title: Reversal of experimental posthepatectomy liver failure in pigs: a new application of hepatocyte bioreactors.
abstract: Postoperative liver failure remains a major cause of morbidity and mortality after extensive hepatectomies. This study aims to evaluate the effectiveness of a hepatocyte bioreactor in the treatment of experimental post-hepatectomy liver failure. Our experimental model included a combination of a side-to-side portacaval shunt, occlusion of the hepatoduodenal ligament for 150 min, 70% hepatectomy, and reperfusion. Following the development of liver failure, 12 pigs were randomized into a control group (n = 6) and a treatment group (n = 6). Both groups underwent extracorporeal perfusion through a plasma separation device, a membrane oxygenator, and two parallel bioreactors. In the latter group, the bioreactors were loaded with 10 billion fresh hepatocytes, isolated from a donor pig. Following hepatocyte treatment, all animals were maintained for 24 h under mechanical ventilation, with intravenous fluid and glucose supplementation. Hemodynamic parameters, intracranial pressure, and biochemical parameters were measured. Liver biopsies were obtained during the 24-h autopsy. The extracorporeal circuit was well-tolerated hemodynamically. Treated animals had lower intracranial pressure compared with controls (at 24 h, 15 ± 3.1 vs. 22 ± 3.5 mm Hg, P = 0.006). Plasma ammonia in treated animals was lower compared with controls at 12 h (100 ± 29 vs. 244 ± 131 µmol, P = 0.026). Liver histological study showed decreased necrosis and increased regeneration activity in treated animals compared with controls. Treatment through an extracorporeal hepatocyte bioreactor attenuates brain edema and improves histological and functional parameters of the liver remnant of pigs with posthepatectomy liver failure.
authors.affiliation: Experimental Surgical Unit, 2nd Department of Surgery, Medical School, University of Athens, Aretaieion Hospital, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Arkadopoulos
authors.forename: Georgia
authors.initials: G
authors.lastname: Kostopanagiotou
authors.forename: Constantinos
authors.initials: C
authors.lastname: Nastos
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papoutsidakis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kalimeris
authors.forename: George
authors.initials: G
authors.lastname: Defterevos
authors.forename: Themis
authors.initials: T
authors.lastname: Kanna
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Polyzois
authors.forename: George
authors.initials: G
authors.lastname: Kampouroglou
authors.forename: Dimosthenis
authors.initials: D
authors.lastname: Kypriotis
authors.forename: Constantinos
authors.initials: C
authors.lastname: Costopanagiotou
authors.forename: Agathi
authors.initials: A
authors.lastname: Pafiti
authors.forename: Helen
authors.initials: H
authors.lastname: Tzanatos
authors.forename: Vassilios
authors.initials: V
authors.lastname: Smyrniotis
mesh_terms: D000818:Animals; D019149:Bioreactors; D004867:Equipment Design; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology*; D008099:Liver / Q000166:cytology / Q000473:pathology / Q000601:surgery; D017093:Liver Failure / Q000473:pathology / Q000628:therapy*; D008111:Liver Function Tests; D019164:Liver, Artificial; D013552:Swine