Development of a porcine model of post-hepatectomy liver failure.

BACKGROUND: The aim of this study was to develop a porcine model of post-operative liver failure (POLF) that could accurately reproduce all the neurological and metabolic parameters of the corresponding clinical syndrome that may develop after extensive liver resections. METHODS: In our model, we induced POLF by combining extended left hepatectomy and ischemia of the small liver remnant of 150 min duration. Subsequently, the remnant liver parenchyma was reperfused and the animals were closely monitored for 24 h. MATERIALS: Twelve Landrace pigs (weight 25-30 kg) were randomly assigned in two groups; eight of them constituted the experimental group, in which POLF was induced (POLF group, n = 8), whereas the rest of them (n = 4) were included in the control group (sham laparotomy without establishment of POLF). RESULTS (MEANS ± SD): All POLF animals gradually developed neurological and biochemical signs of liver failure including, among many other parameters, elevated intracranial pressure (24.00 ± 4.69 versus 10.17 ± 0.75, P = 0.004) and ammonia levels (633.00 ± 252.21 versus 51.50 ± 9.49, P = 0.004) compared with controls. Histopathologic evaluation of the liver at the end of the experiment demonstrated diffuse coagulative necrosis and severe architectural distortion of the hepatic parenchyma in all POLF animals. CONCLUSION: Our surgical technique creates a reproducible porcine model of POLF which can be used to study the pathophysiology and possible therapeutic interventions in this serious complication of extensive hepatectomies.

Reversal of experimental posthepatectomy liver failure in pigs: a new application of hepatocyte bioreactors.

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.