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.
Obesity Facts,
Год журнала:
2024,
Номер
17(4), С. 374 - 444
Опубликована: Янв. 1, 2024
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD),
previously
termed
non-alcoholic
fatty
(NAFLD),
is
defined
as
(SLD)
in
the
presence
of
one
or
more
cardiometabolic
risk
factor(s)
and
absence
harmful
alcohol
intake.
The
spectrum
MASLD
includes
steatosis,
metabolic
steatohepatitis
(MASH,
NASH),
fibrosis,
cirrhosis
MASH-related
hepatocellular
carcinoma
(HCC).
This
joint
EASL-EASD-EASO
guideline
provides
an
update
on
definitions,
prevention,
screening,
diagnosis
treatment
for
MASLD.
Case-finding
strategies
with
using
non-invasive
tests,
should
be
applied
individuals
factors,
abnormal
enzymes,
and/or
radiological
signs
hepatic
particularly
type
2
diabetes
(T2D)
obesity
additional
factor(s).
A
stepwise
approach
blood-based
scores
(such
FIB-4)
and,
sequentially,
imaging
techniques
transient
elastography)
suitable
to
rule-out/in
advanced
which
predictive
liver-related
outcomes.
In
adults
MASLD,
lifestyle
modification
-
including
weight
loss,
dietary
changes,
physical
exercise
discouraging
consumption
well
optimal
management
comorbidities
use
incretin-based
therapies
(e.g.
semaglutide,
tirzepatide)
T2D
obesity,
if
indicated
advised.
Bariatric
surgery
also
option
obesity.
If
locally
approved
dependent
label,
non-cirrhotic
MASH
significant
fibrosis
(stage
≥2)
considered
a
MASH-targeted
resmetirom,
demonstrated
histological
effectiveness
acceptable
safety
tolerability
profile.
No
pharmacotherapy
can
currently
recommended
cirrhotic
stage.
Management
adaptations
drugs,
nutritional
counselling,
surveillance
portal
hypertension
HCC,
transplantation
decompensated
cirrhosis.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Май 10, 2024
Abstract
Lanifibranor,
a
pan-PPAR
agonist,
improves
liver
histology
in
patients
with
metabolic
dysfunction-associated
steatohepatitis
(MASH),
who
have
poor
cardiometabolic
health
(CMH)
and
cardiovascular
events
as
major
mortality
cause.
NATIVE
trial
secondary
exploratory
outcomes
(ClinicalTrials.gov
NCT03008070)
were
analyzed
for
the
effect
of
lanifibranor
on
IR,
lipid
glucose
metabolism,
systemic
inflammation,
blood
pressure
(BP),
hepatic
steatosis
(imaging
histological
grading)
all
original
analysis.
With
lanifibranor,
triglycerides,
HDL-C,
apolipoproteins,
insulin,
HOMA-IR,
HbA1c,
fasting
(FG),
hs-CRP,
ferritin,
diastolic
BP
improved
significantly,
independent
diabetes
status:
most
prediabetes
returned
to
normal
FG
levels.
Significant
adiponectin
increases
correlated
CMH
marker
improvement;
had
an
average
weight
gain
2.5
kg,
49%
gaining
≥2.5%
weight.
Therapeutic
benefits
similar
regardless
change.
Here,
we
show
that
effects
MASH
are
accompanied
improvement,
indicative
potential
clinical
benefits.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(4), С. 1778 - 1778
Опубликована: Фев. 19, 2025
In
recent
years,
“metabolic
dysfunction-associated
steatotic
liver
disease”
(MASLD)
has
been
proposed
to
better
connect
disease
metabolic
dysfunction,
which
is
the
most
common
chronic
worldwide.
MASLD
affects
more
than
30%
of
individuals
globally,
and
it
diagnosed
by
combination
hepatic
steatosis
obesity,
type
2
diabetes,
or
two
risk
factors.
begins
with
buildup
extra
fat,
often
greater
5%,
within
liver,
causing
hepatocytes
become
stressed.
This
can
proceed
a
severe
form,
steatohepatitis
(MASH),
in
20–30%
people,
where
inflammation
causes
tissue
fibrosis,
limits
blood
flow
over
time.
As
fibrosis
worsens,
MASH
may
lead
cirrhosis,
failure,
even
cancer.
While
pathophysiology
not
fully
known,
current
“multiple-hits”
concept
proposes
that
dietary
lifestyle
factors,
genetic
epigenetic
factors
contribute
elevated
oxidative
stress
inflammation,
fibrosis.
review
article
provides
an
overview
pathogenesis
evaluates
existing
therapies
as
well
pharmacological
drugs
are
currently
being
studied
clinical
trials
for
MASH.
Biomolecules,
Год журнала:
2023,
Номер
13(8), С. 1264 - 1264
Опубликована: Авг. 18, 2023
The
number
of
patients
with
nonalcoholic
fatty
liver
disease
(NAFLD)/nonalcoholic
steatohepatitis
(NASH)
is
increasing
globally
and
raising
serious
concerns
regarding
the
medical
economic
burden
incurred
for
their
treatment.
progression
NASH
to
more
severe
conditions
such
as
cirrhosis
hepatocellular
carcinoma
requires
transplantation
avoid
death.
Therefore,
therapeutic
intervention
required
in
stage,
although
no
drugs
are
currently
available
this.
Several
anti-NASH
candidate
have
been
developed
that
enable
treatment
via
modulation
distinct
signaling
cascades
include
a
series
targeting
peroxisome
proliferator-activated
receptor
(PPAR)
subtypes
(PPARα/δ/γ)
considered
be
attractive
because
they
can
regulate
both
systemic
lipid
metabolism
inflammation.
Multiple
PPAR
dual/pan
agonists
but
only
few
them
evaluated
clinical
trials
NAFLD/NASH.
Herein,
we
review
current
trial
status
future
prospects
PPAR-targeted
treating
In
addition,
summarize
our
recent
findings
on
binding
modes
potencies/efficacies
several
estimate
potentials
against
NASH.
Considering
development
numerous
has
abandoned
side
effects,
also
propose
repositioning
already
approved,
safety-proven
