The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases
Hepatology,
Год журнала:
2017,
Номер
67(1), С. 328 - 357
Опубликована: Июль 17, 2017
Potential
conflict
of
interest:
Dr.
Chalasani
consults
for
and
received
grants
from
Eli
Lilly.
He
NuSirt,
AbbVie,
Afimmune,
Tobira,
Madrigal,
Shire,
Cempra,
Ardelyx,
Axovant,
Amarin.
Intercept,
Gilead,
Galectin,
Cumberland.
Younossi
Bristol‐Myers
Squibb,
Allergan,
GlaxoSmithKline.
advises
Vertex
Janssen.
Brunt
Gilead.
Charlton
NGM
Bio,
Genfit,
Novartis.
Conatus.
Cusi
Novo
Nordisk.
Tobira.
Cirius,
Novartis,
Janssen,
Zydus,
Nordic,
Rinella
Nusirt.
She
Fibrogen,
Immuron,
Enanta,
AbbVie.
Harrison
Echosens,
Prometheus,
Perspectum,
HistoIndex.
Garland,
Pfizer.
is
on
the
speakers'
bureau
Alexion.
Sanyal
Salix,
Conatus,
malinckrodt,
Echosens‐Sandhill,
Sequana.
employed
by
Bio.
owns
stock
in
GenFit,
Hemoshear,
Durect,
Indalo.
Pfizer,
Boehringer
Ingleheim,
Nimbus,
Nitto
Denko,
Lilly,
Nordisk,
Fractyl,
Chemomab,
Affimmune,
Teva,
Ardelyx.
Squibb
Merck.
royalties
UptoDate.
Exhalenz,
Arkana,
NewCo
LLC.
The
funding
development
this
Practice
Guidance
was
provided
American
Association
Study
Liver
Diseases.
This
practice
guidance
approved
Diseases
June
15,
2017.
Preamble
provides
a
data‐supported
approach
to
diagnostic,
therapeutic,
preventive
aspects
nonalcoholic
fatty
liver
disease
(NAFLD)
care.
A
"Guidance"
document
different
"Guideline."
Guidelines
are
developed
multidisciplinary
panel
experts
rate
quality
(level)
evidence
strength
each
recommendation
using
Grading
Recommendations,
Assessment
Development,
Evaluation
system.
topic,
statements,
not
recommendations,
put
forward
help
clinicians
understand
implement
most
recent
evidence.
commissioned
(AASLD)
an
update
Guideline
published
2012
conjunction
with
Gastroenterology
College
(ACG).1
Sections
where
there
have
been
no
notable
newer
publications
modified,
so
some
paragraphs
remain
unchanged.
narrative
review
statements
based
following:
(1)
formal
analysis
recently
world
literature
topic
(Medline
search
up
August
2016);
(2)
Physicians'
Manual
Assessing
Health
Practices
Designing
Guidelines2;
(3)
guideline
policies
AASLD;
(4)
experience
authors
independent
reviewers
regard
NAFLD.
intended
use
physicians
other
health
professionals.
As
clinically
appropriate,
should
be
tailored
individual
patients.
Specific
whenever
possible,
and,
when
such
available
or
inconsistent,
made
consensus
opinion
authors.3
rather
than
article,
interested
readers
can
refer
several
comprehensive
reviews.4
Because
lengthy,
make
it
easier
reader,
list
all
recommendations
tabular
form
as
Supporting
Table
S1.
Definitions
For
defining
NAFLD,
must
hepatic
steatosis
(HS),
either
imaging
histology,
lack
secondary
causes
fat
accumulation
significant
alcohol
consumption,
long‐term
steatogenic
medication,
monogenic
hereditary
disorders
(Table
1).
In
majority
patients,
NAFLD
commonly
associated
metabolic
comorbidities
obesity,
diabetes
mellitus,
dyslipidemia.
categorized
histologically
into
(NAFL)
steatohepatitis
(NASH;
2).
