Strong correlation by ultrasonography of hepatomegaly and the presence of co-infection in HIV/HCV cirrhotic patients

Abstract

Objectives:
Progression of hepatic fibrosis is accelerated in patients co-infected with human immunodeficiency virus and hepatitis C virus compared to hepatitis C virus mono-infected patients. This study aimed to compare ultrasound features and selected clinical and biochemical variables between patients with human immunodeficiency virus/hepatitis C virus co-infection (n=16) versus hepatitis C virus mono-infection (n=16).

Methods:
Each patient underwent abdominal ultrasound, and a specific evaluation was performed in order to detect findings consistent with chronic liver disease. Characterization of spleen size, liver structural pattern, diameter of the portal, spleen, and mesenteric veins was based on classical ultrasound parameters. Propensity score was used for control of selection bias and performed using binary logistic regression to generate a score for each patient. The Fisher and Mann-Whitney tests were used to evaluate categorical variables and continuous variables, respectively.

Results:
On univariate analysis right hepatic lobe size was larger in human immunodeficiency virus/hepatitis C virus patients (157.06 ± 17.56 mm) compared to hepatitis C virus mono-infected patients (134.94 ± 16.95 mm) (p=0.0011). The left hepatic lobe was also significantly larger in human immunodeficiency virus/hepatitis C virus patients (115.88 ± 22.69 mm) versus hepatitis C virus mono-infected patients (95.06 ± 24.18 mm) (p=0.0177). Also, there was a strong correlation between hepatomegaly and co-infection (p=0.005).

Conclusion:
Human immunodeficiency virus infection was the primary variable influencing liver enlargement in this population. Hepatomegaly on ultrasound was more common among cirrhotic human immunodeficiency virus/hepatitis C virus co-infected patients than among cirrhotic hepatitis C virus mono-infected patients. This aspect is very important in the management of human immunodeficiency virus/hepatitis C virus co-infected patients, because screening for hepatocellular carcinoma is necessary in this population.

Full text

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The
Brazilian
Journal
of
INFECTIOUS
DISEASES
www.elsevier.com/locate/bjid
Original
article
Strong
correlation
by
ultrasonography
of
hepatomegaly
and
the
presence
of
co-infection
in
HIV/HCV
cirrhotic
patients
Denise
Cerqueira
Paranaguá
Vezozzoa,∗,
Maria
Cassia
Mendes-Correab,
Marlone
Cunha-Silvaa,
Mónica
Viviana
Alvarado-Mora a,
João
Ítalo
Dias
Franc¸aa,
José
Luiz
Sebbaa,
Antonio
Carlos
Nicodemob,
Claudia
P.M.S.
Oliveiraa,
Flair
José
Carrilhoa
aDepartment
of
Gastroenterology,
Medical
School,
Universidade
de
São
Paulo,
São
Paulo,
SP,
Brazil
bDepartment
of
Infectious
Diseases,
Medical
School,
Universidade
de
São
Paulo,
São
Paulo,
SP,
Brazil
a
r
t
i
c
l
e
i
n
f
o
Article
history:
Received
11
May
2012
Accepted
26
September
2012
Available
online
27
February
2013
Keywords:
Ultrasonography
HIV/HCV
co-infection
Hepatomegaly
Liver
size
Cirrhosis
a
b
s
t
r
a
c
t
Objectives:
Progression
of
hepatic
fibrosis
is
accelerated
in
patients
co-infected
with
human
immunodeficiency
virus
and
hepatitis
C
virus
compared
to
hepatitis
C
virus
mono-infected
patients.
This
study
aimed
to
compare
ultrasound
features
and
selected
clinical
and
bio-
chemical
variables
between
patients
with
human
immunodeficiency
virus/hepatitis
C
virus
co-infection
(n
=
16)
versus
hepatitis
C
virus
mono-infection
(n
=
16).
Methods:
Each
patient
underwent
abdominal
ultrasound,
and
a
specific
evaluation
was
per-
formed
in
order
to
detect
findings
consistent
with
chronic
liver
disease.
Characterization
of
spleen
size,
liver
structural
pattern,
diameter
of
the
portal,
spleen,
and
mesenteric
veins
was
based
on
classical
ultrasound
parameters.
