Nonbiological Liver Support: Historic Overview

Abstract

An effective hepatic assist system could serve as a bridge to transplantation or to treat acute or chronic hepatic failure. Early nonbiological approaches focused on the removal of low molecular weight toxins by dialysis or hemoperfusion, such as over charcoals or resins. This approach led to clinical trials that showed varying degrees of success. Introduction of more porous membranes and blood separation technologies stimulated the development of plasma exchange, on-line plasma fractionation technologies with sorbents and membranes, and other schemes of sorbent-blood interactions based on the principles of dialysis and hemofiltration with sorbent perfusion. Although detoxification of blood has improved the prognosis for acute liver failure, key issues of when to initiate treatment and by which method need to be resolved. In chronic liver disease, blood detoxification can be applied in patients intractable to conventional therapies and for some awaiting transplantation to relieve disease symptoms such as pruritus, jaundice, elevated bile acids, hyperbilirubinemia, endotoxemia, and hypercholesterolemia. Although biological support is considered the ideal, nonbiological techniques can be useful because hepatocytes possess a regenerative capacity and temporary support is helpful. Available nonbiological liver support technologies can substitute for select liver functions in acute and chronic disease.

Selective plasma filtration for treatment of fulminant hepatic failure induced by D-galactosamine in a pig model

“…However, its major disadvantage is loss of substances from plasma that may promote hepatic regeneration. 9 The components in plasma can be separated according to their size using a selective plasma filter. This process is called selective plasma filtration.…”

Extracorporeal support and hepatocyte transplantation in acute liver failure and cirrhosis

“… 23 Improved survival in ALF has not been convincingly demonstrated with any of the other artificial systems listed above. 5,24 …”

“…Compared with charcoal haemoperfusion alone, removal of tightly protein‐bound compounds is enhanced by perfusion over resins or albumin, while reduction in ammonia levels is achieved by dialysis or perfusion over resins. 24,26–28 The BioLogic‐DT TM system uses a flat‐bed cellulose membrane for haemodialysis against a suspension of powdered charcoal (with a surface area substantially greater than that of granules or beads in a column) and cation exchange resin. 29 Nonetheless, clearance of solutes is limited to those which are permeable through the cellulose membrane, such that removal of highly protein‐bound compounds including unconjugated bilirubin remains limited.…”

“…An additional, although unproven, concern with some artificial systems is that treatment may remove hepatotrophic factors essential for liver regeneration, such as hepatocyte growth factor (HGF) and transforming growth factor‐alpha (TGFα). 24,41 …”

MARS (Molecular Adsorbent Recycling System) als neues Verfahren zum Ersatz der Leberentgiftungsfunktion bis zur orthotopen Lebertransplantation

“…Medikamentös-therapeutische Maûnahmen zur Toxinelimination sind in ihrer Effektivität limitiert, entsprechend besteht ein Bedarf an extrakorporalen Verfahren, die eine effektive Detoxifikation überbrückend bis zur Leberregeneration oder bis zur Verfügbarkeit eines geeigneten Spenderorgans zur orthotopen Lebertransplantation gewährleisten. Aufgrund der hohen Eiweiûbindung der meisten endogenen Toxine sind extrakorporale Verfahren wie Hämodialyse oder Hämofiltration beim Leberversagen nur unzureichend wirksam [3,4]. Eine neue Methode speziell zur Detoxifikation albumingebundener Toxine konnte mit dem ¹Molecular Adsorbent Recycling Systemª (MARS), einer Albumindialyse über eine spezielle Membran, eingeführt werden [5,6].…”