NAFL
defined
presence
≥5%
HS
without
hepatocellular
injury
hepatocyte
ballooning.
NASH
inflammation
(e.g.,
ballooning),
any
fibrosis.
"advanced"
fibrosis,
will
referring
specifically
stages
3
4,
that
is,
bridging
fibrosis
cirrhosis.
1
-
Common
Causes
Secondary
Macrovesicular
‐
Excessive
consumption
Hepatitis
C
(genotype
3)
WD
Lipodystrophy
Starvation
Parenteral
nutrition
Abetalipoproteinemia
Medications
mipomersen,
lomitapide,
amiodarone,
methotrexate,
tamoxifen,
corticosteroids)
Microvesicular
Reye's
syndrome
(valproate,
antiretroviral
medicines)
Acute
pregnancy
HELLP
Inborn
errors
metabolism
lecithin‐cholesterol
acyltransferase
deficiency,
cholesterol
ester
storage
disease,
Wolman's
disease)
2
Related
Encompasses
entire
spectrum
FLD
individuals
ranging
SH
cirrhosis
Presence
ballooning
hepatocytes
risk
progression
failure
considered
minimal.
(ballooning)
progress
cirrhosis,
failure,
rarely
cancer.
current
previous
histological
Cryptogenic
obvious
etiology.
Patients
cryptogenic
heavily
enriched
factors
obesity
MetS.
NAS
An
unweighted
composite
steatosis,
lobular
inflammation,
scores.
useful
tool
measure
changes
histology
patients
clinical
trials.
Fibrosis
scored
separately.126
SAF
score
semiquantitative
consisting
amount,
activity
(lobular
plus
fibrosis.130
Incidence
Prevalence
General
Population
INCIDENCE
OF
There
paucity
data
regarding
incidence
general
population.
few
studies
reported
Asian
countries,
which
briefly
summarized
below:
study
followed
11,448
subjects
5
years,
documented
ultrasound
12%
(n
=
1,418).10
635
Nagasaki
atomic
bomb
survivors
who
were
11.6
19.9
per
1,000
person‐years.11
565
subjects,
at
3‐5
diagnosed
magnetic
resonance
(MR)
(MRI)
transient
elastography
(TE),
estimated
13.5%
(34
person‐years).12
cohort
study,
77,425
free
baseline
average
4.5
years.
During
348,193.5
person‐years
follow‐up,
10,340
participants
ultrasound,
translating
29.7
person‐years.13
rates
population
Western
countries
even
less
reported:
England
International
Classification
Diseases,
Tenth
Revision
(ICD‐10)
codes
29
100,000
person‐years.
Given
inaccuracy
administrative
coding
ICD‐10,
likely
underestimates
true
NAFLD.14
Israel
28
person‐years.15
meta‐analysis
pooled
regional
Asia
52.34
(95%
confidence
interval
[CI],
28.31‐96.77)
whereas
West
around
CI,
19.34‐40.57).16
PREVALENCE
contrast
data,
significantly
higher
number
describing
prevalence
These
epidemiology
NAFLD:
overall
global
25.24%
22.10‐28.65).16
highest
Middle
East
(31.79%
[95%
13.48‐58.23])
South
America
(30.45%
22.74‐39.440])
lowest
Africa
(13.48%
[5.69‐28.69]).16
described
elsewhere,
gold
standard
diagnosing
remains
biopsy.
biopsy
feasible
population,
direct
assessment
NASH.
Nevertheless,
attempts
estimate
indirect
means.16
following
paragraphs:
among
had
"clinical
indication"
59.10%
47.55‐69.73).16
specific
(random
living‐related
donors,
etc.)