Propensity
score
was
used
for
control
of
selection
bias
and
performed
using
binary
logistic
regression
to
generate
a
score
for
each
patient.
The
Fisher
and
Mann–Whitney
tests
were
used
to
evaluate
categorical
variables
and
continuous
variables,
respectively.
Results:
On
univariate
analysis
right
hepatic
lobe
size
was
larger
in
human
immuno-
deficiency
virus/hepatitis
C
virus
patients
(157.06
±
17.56
mm)
compared
to
hepatitis
C
virus
mono-infected
patients
(134.94
±
16.95
mm)
(p
=
0.0011).
The
left
hepatic
lobe
was
also
significantly
larger
in
human
immunodeficiency
virus/hepatitis
C
virus
patients
(115.88
±
22.69
mm)
versus
hepatitis
C
virus
mono-infected
patients
(95.06
±
24.18
mm)
(p
=
0.0177).
Also,
there
was
a
strong
correlation
between
hepatomegaly
and
co-infection
(p
=
0.005).
Conclusion:
Human
immunodeficiency
virus
infection
was
the
primary
variable
influenc-
ing
liver
enlargement
in
this
population.
Hepatomegaly
on
ultrasound
was
more
common
among
cirrhotic
human
immunodeficiency
virus/hepatitis
C
virus
co-infected
patients
than
among
cirrhotic
hepatitis
C
virus
mono-infected
patients.
This
aspect
is
very
important
in
the
management
of
human
immunodeficiency
virus/hepatitis
C
virus
co-infected
patients,
because
screening
for
hepatocellular
carcinoma
is
necessary
in
this
population.
©
2013
Elsevier
Editora
Ltda.
All
rights
reserved.
∗Corresponding
author
at:
Hepatology
Branch,
Department
of
Gastroenterology,
Medical
School,
Universidade
de
São
Paulo,
Av.
Dr.
Enéas
de
Carvalho
Aguiar,
255
São
Paulo,
SP
05403-000,
Brazil.
E-mail
address:
denise.paranagua@gmail.com
(D.C.P.
Vezozzo).
1413-8670/$
–
see
front
matter
©
2013
Elsevier
Editora
Ltda.
All
rights
reserved.
http://dx.doi.org/10.1016/j.bjid.2012.09.009

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Introduction
Chronic
hepatitis
is
one
of
the
most
relevant
co-morbidities
of
patients
co-infected
with
human
immunodeficiency
virus
(HIV)
and
hepatitis
C
virus
(HCV).1HIV-infected
patients
are
at
increased
risk
for
HCV
infection,
with
an
estimated
HCV
prevalence
of
30–35%
in
this
population.1Among
HIV-positive
drug
users,
the
reported
prevalence
of
HCV
is
up
to
80%.2,3
Patients
co-infected
with
HIV
and
HCV
develop
liver
disease
more
rapidly,
and
earlier
progression
to
liver
cirrhosis
has
been
described
in
this
population.4–7
Liver
cirrhosis
is
usually
suspected
on
the
basis
of
abnor-
malities
in
standard
liver
function,
biochemical
(blood)
tests,
non-invasive
methods
of
evaluating
fibrosis,
and
ultrasound
(US)
examination.
The
role
of
radiology
in
the
evaluation
of
liver
cirrhosis
is
primarily
to
characterize
the
morphologic
manifestations
of
the
disease,
evaluate
hepatic
and
extra-
hepatic
vasculature,
assess
the
effects
of
portal
hypertension,
and
detect
liver
tumors.
There
are
scarce
data
in
the
literature
regarding
US
stud-
ies
in
HIV/HCV
co-infected
patients,
particularly
those
with
liver
cirrhosis.
US
findings
could
influence
the
management
of
these
patients
in
terms
of
identifying
indications
for
liver
biopsy,
treatment,
and
surveillance
for
hepatocellular
carci-
noma.
The
aim
of
this
case–control
study
was
to
compare
US
fea-
tures
and
selected
clinical
and
biochemical
variables
among
HIV/HCV
co-infected
versus
HCV
mono-infected
patients
with
hepatic
cirrhosis
matched
for
age,
gender,
and
body
mass
index
(BMI).
We
aimed
to
answer
two
questions:
(1)
Is
there
any
difference
in
liver
size
between
co-infected
and
mono-infected
cirrhotic
patients?
