medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 10, 2024
Abstract
Alcohol-related
liver
disease
(ALD)
is
a
major
cause
of
mortality
and
disability
adjusted
life
years.
It
not
fully
understood
why
small
proportion
patients
develop
progressive
forms
ALD
(e.g.
fibrosis,
cirrhosis).
Differences
in
the
metabolic
processes
could
be
behind
individual
progression
ALD.
Our
aim
was
to
examine
differences
serum
metabolome
between
with
non-progressive
an
early
form
The
study
had
three
groups:
(alcohol-related
steatohepatitis
or
early-stage
n=50),
(simple
steatosis,
n=50)
healthy
controls
(n=32).
Both
groups
took
part
voluntary
alcohol
rehabilitation
program.
A
non-targeted
metabolomics
analysis
targeted
short
chain
fatty
acids
done
samples
taken
on
day
admission.
We
found
111
significantly
(p<0.0005)
altered
identified
metabolites
groups.
main
finding
that
levels
glycine
conjugated
bile
acids,
glutamic
acid,
7-methylguanine
several
phosphatidylcholines
were
elevated
group
comparison
both
controls.
Glycine
acid
also
positively
correlated
increased
aspartate
aminotransferase,
alanine
gamma-glutamyl
transferase,
cell
death
biomarker
M65,
stiffness.
results
indicate
enterohepatic
cycle
as
well
lipid
energy
metabolism
are
These
target
for
preventing
Alimentary Pharmacology & Therapeutics,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 31, 2025
Glucagon-like
peptide-1
receptor
agonists
(GLP-1RAs)
have
shown
promise
in
reducing
alcohol
consumption,
but
their
impact
on
clinical
outcomes
patients
with
use
disorder
(AUD)
remains
unclear.
We
investigated
the
association
between
GLP-1RAs
and
development
progression
of
alcohol-related
liver
disease
(ArLD)
AUD.
Using
TriNetX
Research
Network,
we
conducted
two
retrospective
cohort
studies
comparing
versus
dipeptidyl
peptidase-4
inhibitors
(DPP-4is)
type
2
diabetes.
The
first
included
AUD
without
ArLD
(n
=
7132
after
propensity
score
matching),
while
second
comprised
established
1896
matching).
Primary
were
incident
hepatic
decompensation
cohort.
In
(median
follow-up:
63.2
months),
GLP-1RA
users
showed
significantly
lower
risks
developing
compared
to
DPP-4i
(incidence
rate:
6.0
vs.
8.7
per
1000
person-years;
HR:
0.62,
95%
CI:
0.44-0.87,
p
0.006).
also
associated
reduced
all-cause
mortality
(HR:
0.53,
<
0.001).
28.2
demonstrated
39.5
51.4
0.66,
0.51-0.85,
0.001)
users.
progressing
AUD,
suggesting
potential
therapeutic
benefits
this
population.
Liver International,
Год журнала:
2025,
Номер
45(3)
Опубликована: Фев. 10, 2025
The
burden
of
cirrhosis
and
other
chronic
liver
diseases
has
changed
in
recent
years
due
to
shifts
the
contributing
aetiologies.
We
estimated
diseases,
including
etiological
regional
differences,
across
204
countries
territories
from
2010
2021.
analysed
temporal
trends
utilising
data
Global
Burden
Disease
Study
annual
frequencies
age-standardised
rates
(ASRs)
incident
cases,
deaths
disability-adjusted
life-years
(DALYs)
by
sex,
country,
World
Health
Organisation
region
its
In
2021,
there
were
an
58
417
006
1
425
142
46
777
DALYs
related
diseases.
From
was
a
rise
incidence
(ASIRs)
(APC:
+0.35%)
but
death
(ASDRs)
-1.74%)
(ASDALYs)
-1.85%)
declined.
Cirrhosis
metabolic
dysfunction-associated
steatohepatitis
(MASH)
contributed
48
310
981
cases
2021
largely
responsible
for
overall
increase
ASIRs
MASH
only
aetiology
with
ASIR
+0.86%).
Age-standardised
all
aetiologies
declined
during
study
period.
increased
Americas,
unlike
world
regions
where
they
or
remained
stable.
Age-adjusted
are
declining.
However,
age-adjusted
is
increasing,
driven
increases
MASH.
Hepatology forum/Hepatology forum (Online),
Год журнала:
2025,
Номер
unknown, С. 77 - 86
Опубликована: Янв. 1, 2025
Alcoholic
liver
disease(ALD)
is
considered
as
a
growing
public
health
issue
with
universally
increasing
disease
burden.
Various
genetic
and
environmental
factors
play
role
in
its
etiology.
ALD
recently
has
become
the
major
indication
for
Liver
Transplantation
(LT).
Most
LT
programs
select
their
candidates
by
adhering
to
six
months
of
alcohol
abstinence
policy.
Nevertheless,
early
transplantation
(ELT)
subject
research,
both
Europe
United
States,
an
effective
lifesaving
option
among
highly
selected
severe
alcohol-associated
hepatitis
(SAH)
patients.
ELT
promising
way
management
ALD,
perhaps
changing
clinical
practice
carefully
patient
groups.
Gut,
Год журнала:
2025,
Номер
unknown, С. gutjnl - 334412
Опубликована: Апрель 8, 2025
Background
Gut-liver
crosstalk
plays
an
important
role
in
alcohol-associated
liver
disease
(ALD)
pathogenesis;
but
underlying
mechanisms
remain
obscure.
Objective
We
examined
the
regulation
of
intestinal
and
intrahepatic
CD8
+
T
lymphocytes
their
contribution
to
ALD.
Design
ALD
patients
were
recruited
for
evaluation
cells.
Single-cell
RNA
sequencing
(scRNA
seq)
was
performed
analyse
peripheral
cells
Wildtype,
CD8-specific
Bcl2
transgenic
(
Cd8
Bcl-2
),
−/−
mice
subjected
chronic-plus-binge
ethanol
feeding.
Results
In
patients,
duodenal
selectively
reduced
negatively
correlated
with
injury
bacterial
translocation
markers,
while
markedly
increased.
ScRNA
seq
analysis
patient
livers
revealed
several
populations
expressing
activation
survival
genes
(eg,
).
Transcriptomics
functional
studies
a
key
prosurvival
BCL2
this
opposite
Mechanistically,
feeding
specifically
duodenum
where
levels
are
high.
Inducing
reversed
ethanol-induced
loss
cells,
improved
gut
barrier
function
ameliorated
ALD,
deficiency
linked
enhanced
neutrophil
macrophage
infiltration
liver,
exacerbating
mice.
Conclusions
is
associated
elevation
which
aggravates
ameliorates
respectively.
Restoration
functions
may
represent
novel
therapeutic
strategy
patients.
