A Bioartificial Liver to Treat Severe Acute Liver Failure

Abstract

ObjectiveTo test the safety and efficacy of a bioartificial liver support system in patients with severe acute liver failure. Summary Background DataThe authors developed a bioartificial liver using porcine hepatocytes. The system was tested in vitro and shown to have differentiated liver functions (cytochrome P450 activity, synthesis of liverspecific proteins, bilirubin synthesis, and conjugation). When tested in vivo in experimental animals with liver failure, it gave substantial metabolic and hemodynamic support. MethodsSeven patients with severe acute liver failure received a double lumen catheter in the saphenous vein; blood was removed, plasma was separated and perfused through a cartridge containing 4 to 6 X 109 porcine hepatocytes, and plasma and blood cells were reconstituted and reinfused.Each treatment lasted 6 to 7 hours. ResultsAll patients tolerated the procedure(s) well, with neurologic improvement, decreased intracranial pressure (23.0 ± 2.3 to 7.8 ± 1.7 mm Hg; p < 0.005) associated with an increase in cerebral perfusion pressure, decreased plasma ammonia (163.3 ± 21.3 to 1 12.2 ± 9.8 ,uMoles/L; p < 0.01), and increased encephalopathy index (0.60 ± 0.17 to 1.24 ± 0.22; p < 0.03). All patients survived, had a liver transplant, and were discharged from the hospital.

Immortalization of Human Fetal Hepatocyte by Ectopic Expression of Human Telomerase Reverse Transcriptase, Human Papilloma Virus (E7) and Simian Virus 40 Large T (SV40 T) Antigen Towards Bioartificial Liver Support

“…[24][25][26] Primary hepatocytes is ideal source for bioartificial liver device but not practically suitable due such limitations like the availability of these cells is limited, and expansion of human hepatocytes in culture is difficult, even advanced culture condition, still finite number of cell division and then stop. Although the cryopreservation techniques has been suggested as a standard protocol for long term storage liver cell retaining their function.…”

Advances in bioartificial liver devices

“…65,75,79,[87][88][89] Single cell suspensions, used in some devices because of their desirable transport properties, quickly lose metabolic capacity. 90 Some packed bed designs 77,78 and one hollow fiber device 91 seed cells on microcarriers before device assembly. While microcarriers provide Potential stem cell sources…”

Liver stem cells: prospects for treatment of inherited and acquired liver diseases

“…Recent meta-analysis of data from 12 trials, involving 483 patients, confirmed that while the devices were not yet showing efficacy in treatment of acute liver failure, some degree of improved survival was seen in acute-onchronic liver failure [66]. The hepatocyte sources so far include porcine hepatocytes (sometimes cryopreserved) [67][68][69] and a human C3A hepatoma-derived cell line [70,71]. Developers of these devices have been able to address safety concerns of immune reaction, xenozoonosis and tumourigenicity sufficiently to move to Phase II/III clinical trials [65].…”