(2)
Are
there
demographic
and
clinical
vari-
ables
related
to
liver
size?
Methods
Study
population
The
initial
study
population
was
45
patients,
including
28
HIV/HCV
co-infected
and
17
HCV
mono-infected
patients.
We
applied
a
propensity
score
using
three
demographic
char-
acteristics
(age,
gender,
and
BMI)
and
identified
16
patients
with
HIV/HCV
co-infection
(study
group)
and
16
patients
with
HCV
mono-infection
(control
group).
The
co-infected
patients
were
selected
among
patients
seeking
regular
care
at
the
AIDS
Outpatient
Clinic
of
the
Hospital
das
Clínicas,
Medi-
cal
School,
Universidade
de
São
Paulo.
HCV
mono-infected
patients
were
selected
from
those
registered
at
the
Depart-
ment
of
Gastroenterology,
Universidade
de
São
Paulo
School
of
Medicine.
Patients
were
selected
from
January
2006
to
January
2007.
All
patients
had
a
diagnosis
of
HCV
infection
(seropositive
for
HCV-RNA)
and
a
histopathological
diagnosis
of
liver
cir-
rhosis.
Each
patient
underwent
abdominal
US,
and
a
specific
evaluation
was
performed
in
order
to
detect
findings
consis-
tent
with
chronic
liver
disease
(liver
and
spleen
size,
liver
texture,
diameter
of
the
portal,
splenic,
and
superior
mesen-
teric
veins).
We
analyzed
the
following
additional
variables:
history
of
high
ethanol
consumption
(daily
intake
of
more
than
60
g
for
females
or
more
than
80
g
for
males
for
more
than
10
years),
HCV
genotype,
US
parameters,
and
the
presence
of
steatosis
on
liver
biopsy.
Patients
were
excluded
if
they
had
a
history
of
chronic
liver
disease
from
other
etiology
(including
hepatitis
B
virus
co-
infection),
opportunistic
infections,
or
other
serious
medical
conditions.
Liver
biopsy
Liver
biopsy
was
indicated
in
all
subjects
to
evaluate
the
sever-
ity
of
hepatic
disease.
The
decision
to
proceed
with
a
liver
biopsy
was
made
during
routine
work-up
for
chronic
hepati-
tis
C,
and
was
in
accordance
with
accepted
clinical
practice
by
physicians
staffing
the
Department
of
Gastroenterology
and
Infectious
Diseases
at
the
University
of
São
Paulo
School
of
Medicine.
Steatosis
on
liver
biopsies
was
graded
according
to
the
following
categories:
0
(minimal,
<5%),
1
(mild,
5–33%),
2
(moderate,
34–66%),
or
3
(severe,
>66%).
Biopsy
was
performed
at
a
mean
of
12
(standard
deviation
[SD]
3.6)
months
after
US
examination.
Ultrasound
examination
All
patients
underwent
US
of
the
abdomen.
The
opera-
tor
was
an
experienced
US
examiner
and
was
blinded
to
other
patient
variables.
Patients
were
in
the
supine
posi-
tion
for
all
examinations.
For
better
access
to
the
liver,
patients
were
instructed
to
raise
their
hands
behind
the
head,
thus
increasing
the
intercostal
spaces
and
the
distance
from
the
lower
costal
margin
to
the
iliac
crest.
US
exami-
nation
was
performed
during
deep
inspiration
and
with
a
relaxed
abdominal
wall.
In
each
case,
the
liver
was
examined
and
visualized
in
three
planes:
longitudinal,
cross-sectional,
and
diagonal.
Patients
fasted
for
an
average
of
6
h
prior
to
US.
A
specific
protocol
was
performed
to
evaluate
the
charac-
teristics
consistent
with
chronic
liver
disease
(liver
and
spleen
size,
liver
texture,
diameter
of
the
portal,
splenic,
and
mesen-
teric
veins).
The
right
hepatic
lobe
size
was
measured
in
accordance
to
prior
research:
the
cranio-caudal
diameter
was
determined
in
the
conventional
section
in
the
mid-clavicular
line,
by
measuring
from
the
hepatic
dome
to
the
inferior
hepatic
tip.8–10 The
left
hepatic
lobe
was
measured
at
the
median
line
of
the
abdomen,
parallel
to
the
aorta.
