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2015 ; 63
(3
): 634-42
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Extracorporeal liver assist device to exchange albumin and remove endotoxin in
acute liver failure: Results of a pivotal pre-clinical study
#MMPMID25937432
Lee KC
; Baker LA
; Stanzani G
; Alibhai H
; Chang YM
; Jimenez Palacios C
; Leckie PJ
; Giordano P
; Priestnall SL
; Antoine DJ
; Jenkins RE
; Goldring CE
; Park BK
; Andreola F
; Agarwal B
; Mookerjee RP
; Davies NA
; Jalan R
J Hepatol
2015[Sep]; 63
(3
): 634-42
PMID25937432
show ga
BACKGROUND & AIMS: In 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. METHODS: Pigs 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. RESULTS: The
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. CONCLUSIONS: The survival benefit and lack of adverse effects
would support clinical trials of University College London-Liver Dialysis Device
in acute liver failure patients.