6.67%
2.17‐18.73)
29.85%
22.72‐38.12).16
these
estimates,
one
estimates
ranges
between
1.5%
6.45%.16
High‐Risk
Groups
Features
(MetS)
only
highly
prevalent
but
components
MetS
also
increase
developing
NAFLD.16
bidirectional
association
has
strongly
established.
context,
established
conditions
(obesity,
type
diabetes,
hypertension,
dyslipidemia)
emerging
(sleep
apnea,
colorectal
cancer,
osteoporosis,
psoriasis,
endocrinopathies,
polycystic
ovary
obesity)
NAFLD.21
Obesity
(excessive
body
mass
index
[BMI]
visceral
common
well‐documented
factor
fact,
overweight
obese
severely
obese,
(>95%)
severe
undergoing
bariatric
surgery
NAFLD.23
Type
mellitus
(T2DM):
very
high
T2DM.
suggested
third
two
thirds
diabetic
NAFLD.18
It
important
remember
importance
T2DM
develop
almost
simultaneously
patient,
confounds
its
causal
relationship
require
additional
investigation.28
Dyslipidemia:
High
serum
triglyceride
(TG)
levels
low
high‐density
lipoprotein
(HDL)
dyslipidemia
attending
lipid
clinics
50%.29
large,
cross‐sectional
conducted
44,767
Taiwanese
attended
single
clinic,
enrollees
stratified
four
subgroups
their
total
HDL‐cholesterol
TG
ratios.
53.76%;
however,
those
ratios
33.41%,
group
78.04%.
Age,
sex,
ethnicity:
may
vary
according
age,
ethnicity.31
both
stage
appear
age.34
Risk
Factors
Associated
With
Conditions
Established
Other
Hypothyroidism
Obstructive
sleep
apnea
Dyslipidemia
Hypopituitarism
MetSa
Hypogonadism
Polycystic
Pancreatoduodenal
resection
Psoriasis
aThe
Adult
Treatment
Panel
III
definition
requires
three
more
features:
waist
circumference
greater
102
cm
men
88
women;
level
150
mg/dL
greater;
HDL
40
50
systolic
blood
pressure
130
mm
Hg
diastolic
85
(5)
fasting
plasma
glucose
110
greater.287
Although
controversial,
male
sex
Furthermore,
times
women.33
issues
ethnicity
impact
evolved
over
initial
reports
compared
non‐Hispanic
whites,
Hispanic
blacks
lower
NAFLD.39
American‐Indian
Alaskan‐Native
populations
seem
(0.6%‐2.2%),
need
confirmed.31
intriguing
suggest
ethnic
differences
explained
genetic
variation
related
patatin‐like
phospholipase
domain‐containing
protein
(PNPLA‐3)
gene.40
summary,
varies
across
world,
28.01
19.34‐40.57)
28.31‐96.77).
Natural
History
Outcomes
Over
past
decades,
natural
history
NAFLD.1
growing
NASH,
especially
degree
adverse
outcomes
liver‐related
mortality.1
shown
increased
mortality
matched
control
NAFLD.53
cause
death
cardiovascular
(CVD),
comorbidities.
12th
leading
second
NAFLD.55
Cancer‐related
top
rate.56
meta‐analysis,
liver‐specific
determined
0.77
(range,
0.33‐1.77)
11.77
7.10‐19.53)
15.44
11.72‐20.34)
25.56
6.29‐103.80),
respectively.16
1.94
1.28‐2.92)
1.05
0.70‐1.56),
feature
fibrosis;
specifically,
zone
sinusoidal
periportal
(stage
2)
advanced
(bridging
[stage
3]
4]).
independently
predictive
mortality.44
now
third‐most
carcinoma
(HCC)
United
States,
attributed
enormous
condition.60
epidemic
NAFLD‐related
HCC
9%
annual
rate.61
older,
shorter
survival
time,
often
heart
die
primary
cancer
patients.60
Around
13%
Veteran
Administration
did
Among
factors,
having
absence
confirms
small
cirrhosis.62
recognize
what
"burned
out"
NAFLD.63
particular
disproportionately
(T2DM,
MetS)
resemble
pathological
seldom
features
consistent
cirrhosis.63
Important
One
surrogates
documentation
progressive
(HF).
