Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study

Abstract

Background & AimsIn acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure.MethodsPigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n = 9); Acetaminophen plus Control Device (n = 7); and Control plus Control Device (n = 4). Device treatment was initiated two h after onset of irreversible acute liver failure.ResultsThe Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio = 0.33, p = 0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p = 0.046); 54% reduction in overall severity of endotoxaemia (p = 0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen.ConclusionsThe survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients.

Current Evidence for Extracorporeal Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure

“…29,30 Further research into other functional cell sources (genetically modified liver cell lines, humanized pig cells, and hepatocyte spheroids) is ongoing. 45,46 Future studies will likely have to weigh the added levels of complexity and expense compared with purely detoxifying systems, such as HVP.…”

Serum Procalcitonin Correlates with Renal Function in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure

“…Systemic inflammation and immune system dysregulation are thought to integrate with the main physiopathological pathway involved in the natural history of HBV-ACLF [14]. Moreover, endotoxemia contributes to the activation of the innate immune system in liver failure [20]. This may explain the increase in serum PCT levels following endotoxemia and activation of the immune system in HBV-ACLF, in which serum LPS induces proinflammatory cytokines that stimulate the release of PCT, which in turn triggers the production of cytokines and causes a positive loop between PCT secretion and activation of the immune system [21].…”

Liver resection for cancer: New developments in prediction, prevention and management of postresectional liver failure

“…In addition, extracorporeal bio-artificial liver devices fulfil functions of the liver (including synthetic and immunological) by separation and passage of blood plasma through a reactor containing layers of animal or human hepatocytes [171]. The recently developed University College London-Liver Dialysis Device extracts albumin by hemofiltration and removes certain endotoxins by haemoperfusion, in combination with human albumin infusion [172]. Unfortunately, although the latter two devices show survival benefits, they have thus far been tested only in a pre-clinical setting.…”