Recent advances in MASLD genetics: Insights into disease mechanisms and the next frontiers in clinical application
Hepatology Communications,
Год журнала:
2025,
Номер
9(1)
Опубликована: Янв. 1, 2025
Metabolic
dysfunction–associated
steatotic
liver
disease
(MASLD)
is
the
most
common
chronic
in
world
and
a
growing
cause
of
liver-related
morbidity
mortality.
Yet,
at
same
time,
our
understanding
pathophysiology
genetic
underpinnings
this
increasingly
yet
heterogeneous
has
increased
dramatically
over
last
2
decades,
with
potential
to
lead
meaningful
clinical
interventions
for
patients.
We
have
now
seen
first
pharmacologic
therapy
approved
treatment
MASLD,
multiple
other
treatments
are
currently
under
investigation—including
gene-targeted
RNA
therapies
that
directly
extend
from
advances
MASLD
genetics.
Here
we
review
recent
genetics,
some
key
pathophysiologic
insights
human
genetics
provided,
ways
which
may
inform
practice
field
near
future.
Язык: Английский
Alcohol and Hepatocellular Carcinoma
Clinics in Liver Disease,
Год журнала:
2024,
Номер
28(4), С. 633 - 646
Опубликована: Июль 23, 2024
Язык: Английский
Reply: Polygenic risk score in cirrhosis: Does the etiology matter?
Hepatology Communications,
Год журнала:
2025,
Номер
9(2)
Опубликована: Янв. 15, 2025
Язык: Английский
Polygenic risk score in cirrhosis: Does the etiology matter?
Hepatology Communications,
Год журнала:
2025,
Номер
9(2)
Опубликована: Янв. 15, 2025
Язык: Английский
Alcohol-Associated Liver Disease and Risk Stratification for Hepatocellular Carcinoma: A Comprehensive Review
Jaeyoun Choi,
Hyun-seok Kim
Current Hepatology Reports,
Год журнала:
2025,
Номер
24(1)
Опубликована: Апрель 15, 2025
Язык: Английский
From detection to intervention, optimizing care for patients with alcohol use disorder and advanced hepatic fibrosis
Alcohol Clinical and Experimental Research,
Год журнала:
2024,
Номер
48(12), С. 2253 - 2255
Опубликована: Окт. 27, 2024
Nearly
half
of
the
world's
population
consumes
alcohol,
with
approximately
20%
engaging
in
binge
drinking
and
5%–10%
excessively
over
long
term
(Manthey
et
al.,
2019).
Alcohol
consumption
is
a
leading
cause
liver
disease
mortality
both
United
States
Europe,
contributing
to
significant
public
health
burden
(Karlsen
2022).
The
risk
developing
alcohol-associated
(ALD)
varies
widely
among
individuals,
influenced
by
factors
such
as
genetics
(Schwantes-An
2024;
Yuan
2024),
socioeconomic
status
(Askgaard
2021),
specific
patterns
(Aberg
2017).
Additionally,
stigma
surrounding
heavy
complicates
accurate
tracking
alcohol
intake,
underreporting
misdiagnosis
(Schomerus
Unlike
many
other
diseases,
ALD
often
diagnosed
late,
typically
after
serious
complications
from
portal
hypertension
or
advanced
fibrosis
have
developed
(Shah
progression
drinkers
heterogeneous;
while
some
individuals
develop
severe
problems
rapidly,
others
may
experience
slower
remain
relatively
unaffected
for
years
(Israelsen
2024).
Noninvasive
tests
(NITs)
play
crucial
role
identifying
high-risk
patients
who
require
intervention,
distinguishing
them
those
at
lower
Early
detection
through
NITs
focuses
on
two
critical
scenarios:
screening
at-risk
diagnosing
predicting
outcomes
Liver
fibrosis,
key
predictor
failure
asymptomatic
patients,
can
be
assessed
using
various
methods
These
include
elastography-based
tools
stiffness
measurement
(LSM)
blood-based
markers
fibrosis-4
test
(FIB-4)
While
LSM
provides
valuable
insights
into
stiffness,
its
availability
limited,
particularly
nonspecialist
settings,
which
restricts
use
routine
early
In
contrast,
biomarkers
FIB-4
offer
more
convenient
accessible
option
screening,
allowing
easier
implementation
healthcare
settings
Patients
excessive
(EAU)
disorder
(AUD)
represent
ALD,
primarily
due
their
significantly
elevated
damage.
Prolonged
lead
development
rendering
AUD
susceptible
diseases.
