Frontiers in Immunology,
Год журнала:
2021,
Номер
11
Опубликована: Фев. 5, 2021
Background
and
Aims
Patients
with
cirrhosis
acute-on-chronic
liver
failure
(ACLF)
have
immunosuppression,
indicated
by
an
increase
in
circulating
immune-deficient
monocytes.
The
aim
of
this
study
was
to
investigate
simultaneously
the
major
blood-immune
cell
subsets
these
patients.
Material
Methods
Blood
taken
from
67
patients
decompensated
(including
35
critically
ill
ACLF
intensive
care
unit),
12
healthy
subjects,
assigned
either
measurements
clinical
blood
counts
microarray
(genomewide)
analysis
RNA
expression
whole-blood;
neutrophils;
or
assessment
neutrophil
antimicrobial
functions.
Results
Several
features
were
found
not
those
without
ACLF.
Indeed,
count
showed
that
characterized
leukocytosis,
neutrophilia,
lymphopenia.
Using
CIBERSORT
method
deconvolute
whole-blood
RNA-expression
data,
revealed
hallmark
association
neutrophilia
increased
proportions
macrophages
M0-like
monocytes
decreased
memory
lymphocytes
(of
B-cell,
CD4
T-cell
lineages),
CD8
T
cells
natural
killer
cells.
Microarray
neutrophils
had
a
unique
phenotype
including
induction
glycolysis
granule
genes,
downregulation
cell-migration
cell-cycle
genes.
Moreover,
defective
production
superoxide
anion.
Conclusions
Genomic
that,
among
cirrhosis,
dysregulation
immune
cells,
increases
(that
phenotype)
monocytes,
depletion
several
lymphocyte
lymphocytes).
All
alterations,
along
anion
production,
may
contribute
immunosuppression
ACLF,
suggesting
targets
for
future
therapies.
Journal of Hepatology,
Год журнала:
2020,
Номер
74(3), С. 670 - 685
Опубликована: Дек. 7, 2020
Acute
decompensation
(AD)
of
cirrhosis
is
defined
by
the
development
ascites,
hepatic
encephalopathy
and/or
variceal
bleeding.
Ascites
traditionally
attributed
to
splanchnic
arterial
vasodilation
and
left
ventricular
dysfunction,
hyperammonaemia,
haemorrhage
portal
hypertension.
Recent
large-scale
European
observational
studies
have
shown
that
systemic
inflammation
a
hallmark
AD.
Here
we
present
working
hypothesis,
suggesting
through
an
impairment
functions
one
or
more
major
organ
systems
may
be
common
theme
act
synergistically
with
traditional
mechanisms
involved
in
Systemic
impair
system
function
which
are
not
mutually
exclusive.
The
first
mechanism
nitric
oxide-mediated
accentuation
preexisting
vasodilation,
resulting
overactivation
endogenous
vasoconstrictor
elicit
intense
vasoconstriction
hypoperfusion
certain
vascular
beds,
particular
renal
circulation.
Second,
cause
immune-mediated
tissue
damage,
process
called
immunopathology.
Finally,
induce
important
metabolic
changes.
Indeed,
inflammatory
responses
energetically
expensive
processes,
requiring
reallocation
nutrients
(glucose,
amino
acids
lipids)
fuel
immune
activation.
also
inhibits
nutrient
consumption
peripheral
(non-immune)
organs,
effect
provide
prioritisation
fuels
for
responses.
However,
decrease
organs
result
decreased
mitochondrial
production
ATP
(energy)
subsequently
impaired
function.
New England Journal of Medicine,
Год журнала:
2021,
Номер
384(9), С. 808 - 817
Опубликована: Март 3, 2021
Infection
and
increased
systemic
inflammation
cause
organ
dysfunction
death
in
patients
with
decompensated
cirrhosis.
Preclinical
studies
provide
support
for
an
antiinflammatory
role
of
albumin,
but
confirmatory
large-scale
clinical
trials
are
lacking.
Whether
targeting
a
serum
albumin
level
30
g
per
liter
or
greater
these
repeated
daily
infusions
20%
human
solution,
as
compared
standard
care,
would
reduce
the
incidences
infection,
kidney
dysfunction,
is
unknown.
Journal of Hepatology,
Год журнала:
2020,
Номер
74(5), С. 1097 - 1108
Опубликована: Ноя. 20, 2020
Acute
decompensation
(AD)
of
cirrhosis
may
present
without
acute-on-chronic
liver
failure
(ACLF)
(AD-No
ACLF),
or
with
ACLF
(AD-ACLF),
defined
by
organ
failure(s).
Herein,
we
aimed
to
analyze
and
characterize
the
precipitants
leading
both
these
AD
phenotypes.
