device worldwide.In the UK, MARS is being used for the treatment of individual patients both in the National Health Service and also in the private sector.In order to investigate the latest position with respect to bioartificial liver devices, a meeting was held at University College London Hospital in September 2003 and this article is based on the most up to date data presented there.Liver failure, whether of the acute variety with no pre-existing liver disease (acute liver failure (ALF)) or an acute episode of decompensation superimposed on a chronic liver disorder (acute on chronic liver failure (ACLF)), carries a high mortality.In patients with ALF, lack of detoxification, metabolic, and regulatory functions of the liver leads to life threatening complications, including kidney failure, encephalopathy, cerebral oedema, severe hypotension, and susceptibility to infections culminating in multiorgan failure. 1 The only established therapy for such patients is liver transplantation (LTx) but currently one third of these patients die while waiting for a transplant and the organ shortage is increasing (fig 1). 2 However, liver failure, whether of the acute or acute on chronic variety, is potentially reversible, and considerable work has been carried out over many years to develop effective liver support devices.The development of these devices has been approached in two very different ways.The biological devices, which aim to provide all of the functions of the normal liver, 3 4 are based on the use of living liver cells with either human hepatic cells as in the extracorporeal liver assist device (ELAD) device 5 or porcine hepatocytes as in the BAL device 6 and in various other European devices being developed in the Netherlands 7 and in Germany. 8The other approach is based on detoxification functions only using membranes and adsorbents which can remove the putative toxins associated with liver failure.Such entirely artificial devices are substantially less costly, by a factor of at least a tenth, than those based on living liver cell lines.The earliest of the artificial systems developed was based on perfusion of the patient's blood through the adsorbent charcoal. 9 10Although some of the toxins present in liver failure were shown to be adsorbed to the charcoal, other compounds tightly bound to proteins in the plasma were not removed. 9 10Another system known as a Biologic-DT is a combination of flat membrane dialysis against adsorbent solution 11 but several studies have shown only limited efficacy in terms of removal of protein bound substances. 3 124][15] In addition to the facility for removing protein bound substances, there is an additional dialysis component for removal of water soluble toxins.In this review, we will define the goals of artificial liver support, discuss the design of the existing liver support systems, and critically analyse the available data from clinical studies to establish their current status in the management of patients with liver failure. BASIS OF USE OF A LIVER SUPPORT DEVICE cAn ideal liver support system would provide many of the normal functions of the liver, be easy to use in clinical practice, have minimal complications, and not be prohibitively expensive.From the pathophysiological perspective, this can be translated to having significant biosynthetic capacity with the ability to detoxify and the capability to biotransform by altering key processes which allows regeneration and healing.Although provision of the biosynthetic function of the liver may be thought to be important, it is possible to provide many of the substances manufactured by the liver, such as glucose, albumin, trace elements and vitamins, and clotting factors either through the oral route or by infusions. 4We believe that the ability of the artificial liver support systems to mimic the detoxification functions of the liver is crucial to their success, as liver failure is associated with accumulation of various toxic substances such as ammonia, mediators of Box 1 Goals of therapy with liver support devices Primary goal c In acute liver failure: recovery of patient to normal health c In acute on chronic liver failure: recovery to the state before decompensation Alternative goals c Bridge to liver transplantation c Prevention of progression to liver failure c Improvement of end organ function in those with established multiorgan failure 891