Our
recent
study
has
highlighted
urgency
this
issue,
demonstrating
that
one
five
admitted
treatment
exhibits
values
indicative
(Zuluaga
Screening
essential,
it
enables
identification
initial
stages,
timely
interventions
reduce
complications.
October
2024
issue
ACER,
Houston
al.
(2024)
examined
whether
EAU
high
scores
are
being
appropriately
referred
hepatology.
Analyzing
records
1131
large
system
between
2013
2023,
they
found
only
37%
316
active
were
hepatology
(Houston
alcohol-related
mental
issues
trauma
less
likely
receive
referrals,
hospitalizations
higher
comorbidity
Alarmingly,
nearly
63%
not
care
need
valuable,
but
effectiveness
depends
actions
taken
following
results.
Identifying
just
step;
essential
providers
implement
appropriate
follow-up
address
these
findings
effectively.
success
initiatives
relies
coordinated
approach
emphasizes
also
importance
clinical
responses.
This
includes
making
prompt
referrals
specialists,
comprehensive
management
plans,
implementing
targeted
tailored
each
patient's
needs.
Without
actions,
efforts
fail
translate
meaningful
improvements
patient
outcomes.
According
(2024),
despite
awareness
disease,
referral
rates
services
alarmingly
low.
trend
pronounced
trauma,
frequently
miss
out
evaluations
Several
contribute
concerning
issue.
First,
prioritize
immediate
needs
potential
issues,
especially
emergency
inpatient
settings.
acute
focus
psychiatric
physical
crises
overshadow
assessing
underlying
(Johnson
As
result,
overlooked,
missed
opportunities
referrals.
Second,
primary
unfamiliar
noninvasive
score
liver-related
risks
associated
knowledge
gap
result
an
underestimation
severity
recognize
necessity
specialized
care.
Third,
conditions
introduce
biases
(Ahad
2023).
Providers
might
unconsciously
view
having
urgent
medical
concerns,
diminishes
emphasis
conducting
screenings
disease.
present
clear
complications,
Finally,
systemic
fragmented
models
inadequate
communication
care,
health,
further
exacerbate
challenges
facilitating
(McGinty
&
Daumit,
2020;
Zuchowski
2015).
To
enhance
within
multifaceted
essential.
begins
increasing
education
training
emphasizing
pathophysiology
score.
Implementing
integrated
foster
collaboration
vital
(Winder
Such
facilitate
regular
ensuring
prioritized
standardized
protocols
assessments
during
visits
streamline
individuals.
Utilizing
electronic
flag
will
process
(Khan
Engaging
about
paramount.
Empowering
advocate
well-being
greater
involvement
encourage
seek
screenings.
Establishing
robust
results
specialty
improving
(Seyed-Nezhad
2021).
providers,
without
unnecessary
delays
(Sheehan
Furthermore,
continuous
quality
improvement
framework
monitor
processes
(Hill
2020).
By
collecting
analyzing
data
rates,
patterns,
outcomes,
identify
areas
inform
ongoing
policy
adjustments
sheds
light
improved
practices
fibrosis.
low
services,
research
underscores
integrating
gained
interventions,
enhanced
utilization
tools.
addressing
gaps
fostering
we
improve
AUD,
better
work
supported
part
U01AA026917,
UH3AA026903,
R01AA030312
NIH/NIAAA;
Department
Veterans
Affairs
Merit
Award
I01CX000361
I01BX006202;
Dean's
Scholar
Indiana
University
School
Medicine
(SL);
JR20/00016
RD21/0009/0004
Instituto
de
Salud
Carlos
III;
Centres
Recerca
Catalunya
2021-SGR-00945.
None.
Язык: Английский
Development of a Polygenic Risk Score for Metabolic Dysfunction-Associated Steatotic Liver Disease Prediction in UK Biobank
Genes,
Год журнала:
2024,
Номер
16(1), С. 33 - 33
Опубликована: Дек. 28, 2024
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
is
the
leading
cause
of
liver-related
morbidity
and
mortality.
Although
invasive
biopsy
remains
golden
standard
for
MASLD
diagnosis,
Magnetic
Resonance
Imaging-derived
Proton
Density
Fat
Fraction
(MRI-PDFF)
an
accurate,
non-invasive
method
assessment
treatment
response.
This
study
aimed
at
developing
a
Polygenic
Risk
Score
(PRS)
to
improve
MRI-PDFF
prediction
using
UK
Biobank
data
assess
individual's
genetic
liability
MASLD.
We
iteratively
sequestered
10%
samples
as
validation
set
split
rest
each
dataset
into
base
target
partitions,
containing
GWAS
summary
statistics
raw
genotype
data,
respectively.
PRSice2
was
deployed
derive
PRS
candidates.