Normal
liver
size
was
defined
as
follows:
in
men
with
BMI
between
22
and
26
kg/m2and
women
with
BMI
between
22
and
25
kg/m2,
normal
liver
size
was
13.5
±
1.7
cm;
in
men
with
BMI
>
26
kg/m2and
women
with
BMI
>
25
kg/m2,
normal
liver
size
was
14.5
±
1.7
cm.10 Characterization
of
other
fea-
tures
(spleen
size,
liver
structural
pattern,
diameter
of
the
portal,
spleen,
and
mesenteric
veins)
was
based
on
classical
US
parameters.11
Portal
hypertension
was
defined
by
the
following
criteria:
(1)
portal
vein
diameter
larger
than
12
mm;
(2)
mesenteric
and
splenic
veins
larger
than
9
mm;
(3)
the
presence
of
collateral
routes;
and
(4)
spleen
index
larger
than
20
cm2[9].
Liver
steato-
sis
was
defined
on
US
by
the
observation
of
a
bright
liver
echo
pattern
or
by
the
loss
of
portal
venous
walls.12

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Clinical
and
viral
variables
Medical
records
were
retrospectively
reviewed
to
ascertain
demographic
and
clinical
characteristics,
and
to
obtain
lab-
oratory
data
preceding
the
US
examination.
An
electronic
and
written
database
containing
information
on
all
patients
was
used
as
the
source
of
laboratory
information.
On
the
day
of
the
US
examination,
measurements
of
body
weight
and
height
were
performed
in
a
standardized
fashion
by
clinical
research
coordinators.
The
local
Ethics
Committee
reviewed
and
approved
this
study.
All
patients
who
participated
in
the
study
provided
informed
consent.
Statistical
analysis
Propensity
score
was
used
for
control
of
selection
bias
and
per-
formed
using
binary
logistic
regression
to
generate
a
score
for
each
patient
(study
cases
and
controls).
Variables
included
in
the
propensity
model
were
age,
gender,
and
BMI.
The
Fisher
Exact
Test
was
used
to
verify
associations
between
categorical
variables.
The
Mann–Whitney
test
was
used
to
evaluate
con-
tinuous
variables.
p-Values
<0.05
were
considered
statistically
significant.
Results
Most
patients
were
male
(14
in
each
group
[87.5%]).
Mean
age
was
45.19
±
6.48
years
in
the
co-infected
group
and
48.13
±
4.44
years
in
the
mono-infected
group
(p
=
0.1453).
On
univariate
analysis,
right
hepatic
lobe
size
was
larger
in
HIV/HCV
co-infected
cirrhotic
patients
(157.06
±
17.56
mm)
compared
to
HCV
mono-infected
cirrhotic
patients
(134.94
±
16.95
mm)
(p
=
0.0011).
The
left
hepatic
lobe
was
also
significantly
larger
in
HIV/HVC
co-infected
patients
(115.88
±
22.69
mm)
versus
HCV
mono-infected
patients
(95.06
±
24.18
mm)
(p
=
0.0177).
Hepatomegaly
on
US
was
more
common
among
HIV/HCV
co-infected
patients
compared
to
HCV
mono-infected
patients.
Figs.
1
and
2
show
box
plots
of
the
right
and
left
hepatic
lobes
size,
respectively,
in
the
mono-
and
co-infected
groups.
To
categorize
hepatomegaly
we
adopted
a
cut-off
for
the
right
lobe
of
152
mm,
as
described
by
Kratzer
et
al.10 We
then
used
the
Fisher
Exact
Test
and
found
a
significant
correlation
between
hepatomegaly
and
co-infection
(p
=
0.005).
We
found
no
association
between
hepatomegaly
and
HCV
genotype
3
versus
non-3
(p
>
0.999).
On
univariate
analysis,
there
was
no
significant
differ-
ence
in
the
diameter
of
portal
(p
=
0.783),
superior
mesenteric
(p
=
0.5079),
or
splenic
veins
(p
=
0.5578)
between
groups.
Spleen
size
was
also
similar
in
both
groups
(p
=
0.6978).
Table
1
summarizes
US
liver
steatosis
grades
of
HIV/HCV
co-infected
patients
versus
HCV
mono-infected
patients.
There
was
no
difference
between
groups
in
terms
of
US
find-
ings
of
steatosis.
