Albumin Apheresis for Artificial Liver Support: In Vitro Testing of a Novel Filter

Abstract

Currently there is no direct therapy for liver failure. We have previously described selective plasma exchange therapy using a hemofilter permeable to substances that have a molecular mass of up to 100 kDa. The proof-of-concept studies and a Phase I study in patients with decompensated cirrhosis demonstrated that hemofiltration using an albumin-leaking membrane is safe and effective in removing target molecules, alleviating severe encephalopathy and improving blood chemistry. In this study a novel large-pore filter for similar clinical application is described. The performance of the filter was studied in vitro; it was found to effectively remove a wide spectrum of pathogenic factors implicated in the pathophysiology of hepatic failure, including protein bound toxins and defective forms of circulating albumin. Data on mass transport characteristics and functionality using various modes of filtration and dialysis provide rationale for clinical evaluation of the filter for artificial liver support using albumin apheresis.

In vitro safety and efficacy evaluation of a novel hybrid bioartificial liver system with simulated liver failure serum

“…Presently, a common evaluation method is to use discarded patient plasma obtained by clinical plasma exchange 4 –7 or plasma from animals with liver failure. 8 However, because of individual differences, the related indicators of discarded plasma or animal serum are not uniform, and liver failure serum has a cytotoxic effect, which affects the results of in vitro function evaluation. A study 9 has also utilized the Roswell Park Memorial Institute (RPMI) 1640 culture medium to evaluate the function of an ALS in vitro; however, this does not replicate the actual treatment in patients with liver failure.…”