Toward an Artificial Liver: In Vitro Removal of Unbound and Protein-Bound Plasma Compounds Related to Hepatic Failure

Abstract

We have examined in vitro some requirements for an artificial support system for use in hepatic failure. These experiments compared methods of removing from plasma (1) certain unbound substances implicated in the pathogenesis of hepatic coma, and (2) some model protein-bound substances of variable toxic potential known to be extracted by the liver and excreted in the bile. A Craig thin film countercurrent dialyzer was used, and dialysis rates were related to protein binding by determining concentrations of unbound species by ultrafiltration. Compounds not bound to protein (methionine, glutamine, butyrate, ammonia, and urea) were readily dialyzed (>90%). Dialysis of protein-bound anions (unconjugated bilirubin, chenodeoxycholate, sulfobromophthalein, and methyl orange) was negligible and was enhanced little by addition of a competitive anion (salicylate) or an acceptor (plasma or a water-soluble polycation) to the dialysate. The major rate-limiting factor was the low concentration of unbound species, rather than the membrane. When plasma was passed over columns containing anion exchange or uncharged resins, protein-bound material was removed efficiently; anion exchange resins were superior to uncharged resins. Both hemoperfusion through anion exchange columns and hemodialysis may therefore be essential excretory components of an artificial liver.