All
patients
had
a
histopathological
diagnosis
of
cirrho-
sis.
There
was
no
significant
difference
between
groups
in
the
degree
of
steatosis
by
histology
(p
>
0.05).
200
180
160
RHL (mm)
140
120
100
HCV
n=16
HIV/HCV
n=16
Group
Fig.
1
–
Box
plot
of
right
hepatic
lobe
(RHL)
measurement
in
HCV
(n
=
16)
and
HIV/HCV
(n
=
16)
infected
patients.
Bars
represent
minimum
and
maximum
sizes
recorded.
Horizontal
line
represents
the
median
value.
On
univariate
analysis,
there
was
no
significant
difference
between
groups
according
to
ethanol
consumption.
Discussion
Liver
enlargement
has
been
previously
observed
on
abdominal
US
in
HIV-infected
patients.13–15 We
performed
the
cur-
rent
investigation
to
determine
if
HIV
and
HCV
co-infection
produces
different
pathologic
findings.
We
found
that
some
patients
with
HIV/HCV
co-infection
had
larger
livers
than
mono-infected
patients,
even
in
the
presence
of
established
liver
cirrhosis.
This
is
a
notable
finding,
as
most
patients
with
cirrhosis
have
smaller
livers
than
non-cirrhotic
patients
with
liver
disease.
This
may
be
an
important
feature
in
evaluating
150
125
100
LHL (mm)
75
50
HCV
n=16
HIV/HCV
n=16
Group
Fig.
2
–
Box
plot
of
left
hepatic
lobe
(LHL)
measurement
in
HCV
(n
=
16)
and
HIV/HCV
(n
=
16)
infected
patients.
Bars
represent
minimum
and
maximum
sizes
recorded.
Horizontal
line
represents
the
median
value.

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Table
1
–
Demographic,
ultrasonographic,
and
histologic
characteristics
of
the
study
population.
HIV/HCV
HCV
p-value
Age
(years)
45.19
±
6.48
48.13
±
4.44
0.145
Male
gender
(%)
87.5
87.5
>0.999
BMI
(kg/m2)
23.85
±
3.40
25.73
±
3.91
0.156
High
ethanol
consumption
(%)
45.45
31.25
0.686
HCV
genotype
3
(%)
58.33
18.75
0.049
HCV
genotype
1
(%)
41.66
68.75
HCV
genotype
2
(%)
0
12.5
Right
hepatic
lobe
(mm)
157.06
±
17.56
134.94
±
16.95
0.001
Left
hepatic
lobe
(mm)
115.88
±
22.69
95.06
±
24.18
0.017
Steatosis
grade
on
ultrasound
Mild
(%) 6.25 12.5 >0.999
Moderate
(%)
6.25
6.25
High
(%)
18.75
12.5
Steatosis
grade
on
liver
histology
0
(%)
50.0
37.5
0.697
1
(%)
31.25
37.5
2
(%)
6.25
18.75
3
(%)
12.5
6.25
BMI,
body
mass
index.
these
patients
for
treatment
and
surveillance.
The
main
goal
of
this
study
was
to
determine
if
HIV/HCV
co-infected
patients
had
enlarged
livers
compared
to
HCV
mono-infected
patients.
To
evaluate
this
hypothesis
we
designed
a
case–control
study
including
16
patients
with
HIV/HCV
co-infection
and
16
patients
with
HCV
mono-infection,
with
groups
paired
using
propensity
score.
The
two
groups
were
similar
according
to
age,
gender,
and
BMI.
We
analyzed
some
demographic,
clin-
ical,
and
US
variables,
including
right
and
left
hepatic
lobe
size,
spleen
size,
and
portal,
superior
mesenteric,
and
splenic
vein
measurement
on
US
examination,
ethanol
consump-
tion,
HCV
genotype,
and
grade
of
steatosis
on
liver
biopsy.
Patients
were
excluded
if
they
had
a
history
of
chronic
liver
disease
from
another
etiology
(including
hepatitis
B
virus
co-
infection),
opportunistic
infections,
or
other
serious
medical
conditions.
We
found
that
co-infected
patients
had
significantly
larger
livers
than
mono-infected
patients
on
univariate
analysis.
