Bioartificial liver treatment prolongs survival and lowers intracranial pressure in pigs with fulminant hepatic failure

Intracranial hypertension leading to brainstem coning is a major cause of d eath in fulminant hepatic failure (FHF). We have developed a bioartificial liver (BAL) utilizing plasma perfusion through a bioreactor loaded with por cine hepatocytes and a column with activated charcoal. In a Phase I clinica l trial, we observed a decrease in intracranial pressure (ICP) in FHF patie nts. However, these patients received BAL therapy together with other measu res. We therefore examined whether BAL therapy alone could prevent developm ent of intracranial hypertension in pigs with surgically induced FHF. Pigs (40-60 kg) underwent end-to-side portacaval shunt, transection of all hepat ic ligaments, and placement of slings around the hepatic artery and bile du ct. 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 pi gs (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 ma intained a normal ICP during BAL treatment and for 14 h afterward and becau se of this effect they survived longer than Groups 2 and 3 animals. In cont rast, Groups 2 and 3 pigs showed an early (6-8 h) rise in ICP.