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

Autor: Giacomo Stanzani, Rajiv Jalan, P Leckie, Rosalind E. Jenkins, Daniel J. Antoine, H I K Alibhai, Luisa A. Baker, Christopher E. Goldring, Paola Giordano, Banwari Agarwal, Fausto Andreola, Carolina Palacios, Karla C. L. Lee, Nathan Davies, B. Kevin Park, Simon L. Priestnall, Yu-Mei Chang, Rajeshwar P. Mookerjee
Jazyk: angličtina
Rok vydání: 2015
Předmět:
HNA-2
irreversibly oxidised human non-mercaptalbumin-2

SIRS
systemic inflammatory response syndrome

Extracorporeal Circulation
ACLF
acute-on chronic liver failure

Swine
medicine.medical_treatment
DAMP
damage-associated molecular pattern

Control-CD
group treated with placebo
water and CD

RR
respiratory rate

IL-1ra
IL-1 receptor antagonist

INR
international normalised ratio

UCL-LDD
Liver transplantation
SVI
stroke volume index

Gastroenterology
TLR4
toll-like receptor 4

PaCO2
partial pressure of carbon dioxide in arterial blood

APAP-UCL-LDD
group treated with APAP and UCL-LDD

0302 clinical medicine
DNA
deoxyribonucleic acid

Endotoxin
HNA-1
reversibly oxidised human non-mercaptalbumin-1

Medicine
HMGB1 Protein
Liver injury
0303 health sciences
biology
HR
heart rate

Liver dialysis
Pinsp
inspiratory pressures

ELISA
enzyme-linked immunosorbent assay

MAP
mean arterial pressure

PaO2/FiO2
ratio of partial pressure of oxygen in arterial blood to percentage of oxygen in inspired gases

3. Good health
PCWP
pulmonary capillary wedge pressure

UCL-LDD
University College London-Liver Dialysis Device

ICP
intracranial pressure

030211 gastroenterology & hepatology
Female
APAP-CD
group treated with APAP and CD

LVSWI
left ventricular stroke work index

medicine.drug
Research Article
Signal Transduction
medicine.medical_specialty
SVRI
systemic vascular resistance index

HMGB1
high-mobility group box-1 protein

Serum albumin
APAP
acetaminophen

PALF
porcine model of acute liver failure

Lung injury
LT
liver transplantation

03 medical and health sciences
ALF
acute liver failure

Internal medicine
Hemofiltration
CD
Control Device

Animals
CI
cardiac index

Serum Albumin
030304 developmental biology
Acetaminophen
MARS
Molecular Adsorbent Recirculating System

Nalp3
nacht
leucine-rich repeat and pyrin domain-containing protein 3

Hepatology
ALP
alkaline phosphatase

business.industry
HAS
human serum albumin

AST
aspartate amino transferase

Albumin
Extracorporeal circulation
Liver Failure
Acute

medicine.disease
Toll-like receptor 4
CVP
central venous pressure

Liver
Artificial

Surgery
IL
interleukin

HMA
non-oxidised human mercaptalbumin

Endotoxins
PEEP
positive end expiratory pressure

PaO2
partial pressure of oxygen in arterial blood

biology.protein
RVSWI
right ventricular stroke work index

Sorption Detoxification
Extracorporeal liver assist device
business
NAPQI
N-acetyl-p-benzoquinone imine

Acute liver failure
Zdroj: Journal of Hepatology
ISSN: 1600-0641
0168-8278
Popis: 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.
Databáze: OpenAIRE