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.
Highlights
Liver transplantation (LT) is the only treatment proven to prolong survival in patients with acute liver failure (ALF), who fulfil criteria for poor prognosis, but LT remains a limited resource with alternative therapies being an unmet need [1]
Two APAP-Control Device’ (CD) pigs were excluded due to early achievement of ALF criteria at 12.5 and 13 h after onset of APAP dosing, more than 30% below the mean of 19.3 ± 1.8 expected for the Porcine model of acute liver failure (PALF) model
University College London-Liver Dialysis Device (UCL-LDD) resulted in a 67% reduced risk of ‘‘death’’ compared to CD
Summary
Liver transplantation (LT) is the only treatment proven to prolong survival in patients with acute liver failure (ALF), who fulfil criteria for poor prognosis, but LT remains a limited resource with alternative therapies being an unmet need [1].
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