HepaHope Product Publications
International Liver Congress
March 25-28, 2006
SHANGHI, CHINA
In Vitro Assessment of a Novel Porcine Liver Slice-Filled Bio-Artificial Liver (BAL) for Dialysis of Liver Failure Patients
Holger P. Behrsing1, Jennifer Tam1, Brad Gray1, Andy Do1, Young Park1, Hyoung Yoon1, Delai Zhao1, Jaeho Jung1, Robert G. Gish2, Brendan M. McGuire3, Angela Panoskaltsis-Mortari4, George K. K. Lau5, Dongjin Suh6, Sung SooPark1
1HepaHope Inc., 2California Pacific Medical Center, San Francisco, California, 3University of Alabama, 4University of Minnesota, 5Hong Kong University, Queen Mary Hospital, 6University of Ulsan, Asan Medical Center
Due to the large number of patients who die annually from acute liver failure worldwide, the bio-artificial liver has been identified as a medical need. With efficient toxin removal and biochemical function, the new porcine liver slice HepaHope BAL is designed to treat such patients. The BAL contains porcine liver slices with multiple, native cells in well-preserved structures that allow high capacity and efficient removal of toxins in acute hepatic failure patients. Several 6 hour exposure in vitro BAL studies designed to mimic in vivo treatment conditions were conducted to evaluate: 1) ammonia and drug clearance, 2) stability tests under shipping conditions, 3) effects of human anti-Gal on porcine slices, and 4) potential for PERV infection. Studies examining ammonia clearance demonstrated an 88% clearance of ~1000 µg/dL (~590 µM) ammonia in 2 L human plasma (circulation rate ~6L/hour). Clearance of nine drugs commonly administered to liver failure patients (Diazepam, Dopamine, Fentanyl, etc.) indicated a varied metabolism profile, with clearance ranging from 15 to 58% of initial dose. The BAL retained functionality (assessed by ammonia/drug clearance) and histological integrity (by light microscopy) after shipping periods lasting up to 15 hours. Perfusion with human plasma did not appear to adversely effect BAL function, and minimal staining of anti-GAL antibodies was seen after perfusion. Samples of plasma were also studied for PERV; results are pending at the time of this abstract’s submission. CONCLUSION: The favorable pre-clinical in vitro results have led to a series of in vivo studies to further characterize this BAL.
