Hepatology,
Journal Year:
2018,
Volume and Issue:
68(3), P. 1163 - 1173
Published: March 31, 2018
Biliary
atresia
(BA)
is
a
fibroinflammatory
disease
of
the
intrahepatic
and
extrahepatic
biliary
tree.
Surgical
hepatic
portoenterostomy
(HPE)
may
restore
bile
drainage,
but
progression
results
in
complications
portal
hypertension
advanced
cirrhosis
most
children.
Recognizing
that
further
progress
field
unlikely
without
better
understanding
underlying
cause(s)
pathogenesis
disease,
National
Institutes
Diabetes
Digestive
Kidney
Diseases
(NIDDK)
sponsored
research
workshop
focused
on
innovative
promising
approaches
identifying
future
areas
research.
Investigators
discussed
recent
advances
using
gestational
ultrasound
newborn
BA
screening
with
serum
direct
(conjugated)
bilirubin
support
prenatal
onset
injury.
Experimental
human
studies
implicate
toxic
properties
environmental
toxins
(e.g.,
biliatresone)
viruses
cytomegalovirus)
to
system.
Among
host
factors,
sequence
variants
genes
related
development
ciliopathies,
notable
lack
cholangiocyte
glycocalyx
submucosal
collagen
bundles
neonatal
ducts,
an
innate
proinflammatory
bias
immune
system
contribute
increased
susceptibility
damage
obstruction
following
epithelial
These
form
foundation
for
agenda
factor(s)
cause
BA,
potential
use
population
screening,
mechanisms
prominent
fibrosis
young
infants,
determinations
clinical
surrogates
progression,
design
trials
target
subgroups
patients
initial
drainage
HPE.
(Hepatology
2018;
00:000-000).
Free Radical Biology and Medicine,
Journal Year:
2020,
Volume and Issue:
152, P. 116 - 141
Published: March 8, 2020
Nonalcoholic
fatty
liver
disease
(NAFLD)
has
emerged
as
the
most
common
chronic
worldwide
and
is
strongly
associated
with
presence
of
oxidative
stress.
Disturbances
in
lipid
metabolism
lead
to
hepatic
accumulation,
which
affects
different
reactive
oxygen
species
(ROS)
generators,
including
mitochondria,
endoplasmic
reticulum,
NADPH
oxidase.
Mitochondrial
function
adapts
NAFLD
mainly
through
downregulation
electron
transport
chain
(ETC)
preserved
or
enhanced
capacity
mitochondrial
acid
oxidation,
stimulates
ROS
overproduction
within
ETC
components
upstream
cytochrome
c
However,
non-ETC
sources
ROS,
particular,
β-oxidation,
appear
produce
more
metabolic
diseases.
Endoplasmic
reticulum
stress
oxidase
alterations
are
also
NAFLD,
but
degree
their
contribution
remains
unclear.
Increased
generation
induces
changes
insulin
sensitivity
expression
activity
key
enzymes
involved
metabolism.
Moreover,
interaction
between
redox
signaling
innate
immune
forms
a
complex
network
that
regulates
inflammatory
responses.
Based
on
mechanistic
view
described
above,
this
review
summarizes
mechanisms
may
account
for
excessive
production
potential
roles
drive
progression,
therapeutic
interventions
related
Gut,
Journal Year:
2017,
Volume and Issue:
67(10), P. 1881 - 1891
Published: Aug. 3, 2017
Objective
Bile
acids
are
regulators
of
lipid
and
glucose
metabolism,
modulate
inflammation
in
the
liver
other
tissues.
Primary
bile
such
as
cholic
acid
chenodeoxycholic
(CDCA)
produced
liver,
converted
into
secondary
deoxycholic
(DCA)
lithocholic
by
gut
microbiota.
Here
we
investigated
possible
roles
non-alcoholic
fatty
disease
(NAFLD)
pathogenesis
impact
microbiome
on
signalling
NAFLD.
Design
Serum
levels
fibroblast
growth
factor
19
(FGF19),
gene
expression
profiles
compositions
were
determined
patients
with
NAFLD,
high-fat
diet-fed
rats
their
controls.
Results
concentrations
primary
increased
In
per
cent,
farnesoid
X
receptor
(FXR)
antagonistic
DCA
was
increased,
while
agonistic
CDCA
decreased
Increased
mRNA
for
cytochrome
P450
7A1,
Na
+
-taurocholate
cotransporting
polypeptide
paraoxonase
1,
no
change
small
heterodimer
partner
salt
export
pump,
reduced
serum
FGF19
evidence
impaired
FXR
4
(FGFR4)-mediated
Taurine
glycine
metabolising
bacteria
reflecting
production.
Similar
changes
observed
rats.
Conclusions
The
profile,
hepatic
pattern
composition
consistently
support
an
elevated
production
proportion
explains,
at
least
part,
suppression
FXR-mediated
FGFR4-mediated
signalling.
Our
study
suggests
that
future
NAFLD
intervention
may
target
components
signalling,
including
converting
microbiome.
