European Journal of Clinical Investigation,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 29, 2024
Abstract
Background
4‐methylpyrazole
(4MP,
fomepizole)
is
a
competitive
inhibitor
of
alcohol
dehydrogenase
(ADH)
preventing
the
metabolism
ethylene
glycol
and
methanol,
respectively,
into
their
toxic
metabolites.
4MP
seems
also
to
possess
potential
in
treatment
intoxication
from
other
substance,
for
example,
acetaminophen,
modulate
JNK‐dependent
signalling.
Here,
we
determined
if
with
once
weekly
affects
development
diet‐induced
non‐obese
metabolic
dysfunction‐associated
steatotic
liver
disease
(MASLD)
C57BL/6
mice.
Methods
Male
mice
(6–8
weeks
old,
n
=
7‐8/group)
were
pair‐fed
either
liquid
control
diet
(C)
or
sucrose‐,
fat‐
cholesterol‐rich
(SFC)
8
while
being
concomitantly
treated
(50
mg/kg
bw
i.p.)
vehicle
week.
Liver
damage,
inflammatory
markers
glucose
tolerance
assessed.
Moreover,
endotoxin‐challenged
J774A.1
cells
pretreated
4MP,
pro‐inflammatory
Results
The
concomitant
SFC‐fed
attenuated
increase
JNK
phosphorylation
like
IFNγ,
IL‐6
3‐nitrotyrosine
protein
adducts
tissue
found
vehicle‐treated
mice,
not
affecting
impairments
portal
endotoxin
levels.
pretreatment
endotoxin‐stimulated
significantly
increases
mediators
Mcp1
.
Conclusions
Taken
together,
our
results
suggest
that
attenuates
activation
dampens
MASLD
Journal of Clinical Gastroenterology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 31, 2025
Metabolic
dysfunction-associated
steatohepatitis
(MASH)
has
become
the
dominant
cause
of
liver
disease
in
United
States.
With
growing
burden
this
gastroenterology
practices,
identification
and
treatment
those
at
risk
developing
adverse
outcomes
(cirrhosis,
hepatocellular
carcinoma,
or
liver-related
death)
urgent.
In
recent
years,
development
noninvasive
tests
(NITs)
to
identify
“at-risk
MASH”
patients
have
provided
cost-effective
algorithms
these
patients.
Although
historically
been
limited
lifestyle
modification,
FDA
approval
resmetirom
for
noncirrhosis
MASH
with
stages
2
3
fibrosis
a
new
opportunity
States
provide
novel
options.
Other
new
effective
regimens
are
on
horizon.
Given
that
hepatology
practices
heavily
rely
advanced
practice
providers
(APPs)
manage
MASLD,
APP
Committee
Global
NASH/MASH
Council
curated
essentials
day-to-day
management
our
busy
gastrohepatology
their
colleagues.
The
goal
document
is
equip
mobilize
more
GI
requisite
competencies
at-risk
MASH,
given
rapidly
evolving
landscape.
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
management
guidelines
have
been
published
worldwide;
we
aimed
to
summarize,
categorize
and
compare
their
lifestyle
intervention
recommendations.
International Journal of Translational Medicine,
Год журнала:
2025,
Номер
5(1), С. 7 - 7
Опубликована: Янв. 17, 2025
Metabolic
dysfunction-associated
steatohepatitis
(MASH)
is
rapidly
becoming
a
leading
cause
of
hepatocellular
carcinoma
and
end-stage
liver
transplantation.
Characterized
by
hepatic
steatosis,
lobular
inflammation,
hepatocyte
ballooning,
there
dire
need
to
develop
therapeutic
strategies
mitigate
MASH
alongside
the
subsequent
fibrosis
cirrhosis.
For
years,
development
for
treatment
had
been
considered
graveyard,
with
various
pharmacotherapies
failing
achieve
clinical
efficacy.
However,
recent
Food
Drug
Administration
(FDA)
approval
Madrigal
Pharmaceuticals’
Resmetirom
in
United
States
provides
positive
step
collective
effort
eradicate
MASH.
Granted,
much
about
Resmetirom’s
long-term
efficacy
safety
still
be
determined
multi-factorial
nature
pathogenesis,
continuing
evaluate
alternative
options
remains
best
interest
field.
Currently,
therapeutics
previously
approved
other
ailments,
novel
developed
specifically
MASH,
are
being
evaluated
late-phase
trials.
considering
complex
disease
varying
outcomes
assess
efficacy,
achieving
regulatory
as
continues
rigorous
endeavor.
In
this
review,
we
summarize
notable
mechanistic
backgrounds
having
achieved,
or
actively
undergoing,
trials
offer
our
perspectives
on
anti-MASH
development.
Journal of Clinical Medicine,
Год журнала:
2025,
Номер
14(4), С. 1042 - 1042
Опубликована: Фев. 7, 2025
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD),
a
progressive
frequently
associated
with
metabolic
disorders
such
as
type
2
diabetes
mellitus
(T2DM)
and
obesity,
has
the
potential
to
progress
symptomatically
cirrhosis
and,
in
some
cases,
hepatocellular
carcinoma.
Hence,
an
urgent
need
arises
identify
approve
new
therapeutic
options
improve
patient
outcomes.
Research
efforts
have
focused
on
either
developing
dedicated
molecules
or
repurposing
drugs
already
approved
for
other
conditions,
diseases.
Among
latter,
antidiabetic
anti-obesity
agents
received
most
extensive
attention,
pivotal
trial
results
anticipated
shortly.
However,
primary
focus
underlying
successful
regulatory
approvals
is
demonstrating
substantial
efficacy
improving
fibrosis
preventing
ameliorating
cirrhosis,
key
advanced
outcomes
within
MASLD
progression.
Besides
steatosis,
ideal
candidate
should
reduce
inflammation
effectively.
Although
shown
promise
lowering
MASLD-related
parameters,
evidence
of
their
impact
remains
limited.
This
review
aims
evaluate
whether
can
be
safely
effectively
used
patients
T2DM.
Our
paper
discusses
closest
approval
expectation
that
they
address
unmet
needs
this
increasingly
prevalent
disease.