To
determine
the
influence
of
other
factors
on
liver
size,
we
analyzed
demographic
and
clinical
variables;
on
univariate
analysis
there
was
no
significant
association
between
liver
size
and
ethanol
consumption,
liver
steatosis,
and
HCV
geno-
type.
Many
other
factors
may
influence
liver
size
in
these
patients;
it
was
not
the
objective
of
this
study
to
identify
all
significant
features
related
to
liver
size,
but
we
did
confirm
that
the
presence
of
HIV
infection
was
the
main
difference
between
the
two
groups.
Fat
infiltration
of
the
liver
can
cause
hepatomegaly.16 In
our
patient
population,
steatosis
might
play
a
role
in
liver
enlargement.
HCV
itself
can
result
in
fat
deposition
in
the
liver17 and
in
patients
with
chronic
hepatitis
C,
steatosis
is
associated
with
genotype
3,
probably
by
promoting
the
production
of
lipid-rich
VLDL
that
facilitates
maturation
of
HCV
precursors
by
optimizing
HCV
replication
and
thus
contributing
to
steatosis.18–21 We
did
not
find
a
significant
association
between
hepatomegaly
and
HCV
genotype
3.
Liver
steatosis
was
not
more
common
in
patients
with
larger
hepatic
size,
thus
we
could
not
identify
an
association
between
HCV
genotype
3
and
hepatomegaly
in
the
co-infected
group.
The
presence
of
HIV
infection
was
the
main
factor
we
found
differentiating
smaller
versus
larger
cirrhotic
livers.
The
etiology
of
steatosis
in
patients
with
HIV-HCV
co-
infection
is
indeed
multifactorial.
Therefore,
we
speculate
that
HIV-infected
patients
with
chronic
hepatitis
C
caused
by
HCV-3
who
are
taking
antiretroviral
therapy
may
be
par-
ticularly
prone
to
developing
liver
steatosis
and
more
severe
liver
fibrosis.
The
rising
rates
of
diabetes
and
obesity
among
HIV-infected
patients22,23 similar
to
the
general
US
popula-
tion,
may
also
contribute
to
non-alcoholic
fatty
liver
disease
(NAFLD)
in
this
patient
group.
In
addition,
studies
suggest
that
gut-derived
lipopolysaccharides
may
promote
hepatic
damage.24
Ethanol
ingestion
and
the
use
of
antiretroviral
drugs
(particularly
nucleoside
analogs)
are
often
reported
to
cause
liver
steatosis.25 HIV
is
associated
with
changes
in
lipid
metabolism,
as
well
as
with
the
development
of
metabolic
syndrome
with
lipoatrophy
or
lipodystrophy,
dys-
lipidemia,
peripheral
insulin
resistance,
and
increased
hepatic
steatosis.26
When
we
evaluated
right
hepatic
lobe
size,
measured
at
the
mid-clavicular
line,
we
found
co-infected
patients
to
have
larger
sizes
compared
to
mono-infected
patients
(p
=
0.0011).
A
recent
study
of
age-related
changes
in
abdominal
organ
struc-
ture
and
function
with
computed
tomography
and
positron
emission
tomography
showed
that
the
liver
enlarges
in
child-
hood,
but
we
clearly
see
a
continued
size
increase
up
to
49
years
of
age,
when
the
organ
volume
achieves
1606
mL
(18–49
years)
and
then
diminishes
to
1467
mL
(50–81
years).27 We
did
not
evaluate
the
effect
of
age
on
hepatic
size
because
we
used
age-matched
controls
for
comparison.
In
general,
diagnostic
imaging
techniques
are
claimed
to
be
superior
to
clinical
examination
in
determining
liver

154
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r
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j
i
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e
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t
d
i
s
.
2
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3;1
7(2):150–155
size.28,29 Nevertheless,
there
is
a
paucity
of
data
regarding
normal
and
borderline
values,
and
no
uniform
procedure
for
measuring
the
size
of
the
liver
has
been
established
that
can
serve
as
a
guideline
for
US
examination.30 In
a
study
published
by
Gosink
and
Leymaster,30 data
regarding
liver
specimens
obtained
at
autopsy
correlated
with
anthropomet-
ric
data
of
the
same
patient,
and
this
correlation
was
used
to
diagnose
hepatomegaly.
