Safety Observations in Phase I Clinical Evaluation of the Excorp Medical Bioartificial Liver Support System after the First Four Patients

Abstract

A Phase I clinical safety evaluation of the Excorp Medical, Inc, Bioartificial Liver Support System (BLSS) is in progress. Inclusion criteria are patients with acute liver failure of any etiology, presenting with encephalopathy deteriorating beyond Parson's Grade 2. The BLSS consists of a blood pump, heat exchanger to control blood temperature, oxygenator to control oxygenation and pH, bioreactor, and associated pressure and flow alarm systems. Patient liver support is provided by 70-100 g of porcine liver cells housed in the hollow fiber bioreactor. A single support period evaluation consists of 12 hour extracorporeal perfusion with the BLSS sandwiched between 12 hours of pre (baseline) and 12 hours of post support monitoring. Blood chemistries and hematologies are obtained every 6 hours during monitoring periods and every 4 hours during perfusion. Physiologic parameters are monitored continuously. The patient may receive a second treatment at the discretion of the clinical physician. Preliminary evaluation of safety considerations after enrollment of the first four patients (F, 41, acetaminophen induced, two support periods; M, 50, Wilson's disease, one support period; F, 53, acute alcoholic hepatitis, two support periods; F, 24, chemotherapy induced, one support period) is presented. All patients tolerated the extracorporeal perfusion well. All patients presented with hypoglycemia at the start of perfusion, treatable by IV dextrose. Transient hypotension at the start of perfusion responded to an IV fluid bolus. Only the second patient required heparin anticoagulation. No serious or unexpected adverse events were noted. Moderate biochemical response to support was noted in all patients. Completion of the Phase I safety evaluation is required to fully characterize the safety of the BLSS.

Current development of bioreactors for extracorporeal bioartificial liver (Review)

“…There was another study that reported four cases with ALF treated with BLSS. 112 All the four patients could tolerate the treatment well, and the average levels of ammonia and total bilirubin levels were lower than before treatment by 33% and 6%. During the hemoperfusion, except for the hypoglycemia of four patients at the start phase, and the low blood pressure of one patient that was corrected promptly, there were no other serious complications.…”

“…Cells are mixed with collagen to infuse into hollow fiber bioreactor so that collagen gel matrix is formed in the extracapillary region for cell anchorage. 112 Detry et al 113 developed HepatAssist 2000, in which collagen-coated dextran microcarriers are used for porcine hepatocytes attached and are housed in the extracapillary compartment in the bioreactor. 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.…”

Present and Future Developments in Hepatic Tissue Engineering for Liver Support Systems

“…The cells mixed with collagen are infused into the extracapillary space of fibers. Following the 12-h treatment, PERV transmission from the animal cells to patients was not observed (Mazariegos et al 2001;Kuddus et al 2002). Survival outcome has not been reported for this system.…”

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].…”