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2017 ; 2017
(ä): 5928078
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HMGB1 and Extracellular Histones Significantly Contribute to Systemic
Inflammation and Multiple Organ Failure in Acute Liver Failure
#MMPMID28694564
Yang R
; Zou X
; Tenhunen J
; Tønnessen TI
Mediators Inflamm
2017[]; 2017
(ä): 5928078
PMID28694564
show ga
Acute liver failure (ALF) is the culmination of severe liver cell injury from a
variety of causes. ALF occurs when the extent of hepatocyte death exceeds the
hepatic regenerative capacity. ALF has a high mortality that is associated with
multiple organ failure (MOF) and sepsis; however, the underlying mechanisms are
still not clear. Emerging evidence shows that ALF patients/animals have high
concentrations of circulating HMGB1, which can contribute to multiple organ
injuries and mediate gut bacterial translocation (BT). BT triggers/induces
systemic inflammatory responses syndrome (SIRS), which can lead to MOF in ALF.
Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration
in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an
important factor that links BT and systemic inflammation in ALF. ALF
patients/animals also have high levels of circulating histones, which might be
the major mediators of systemic inflammation in patients with ALF. Extracellular
histones kill endothelial cells and elicit immunostimulatory effect to induce
multiple organ injuries. Neutralization of histones can attenuate acute liver,
lung, and brain injuries. In conclusion, HMGB1 and histones play a significant
role in inducing systemic inflammation and MOF in ALF.