Based
on
frequency
SNP
appearances
along
candidates,
we
generated
different
sets
according
variable
cutoffs.
By
applying
PRSs
set,
identified
optimal
which
then
applied
Greek
nonalcoholic
fatty
(NAFLD)
study.
Data
from
3553
participants
yielded
49
sets.
After
calculating
every
with
75
SNPs
selected
(incremental
R2
=
0.025,
p-value
0.00145).
Interestingly,
43
were
successfully
mapped
MASLD-related
known
genes.
The
could
predict
traits,
like
LDL
cholesterol
diastolic
blood
pressure
in
Biobank,
also
outcome
NAFLD
Our
findings
provide
strong
evidence
that
powerful
model
MASLD,
while
it
can
be
populations
ethnicity.
Язык: Английский
Alcohol‐induced pancreatitis and alcohol‐related liver disease: Two different phenotypes of alcohol‐related harm or related conditions?
Journal of Internal Medicine,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 14, 2024
It
is
well
known
that
overconsumption
of
alcohol
can
cause
tissue
injury
in
the
liver
and
pancreas,
apart
from
many
other
organs
such
as
heart,
brain,
peripheral
nervous
system.
has
also
been
recognized
less
than
5%
individuals
who
drink
excessively
will
develop
episodes
acute
pancreatitis
[1].
The
definition
heavy
drinking
beyond
scope
this
editorial,
obtaining
a
reliable
history
use
be
challenge.
pattern
lifetime
did
not
reveal
any
major
differences
among
patients
with
disorder
(AUD)
were
hospitalized
for
rehabilitation
(without
alcoholic
pancreatitis)
previously
diagnosed
alcohol-induced
(AIP)
[2].
In
study,
males
AIP
had
significantly
lower
total
amount
spirits
proportion
binge
those
AUD,
suggesting
idiosyncratic
etiology
study
Portugal,
lifestyle
eating
habits
seemed
to
impact
development
[3].
Patients
disease
(ALD)
higher
consumption
patients,
latter
group
reported
more
abundant
diet
past
A
Swedish
prospective
population-based
revealed
vegetable
but
fruit
might
prevent
non-gallstone-related
[4].
Thus,
may
influence
[2-4].
Although
knowledge
available
on
risk
ALD
based
threshold
values
consumption,
only
minority
drinkers
[5].
However,
incidence
both
shown
increase
increased
per
capita
general
population
[6].
present
issue
Journal
Internal
Medicine,
Dugic
et
al.
sixfold
compared
matched
controls
[7].
7%
experienced
prior
diagnosis
ALD,
ninefold
controls.
cumulative
hospitalization
ALP
was
2.7%
controls,
seems
very
low
suffer
AIP.
by
al.,
independent
factors
developing
younger
age,
male
sex,
diagnoses
obstructive
pulmonary
included
an
impressive
number
long
follow-up.
This
registry
good
quality
health
care
Sweden
socialized
medicine
system,
which
means
all
during
period
private
hospitals
have
inpatients.
it
big
strength
without
selection
bias.
As
registry-based
studies
relying
ICD-9
ICD-10
codes,
these
are
always
reliable.
authors
current
tried
validate
their
codes
200
pancreatitis,
positive
predictive
value
relatively
high
when
accounting
missing
data
(86%).
completely
clear
if
accuracy
presence
or
biliary
pancreatitis.
most
common
neighbouring
countries
gallstone-induced
[8].
acknowledge,
likely
some
Furthermore,
should
expected
scrutinization
medical
records,
information
about
managed
stop
available.
Similarly,
smoking
available,
used
chronic
(COPD)
marker
smoking.
COPD
found
predictor
in-line
previous
showing
increases
first
20
years
1969
1989,
before
detection
hepatitis
C,
suffered
C.
unclear
how
affected
results.
[8],
in-hospital
mortality
observed
incident
episode
comparators,
0.3%
versus
0.1%.
absolute
terms,
although
statistically
significant,
results
hardly
clinically
significant.
summary,
interest
probably,
despite
methodological
limitations,
published
so
far
relationship
between
congratulated
hard
work
thorough
statistical
analysis.
there
after
risk,
particularly
diagnosis,
low.
Only
2.8%
developed
established
diagnosis.
conceivable
prone
successful
stopping
due
"antabuse"
effect
usually
painful
concluded
remarkably
few
experience
vice
versa.
vast
majority
never
ALD.
two
phenotypes,
AIP,
different
genetic
risks
[9,
10].
author
declares
no
conflicts
interest.
Data
sharing
applicable
article
new
created
analyzed
study.
Язык: Английский