HF
showed
mean
0.09
0.06‐0.12).16
Several
investigated
comparison
hepatitis
cirrhosis.9
prospective,
U.S.‐based
observed
decompensation
cirrhosis.65
However,
international
247
cirrhosis)
duration
85.6
±
54.5
months
10‐year
81.5%—a
cirrhosis.1
confirmed
increasing
numbers
presenting
requiring
transplantation
(LT).
ranked
second‐most
LT
overtake
future,
virus
(HCV)
treated
curative
antiviral
regimens.9
noted
previously,
another
important,
outcome
HCC.
0.44
0.29‐0.66)
person‐years.16
HCC,
54.9%
cases
HCV,
16.4%
alcoholic
14.1%
9.5%
B
virus.
given
extremely
large
within
population.61
Alcohol
Consumption
Definition
By
definition,
indicates
ongoing
amounts
alcohol.
precise
suspected
uncertain.
meeting
recommended
that,
trials
candidate
eligibility
purposes,
>21
drinks
week
>14
women
2‐year
period
preceding
histology.68
According
National
Institute
Abuse
Alcoholism
(NIAAA),
drink
contains
about
14
g
pure
alcohol.69
Unfortunately,
inconsistent.70
Statement:
1.
Ongoing
reasonable
threshold
evaluating
Incidentally
Discovered
HEPATIC
STEATOSIS
(HS)
Some
thoracic
abdominal
reasons
symptoms,
signs,
abnormal
biochemistry
demonstrate
unsuspected
HS.
11%
incidentally
discovered
calculated
(NFS).71
optimal
diagnostic
management
strategies
patient
investigated.
Statements:
2.
detected
symptoms
signs
attributable
chemistries
evaluated
though
they
worked
accordingly.
3.
incidental
normal
biochemistries
assessed
alternate
medications.
Screening
Primary
Care,
Diabetes,
Clinics
argued
systematic
screening
least
higher‐risk
obesity.
example,
do
suggests
patients.72
gaps
our
knowledge
diagnosis,
history,
treatment
recent,
cost‐effective
Markov
model
present,
because
disutility
treatment.75
sufficiently
sensitive
serve
tests,
TE
potentially
sensitive,
utility
tools
unproven.
called
"vigilance"
chronic
(CLD)
routine
screening.76
4.
Routine
high‐risk
groups
care,
advised
time
uncertainties
surrounding
tests
options,
along
benefits
cost‐effectiveness
screening.
5.
suspicion
diabetes.
Clinical
decision
aids
NFS
fibrosis‐4
(FIB‐4)
vibration
controlled
(VCTE)
used
identify
cirrhosis).
Family
Members
familial
clustering
NAFLD.77
retrospective
Willner
et
al.
18%
similarly
affected
first‐degree
relative.80
aggregation
children
after
adjusting
race,
BMI,
heritability
MR‐measured
fraction
0.386,
present
family
members
elevated
alanine
aminotransferase
(ALT)
obesity.81
Data
reporting
variable,
detectable
heritability,
Hungarian
twin
cohort,
nearly
universal
adolescents.77
ongoing,
well‐characterized
community‐dwelling
twins
California,
MRI
quantify
correlated
monozygotic,
dizygotic,
pairs,
multivariable
adjustment,
0.52
0.31‐0.73;
P
<
1.1
×
10–11)
0.50
0.28‐0.72;
6.1
10–1),
respectively.84
6.
Systematic
currently.
Initial
Patient
Suspected
diagnosis
competing
etiologies
HS,
coexisting
CLD.
alternative
C,
medications,
parenteral
nutrition,
Wilson's
(WD),
malnutrition
When
newly
exclude
CLD,
including
hemochromatosis,
autoimmune
viral
hepatitis,
alpha‐1
antitrypsin
WD,
drug‐induced
injury.
Serological
evaluation
uncover
laboratory
abnormalities
always
reflect
disease.