The
multicenter,
prospective,
observational
PREDICT
study
(NCT03056612)
included
1,273
non-electively
hospitalized
patients
(No
=
1,071;
202).
Medical
history,
clinical
data
laboratory
were
collected
at
enrolment
during
90-day
follow-up,
particular
attention
given
following
characteristics
precipitants:
induction
dysfunction
failure,
systemic
inflammation,
chronology,
intensity,
relationship
outcome.
Among
various
events,
4
distinct
events
consistently
related
AD:
proven
bacterial
infections,
severe
alcoholic
hepatitis,
gastrointestinal
bleeding
shock
toxic
encephalopathy.
in
AD-No
cohort
AD-ACLF
(38%
71%,
respectively),
almost
all
(96%
97%,
respectively)
showed
infection
either
alone
combination
other
events.
Survival
was
similar
infections
hepatitis
number
associated
significantly
increased
mortality
paralleled
increasing
levels
surrogates
for
inflammation.
Importantly,
adequate
first-line
antibiotic
treatment
a
lower
development
rate
mortality.
This
identified
that
are
course
prognosis
AD.
Specific
preventive
therapeutic
strategies
targeting
improve
outcomes
decompensated
cirrhosis.
is
characterized
rapid
deterioration
patient
health.
precipitating
cause
Proven
combination,
accounted
(96-97%)
cases
failure.
Whilst
type
precipitant
not
mortality,
precipitant(s)
was.
outcomes.
Journal of Hepatology,
Год журнала:
2021,
Номер
75, С. S67 - S81
Опубликована: Май 23, 2021
Cirrhosis
-
the
common
end-stage
of
chronic
liver
disease
is
associated
with
a
cascade
events,
which
intestinal
bacterial
overgrowth
and
dysbiosis
are
central.
Bacterial
toxins
entering
portal
or
systemic
circulation
can
directly
cause
hepatocyte
death,
while
also
affects
gut
barrier
function
increases
translocation,
leading
to
infections,
inflammation
vasodilation,
contribute
acute
decompensation
organ
failure.
Acute
its
severe
forms,
pre-acute-on-chronic
failure
(ACLF)
ACLF,
characterised
by
sudden
dysfunction
(and
failure)
high
short-term
mortality.
Patients
pre-ACLF
ACLF
present
high-grade
inflammation,
usually
precipitated
proven
infection
and/or
alcoholic
hepatitis.
However,
no
precipitant
identified
in
30%
these
patients,
whom
translocation
from
microbiota
assumed
be
responsible
for
decompensation.
Different
profiles
may
influence
rate
thereby
outcome
patients.
Thus,
targeting
promising
strategy
prevention
treatment
decompensation,
ACLF.
Approaches
include
use
antibiotics
such
as
rifaximin,
faecal
microbial
transplantation
enterosorbents
(e.g.
Yaq-001),
bind
factors
without
exerting
direct
effect
on
growth
kinetics.
This
review
focuses
role
strategies
prevent
Background
and
aims
Acute-on-chronic
liver
failure
(ACLF)
is
characterised
by
acute
decompensation
of
cirrhosis
associated
with
organ
failures.
We
systematically
evaluated
the
geographical
variations
ACLF
across
world
in
terms
prevalence,
mortality,
aetiology
chronic
disease
(CLD),
triggers
Methods
searched
EMBASE
PubMed
from
3/1/2013
to
7/3/2020
using
ACLF-EASL-CLIF
(European
Association
for
Study
Liver-Chronic
Liver
Failure)
criteria.
Two
investigators
independently
conducted
abstract
selection/abstraction
CLD,
triggers,
failures
prevalence/mortality
presence/grade
ACLF.
grouped
countries
into
Europe,
East/South
Asia
North/South
America.
calculated
pooled
proportions,
methodological
quality
Newcastle-Ottawa
Scale
statistical
heterogeneity,
performed
sensitivity
analyses.
Results
identified
2369
studies;
30
cohort
studies
met
our
inclusion
criteria
(43
206
patients
140
835
without
ACLF).
The
global
prevalence
among
admitted
decompensated
was
35%
(95%
CI
33%
38%),
highest
South
at
65%.
90-day
mortality
58%
51%
64%),
America
73%.
Alcohol
most
frequently
reported
underlying
CLD
(45%,
95%
41
50).
Infection
frequent
trigger
(35%)
kidney
dysfunction
common
(49%).
Sensitivity
analyses
showed
regional
estimates
grossly
unchanged
high-quality
studies.
Type
design,
country
health
index,
explained
variation
estimates.
Conclusions
are
high.
Region-specific
could
be
type
triggers/aetiology
or
grade.
Health
systems
will
need
tailor
early
recognition
treatment
based
on
region-specific
data.
