Liver Dialysis: A Review

Abstract

Liver dialysis, like kidney dialysis for end-stage kidney disease, refers to the use of extracorporeal devices for temporary support when the liver fails. Unlike the toxemia of kidney failure, the toxins that are retained in the blood when the function of the liver becomes severely deranged, including many protein bound as well as water soluble toxins. These include small molecular weight toxins (ammonia, phenol, false neurotransmitters, free bile acids, etc.) also mediators of inflammation (e.g. cytokines, chemokines) vasoactive substances, cell growth inhibitors (e.g. TGFβ1) and endotoxin.1 Their exact role in causing neurological and other organ impairment and in aggravating injury to the liver, remains undetermined. The beneficial effects, clinically, of clearing the blood of such toxins were shown very early in the history of temporary liver support when exchange transfusion was tried in patients with fulminant hepatic failure and shown to be followed by temporary improvements in encephalopathy. A similar application was returned 10 years later with the use of plasma exchange.2 This approach was taken further in 1994, by Fin Larsen of the Copenhagen Liver Unit. The technique that he developed was of high volume plasmapheresis where 16% of the body weight is exchanged with FFP daily.3 The controlled clinical trial that he set up in patients with acute liver failure (ALF) closed in 2009, with 182 patients entered. According to a personal communication from him, around 20% survival benefit was in the group of patients who were not transplanted. The two pathways of development in liver support devices, namely artificial and bioartificial, are based on different premises (Box 1). Whether there is a need to provide supplementary metabolic and synthetic functions in addition to efficient removal of toxic substances in improving survival, is of fundamental importance. The findings to date with respect to the provision of greater synthetic and metabolic function are, in the writer’s opinion, unconvincing. This is possibly because many of the cell lines are used in the biological modules whether porcine, primary human, tumor cell subclones or immortalized human hepatocyte preparations have limitations in terms of functional capacity. The first major controlled clinical trial of a bioartificial device which was carried out by Demetriou, a pioneer in this field, gave disappointing results in patients with fulminant hepatic failure or primary graft failure without a statistically significant improvement in overall survival (Box 2). The study also illustrated the profound impact of transplantation on survival in ALF, which makes analysis of a possible beneficial effect from the device extraordinarily difficult.4 More encouraging results with respect to survival were reported in a recently conducted trial of extracorporeal liver assist device (ELADTM) based on a tumor cell clone which has been greatly improved over the years.5 This was carried out in China (Box 3) and led the manufacturers – Vital Therapies Inc, San Diego Ca, to set up a multicenter controlled clinical trial initially in the USA. Early findings from this (Box 4), on the safety and efficacy of the device were reported at Key Functions of Liver Devices