Two
examples
ferritin
antibodies.
Mildly
does
necessarily
indicate
iron
overload,
progression.
somewhat
conflicting,
>1.5
upper
limit
(ULN)
628
adults.85
If
transferrin
saturation
hemochromatosis
excluded.
Mutations
HFE
gene
occur
variable
frequency
significance
unclear.86
setting
determine
extent
Low
titers
autoantibodies,
particularly
antismooth
muscle
antinuclear
antibodies,
generally
epiphenomenon
consequence,
864
Research
Network
(NASH
CRN),
elevations
autoantibodies
(antinuclear
antibodies
>1:160
>1:40)
21%
atypical
features.87
While
diseases
being
excluded,
carefully
taken
comorbidities,
central
dyslipidemia,
insulin
resistance
(IR),
hypothyroidism,
syndrome,
obstructive
apnea.
7.
essential
8.
persistently
ferritin,
saturation,
context
homozygote
heterozygote
C282Y
mutation,
considered.
9.
suggestive
(>5
ULN
aminotransferases,
globulins,
albumin
ratio)
prompt
work‐up
10.
consider
IR
Noninvasive
Steatohepatitis
Advanced
fairly
dichotomous—NAFL
benign,
currently
reliable
identifying
(SH)
acknowledged
limited
cost,
sampling
error,
procedure‐related
morbidity
mortality.
Serum
computed
tomography
(CT),
MR,
reliably
Therefore,
interest
prediction
rules
noninvasive
biomarkers
detailed
discussion
beyond
scope
guidance.47
NONINVASIVE
QUANTIFICATION
IN
predict
severity
SH)88
NAFLD.89
MR
imaging,
spectroscopy92
proton
density
fraction,93
excellent
modality
quantifying
widely
trials.95
obtain
continuous
attenuation
parameters
promising
ambulatory
setting.74
noninvasively
qua
Язык: Английский
A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement
Journal of Hepatology,
Год журнала:
2020,
Номер
73(1), С. 202 - 209
Опубликована: Апрель 8, 2020
Язык: Английский
Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease
Hepatology,
Год журнала:
2017,
Номер
67(1), С. 123 - 133
Опубликована: Авг. 12, 2017
Nonalcoholic
fatty
liver
disease
(NAFLD)
and
resulting
nonalcoholic
steatohepatitis
(NASH)
are
highly
prevalent
in
the
United
States,
where
they
a
growing
cause
of
cirrhosis
hepatocellular
carcinoma
(HCC)
increasingly
an
indicator
for
transplantation.
A
Markov
model
was
used
to
forecast
NAFLD
progression.
Incidence
based
on
historical
projected
changes
adult
prevalence
obesity
type
2
diabetes
mellitus
(DM).
Assumptions
were
derived
from
published
literature
available
validated
using
national
surveillance
data
incidence
NAFLD‐related
HCC.
Projected
cirrhosis,
advanced
disease,
liver‐related
mortality
quantified
through
2030.
Prevalent
cases
forecasted
increase
21%,
83.1
million
(2015)
100.9
(2030),
while
NASH
will
63%
16.52
27.00
cases.
Overall
among
population
(aged
≥15
years)
is
at
33.5%
2030,
median
age
50
55
years
during
2015‐2030.
In
2015,
approximately
20%
classified
as
NASH,
increasing
27%
by
reflection
both
progression
aging
population.
decompensated
168%
105,430
HCC
137%
12,240
Liver
deaths
178%
estimated
78,300
During
2015‐2030,
there
be
nearly
800,000
excess
deaths.
Conclusion:
With
continued
high
rates
DM
along
with
population,
States.
Strategies
slow
growth
therapeutic
options
necessary
mitigate
burden.
(H
epatology
2018;67:123‐133).
