title: Bioartificial liver treatment prolongs survival and lowers intracranial pressure in pigs with fulminant hepatic failure.
abstract: Intracranial hypertension leading to brainstem coning is a major cause of death in fulminant hepatic failure (FHF). We have developed a bioartificial liver (BAL) utilizing plasma perfusion through a bioreactor loaded with porcine hepatocytes and a column with activated charcoal. In a Phase I clinical trial, we observed a decrease in intracranial pressure (ICP) in FHF patients. However, these patients received BAL therapy together with other measures. We therefore examined whether BAL therapy alone could prevent development of intracranial hypertension in pigs with surgically induced FHF. Pigs (40-60 kg) underwent end-to-side portacaval shunt, transection of all hepatic ligaments, and placement of slings around the hepatic artery and bile duct. After 3 days, the slings were tightened to induce liver necrosis. After 4 h, Group 1 pigs (n = 6) underwent a 6 h treatment with the BAL utilizing 10 billion cryopreserved pig hepatocytes and a charcoal column, Group 2 pigs (n = 6) with the BAL containing charcoal but no cells, and Group 3 pigs (n = 6) with the BAL containing neither cells nor charcoal. Group 1 pigs maintained a normal ICP during BAL treatment and for 14 h afterward and because of this effect they survived longer than Groups 2 and 3 animals. In contrast, Groups 2 and 3 pigs showed an early (6-8 h) rise in ICP.
authors.affiliation: Liver Support Research Laboratory, Department of Surgery, Burns and Allen Research Institute, University of California Los Angeles School of Medicine, Los Angeles, CA 90048, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Khalili
authors.forename: A
authors.initials: A
authors.lastname: Navarro
authors.forename: P
authors.initials: P
authors.lastname: Ting
authors.forename: Y
authors.initials: Y
authors.lastname: Kamohara
authors.forename: N
authors.initials: N
authors.lastname: Arkadopoulos
authors.forename: B A
authors.initials: BA
authors.lastname: Solomon
authors.forename: A A
authors.initials: AA
authors.lastname: Demetriou
authors.forename: J
authors.initials: J
authors.lastname: Rozga
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017690:Cell Transplantation / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D022781:Hepatocytes / Q000637:transplantation; D019586:Intracranial Hypertension / Q000150:complications / Q000401:mortality / Q000628:therapy*; D017093:Liver Failure / Q000150:complications / Q000401:mortality* / Q000628:therapy*; D019164:Liver, Artificial; D011336:Probability; D012680:Sensitivity and Specificity; D015996:Survival Rate; D013552:Swine; D016896:Treatment Outcome