Phase I Clinical Trial with the AMC-Bioartificial Liver

Abstract

Recently a bio-artificial liver (BAL) system has been developed at the Academic Medical Center (AMC) of Amsterdam to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT). After successful testing of the AMC-BAL in rodents and pigs with ALF, a phase I study in ALF patients waiting for (OLT) was started in Italy. We present the safety outcome of the first 7 patients aged 21–56 years with coma grade III or IV. The total AMC-BAL treatment time ranged from 8 to 35 hours. Three patients received 2 treatments with two different BAL's within three days. Six of the 7 patients were successfully bridged to OLT. One patient showed improved liver function after two treatments and did not need OLT. No severe adverse events of the BAL treatment were noted. Conclusion Treatment of ALF patients with the AMC-BAL is a safe and feasible technique to bridge the waiting time for an adequate liver-graft.

Problems and prospects of creation of extracorporal systems for support of functional livers status

“…Различия в конструкции таких биореакторов заключаются в методах прикрепления гепатоцитов. Так, в аппарате ELAD (Extracorporeal liver assist device) гепатоциты человека С3А располагают в экстралюминальном пространстве волокон [36], в аппарате BLSS (Bioartificial liver support system) используют суспензию гепатоцитов свиней в коллагеновом геле [84], в устройстве для аппарата HepatAssist 2000 [85] для иммобилизации гепатоцитов свиней использовали декстрановые микрочастицы, а в апаратах фирмы Academic Medical Center -гидрофильный матрикс на основе полиэфиров [86]. В 2001 году была предложена конструкция MELS (Modular extracorporeal liver support) с более сложным катриджем, состоящим из трёх компартментов полых волокон, выполняющих функции перемещения плазмы, обеспечения гепатоцитов кислородом и питательными веществами [87].…”

Current development of bioreactors for extracorporeal bioartificial liver (Review)

“…The Academic Medical Center ͑AMC͒ EBAL system loads a nonwoven hydrophilic polyester matrix in the extrafiber region in the bioreactor for hepatocytes' attachment while the inner-lumen of hollow fibers are used for oxygen supply. 114 Sauer et al 115 developed a modular extracorporeal liver support ͑MELS͒ with a more complex interwoven hollow fiber cartridge. Three different bundles of hollow fibers are interwoven to form a threedimensional framework so that each bundle can perform separate functions such as plasma inflow, plasma outflow, and oxygen supply.…”

“…114 In the study, seven cases of coma grade III or IV ALF patients received 8-35 h of treatment with AMC-BAL. All patients had improved neurological function, and the blood concentrations of bilirubin and ammonia decreased by 31% and 44%.…”

Functional evaluation of a new bioartificial liver system in vivo and in vivo

“…Continuous O2 input could ensure hepatocytes to gain sufficient oxygen. Therefore, our BAL device has such a novelty as it uses hepatocyte spheroids and serum-free medium compared to previously reported BAL [13][14][15][16] . Experiments of BAL in vitro showed that TB and ALB levels in hepatocyte suspensions and in RPMI-1640 media increased during 6 h of circulation.…”

“…Some systems use hepatocytes attached to microcarrier beads or multicellular spheroid aggregates [9][10][11] . In regard to bioreactor design, various bioreactor configurations have been proposed that employ glass plates, hollow fiber membranes, encapsulation in biological matrices, and 3-dimensional carrier materials [12][13][14][15] . In this study, porcine hepatocytes were isolated by in situ recirculating collagenase perfusion method and cultured with spinner culture method to prepare hepatocyte spheroids.…”