Язык: Английский
The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis
Journal of Hepatology,
Год журнала:
2019,
Номер
71(4), С. 793 - 801
Опубликована: Июль 4, 2019
Язык: Английский
Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030
Journal of Hepatology,
Год журнала:
2018,
Номер
69(4), С. 896 - 904
Опубликована: Июнь 7, 2018
Non-alcoholic
fatty
liver
disease
(NAFLD)
and
non-alcoholic
steatohepatitis
(NASH)
are
increasingly
a
cause
of
cirrhosis
hepatocellular
carcinoma
globally.
This
burden
is
expected
to
increase
as
epidemics
obesity,
diabetes
metabolic
syndrome
continue
grow.
The
goal
this
analysis
was
use
Markov
model
forecast
NAFLD
using
currently
available
data.A
used
estimate
NASH
progression
in
eight
countries
based
on
data
for
adult
prevalence
obesity
type
2
mellitus
(DM).
Published
estimates
expert
consensus
were
build
validate
the
projections.If
DM
level
off
future,
we
project
modest
growth
total
cases
(0-30%),
between
2016-2030,
with
highest
China
result
urbanization
lowest
Japan
shrinking
population.
However,
at
same
time,
will
15-56%,
while
mortality
advanced
more
than
double
an
aging/increasing
population.NAFLD
represent
large
growing
public
health
problem
efforts
understand
epidemic
mitigate
needed.
If
current
historical
rates,
both
increase.
Since
reversible,
campaigns
awareness
diagnosis,
promote
diet
exercise
can
help
manage
future
burden.Non-alcoholic
lead
disease.
Both
conditions
becoming
prevalent
A
mathematical
built
how
associated
change
over
time.
Results
suggest
increasing
liver-related
coming
years.
Язык: Английский
Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis
Journal of Hepatology,
Год журнала:
2016,
Номер
65(3), С. 589 - 600
Опубликована: Май 18, 2016
Язык: Английский
NAFLD and diabetes mellitus
Nature Reviews Gastroenterology & Hepatology,
Год журнала:
2016,
Номер
14(1), С. 32 - 42
Опубликована: Окт. 12, 2016
Язык: Английский
Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies
The Lancet Diabetes & Endocrinology,
Год журнала:
2018,
Номер
7(4), С. 313 - 324
Опубликована: Авг. 30, 2018
Язык: Английский
Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta‐analysis
Journal of Gastroenterology and Hepatology,
Год журнала:
2015,
Номер
31(5), С. 936 - 944
Опубликована: Дек. 15, 2015
Abstract
Background
and
Aim:
The
magnitude
of
the
risk
incident
type
2
diabetes
(T2D)
metabolic
syndrome
(MetS)
among
patients
with
nonalcoholic
fatty
liver
disease
(NAFLD)
is
poorly
known.
We
gauged
developing
T2D
MetS
in
NAFLD
diagnosed
by
either
serum
enzymes
(aminotransferases
or
gamma‐glutamyltransferase
[GGT])
ultrasonography.
Methods:
Pertinent
prospective
studies
were
identified
through
extensive
electronic
database
research,
fulfilling
enrolment
criteria
included
meta‐analysis.
Results
Overall,
a
pooled
population
117020
(from
20
studies),
who
followed‐up
for
median
period
5
years
(range:
3–14.7
years),
was
associated
an
increased
relative
1.97
(95%
confidence
interval
[CI],
1.80–2.15)
alanine
aminotransferase,
1.58
CI,
1.43–1.74)
aspartate
1.86
1.71–2.03)
GGT
(last
vs
first
quartile
quintile),
1.76–1.95)
ultrasonography,
respectively.
81411
eight
studies)
4.5
3–11
1.80
1.72–1.89)
aminotransferase
1.98
1.89–2.07)
GGT,
3.22
3.05–3.41)
Conclusions:
Nonalcoholic
disease,
as
significantly
increases
over
5‐year
follow‐up.
Язык: Английский
Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence?
Journal of Hepatology,
Год журнала:
2017,
Номер
68(2), С. 335 - 352
Опубликована: Ноя. 6, 2017
Язык: Английский