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.

Pancreatic injury after major hepatectomy: a study in a porcine model

“…All animals subjected to hepatectomy manifested acute liver injury and postoperative liver dysfunction, as previously described in this experimental model [20,21]. Portal pressure was normal during the ischemic period while portal blood was directed through the anastomosis to the inferior vena cava.…”

“…This experimental model was used because it leads to postoperative oxidative stress and hepatic injury similar to that observed in the clinical setting following major hepatectomies. The protocol induced 150 min of liver ischemia because pilot experiments demonstrated that less ischemic time in combination with a portacaval anastomosis is not sufficient to produce acute liver injury, whereas a longer ischemic period leads to death before the completion of 24 h (unpublished data) [20,21]. The use of a portacaval shunt prevents bowel congestion.…”

Artificial Organs 2011: A Year in Review

“…Nikolaos Arkadopoulos et al. (94) of Aretaieion Hospital, Athens, Greece evaluated the effectiveness of a hepatocyte bioreactor in the treatment of experimental post‐hepatectomy liver failure. The experimental model included a combination of a side‐to‐side portacaval shunt, occlusion of the hepatoduodenal ligament for 150 min, 70% hepatectomy, and reperfusion.…”

Laparoscopic left hepatectomy in swine: a safe and feasible technique

“…Laparoscopic techniques for left hepatectomy have been widely described for humans [1,3,5,12,17,24,29]. Additionally, the ability to perform an anatomically reproducible hepatic resection in a large animal model could promote the investigation of liver surgery [5,18,23,26], transplantation [19,22], and regeneration [2,6,13,15,16,20,26,27] for medical research and experimental studies.…”