Withdrawal

Abstract

One of the cardinal features of any liver replacement therapy is the ability to remove accumulated metabolites. The removal of water-soluble substances by dialysis procedures is well established. However, an unsolved problem is the low dialyzability of lipophilic toxins. This study aimed to explore whether bilirubin and bile acids removal can be increased by free fatty acid (FFA) displacement and its combination with albumin dialysis. First, we found that the protein binding of both bilirubin and bile acids decreased significantly with increasing FFA concentrations when co-incubated directly. Then, in vitro dialysis showed that fatty acid mixtures ([linoleic acid] / [oleic acid] = 2) infusion pre-filter effectively increased the fractional removal of bilirubin and bile acids from 1.43 ± 0.07% and 2.50 ± 0.12%, to 10.04 ± 0.29% and 6.12 ± 0.07%, respectively, which were significantly higher than albumin-based hemodialysis (HD); in vivo dialysis showed that lipid emulsion administration resulted in higher reduction ratios and more total solute removals for bilirubin and bile acids after 4 h HD compared with control, which was also superior to albumin-based HD. Finally, the highest dialysis efficacy was always observed by their combination whether in vitro or in vivo. These findings highlight that FFA displacement-based HD could efficiently improve the dialytic removal of bilirubin and bile acids, whilst its dialysis efficacy might even be superior to albumin-based HD. The concept of their combination may open up new avenues and possibilities in the field of dialysis to further enhance lipophilic toxins removal in liver failure.