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2015 ; 35
(7
): 1877-85
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Mechanisms of fibrosis in acute liver failure
#MMPMID25388426
He Y
; Jin L
; Wang J
; Yan Z
; Chen T
; Zhao Y
Liver Int
2015[Jul]; 35
(7
): 1877-85
PMID25388426
show ga
BACKGROUND & AIMS: Acute liver failure (ALF) is a condition with high mortality
and morbidity. Fibrosis in chronic liver disease was extensively researched,
whereas fibrosis and underlying mechanism in acute liver failure remains unclear.
METHODS: Hepatitis B virus related ALF patients were recruited to investigate if
there was ongoing fibrosis by liver histology and liver stiffness
measurement(LSM) analysis as well as fibrosis markers assay. Sera HMGB1 were
kinetically detected in progression and remission stage of ALF. Hepatic stellate
cell(HSC) activation by HMGB1 was explored by testing mRNA and protein level of
?-SMA and collagen 1a1 by using qPCR and western blot. Autophagy induction by
HMGB1 was explored by LC3-II conversion, autophagy flux and fluorescence.
RESULTS: Firstly, ongoing fibrosis in progression stage of ALF was confirmed by
histological analysis, LS measurement as well as fibrosis markers detection. HSC
activation and autophagy induction in explanted liver tissue also revealed. Next,
kinetic monitoring sera HMGB1 revealed elevated HMGB1 in progression stage of ALF
vs HBsAg carrier, and drop back to base level in remission stage. Thirdly, rHMGB1
dose dependently activated HSCs, as indicated by increased mRNA and proteins
level in ?-SMA and collagen 1a1. Moreover, autophagy was induced in HSC treated
with rHMGB1, as illustrated by increased LC3 lipidation, elevated autophagy flux
and GFP-LC3 puncta. CONCLUSIONS: Acute liver failure is accompanied by ongoing
fibrosis, HSC activation and autophagy induction. Increased HMGB1 activates HSC
via autophagy induction. Those findings integrate HMGB1, HSCs activation,
autophagy into a common framework that underlies the fibrosis in ALF.
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