It
must
be
highlighted
that
the
estimation
of
liver
size
on
the
basis
of
a
single
parameter,
such
as
liver
diame-
ter
in
the
right
mid
clavicular
line,
is
limited,
considering
the
range
of
liver
morphotypes.31 Obesity,
accumulation
of
abdominal
gas,
and
uncooperative
patients
(lack
of
coordina-
tive
respiration)
are
other
known
limitations
of
this
method.
Despite
these
facts,
the
evaluation
of
hepatic
size
is
a
fre-
quent
issue
in
abdominal
US
(especially
for
the
determination
of
hepatomegaly),
and
this
method
complements
physical
examination.29 When
we
evaluated
the
left
lobe,
we
per-
formed
the
same
analysis
as
with
the
right
lobe,
with
similar
results.
The
common
finding
of
left
lobe
enlargement
in
liver
disease
helps
to
overcome
the
limitations
of
clinical
exami-
nation,
although
left
lobe
measurement
is
often
inaccurately
performed
and
is
not
standardized
for
routine
US.
To
the
best
of
our
knowledge,
the
present
study
is
the
first
to
report
enlargement
of
cirrhotic
livers
in
HIV/HCV
co-infected
patients.
In
general,
the
most
common
US
features
in
patients
with
cirrhosis
are
the
presence
of
irregularity
(irregular
sur-
face
and
liver
nodules)32 and
liver
atrophy.
In
more
advanced
stages
of
liver
disease,
the
liver
becomes
small
with
a
multin-
odular
surface,
decreased
portal
blood
flow
can
be
observed
by
Doppler,
and
eventually
ascites
can
be
detected.
Unlike
patients
with
cirrhosis
of
viral
origin,
patients
with
cirrhosis
of
alcoholic
origin
and
non-alcoholic
fatty
liver
disease
may
have
hepatomegaly
on
clinical
or
imaging
evaluation.33,34
The
finding
that
hepatomegaly
was
a
common
US
fea-
ture
among
cirrhotic
HIV/HCV
co-infected
patients
may
have
important
implications.
In
clinical
practice,
US
is
currently
used
to
predict
the
presence
of
cirrhosis
in
two
general
ways.
The
first
is
by
determining
the
presence
or
absence
of
portal
hypertension,
and
the
second
is
by
examining
the
size,
lobar
ratios,
echogenicity,
and
echotexture
of
the
liver.32 Although
the
signs
of
portal
hypertension
are
usually
recognized,
in
the
absence
of
other
clinical
or
image
abnormalities
suggestive
of
cirrhosis,
isolated
liver
enlargement
may
be
misdiagnosed
by
clinicians
as
evidence
of
other
clinical
conditions
related
to
HIV
infection
and
unrelated
to
cirrhotic
liver
disease.
Under
these
circumstances,
diagnostic
and
therapeutic
procedures
related
to
the
specific
liver
condition
may
be
postponed,
with
inevitable
consequences
to
the
patient.
This
study
had
some
limitations.
First,
liver
biopsies
were
not
performed
at
the
same
time
as
the
US
examinations.
Second,
laboratory
data
concerning
serum
triglycerides,
total
cholesterol,
high
density
lipoprotein,
and
fasting
glucose
lev-
els
were
not
always
collected
during
the
30
days
preceding
the
US
examination
or
liver
biopsy.
Therefore,
we
could
not
evaluate
the
association
between
serum
metabolic
and
non-
invasive
fibrosis
evaluation
tests
and
liver
enlargement.
These
limitations
may
have
contributed
to
the
fact
that
no
associa-
tion
was
observed
between
liver
enlargement
and
presence
of
liver
steatosis
on
biopsy.
Conclusions
In
conclusion,
the
presence
of
HIV
infection
was
the
primary
variable
influencing
liver
enlargement
in
this
population.
Hepatomegaly
was
a
more
common
US
feature
among
cir-
rhotic
HIV/HCV
co-infected
patients
than
among
cirrhotic
HCV
mono-infected
patients.
This
aspect
could
be
important
in
the
management
of
HIV/HCV
co-infected
patients,
because
screening
for
hepatocellular
carcinoma
is
necessary
in
this
population.
Conflict
of
interest
All
authors
declare
to
have
no
conflict
of
interest.
Acknowledgements
We
are
deeply
indebted
to
the
Alves
de
Queiroz
Family
Fund
for
the
continuous
sponsoring
support.
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