To evaluate of the effect of adding licorice to the standard treatment regimen of Helicobacter pylori

Abstract

Objective:
The aim of this study was to evaluate the effect of licorice in H. pylori eradication in patients suffering from dyspepsia either with peptic ulcer disease (PUD) or non-ulcer dyspepsia (NUD) in comparison to the clarithromycin-based standard triple regimen.

Methods:
In this randomized controlled clinical trial, 120 patients who had positive rapid urease test were included and assigned to two treatment groups: control group that received a clarithromycin-based triple regimen, and study group that received licorice in addition to the clarithromycin-based regimen for two weeks. H. pylori eradication was assessed six weeks after therapy. Data was analyzed by chi-square and t-test with SPSS 16 software.

Results:
Mean ages and SD were 38.8±10.9 and 40.1±10.4 for the study and control groups, respectively, statistically similar. Peptic ulcer was found in 30% of both groups. Response to treatment was 83.3% and 62.5% in the study and control groups, respectively. This difference was statistically significant.

Conclusion:
Addition of licorice to the triple clarithromycin-based regimen increases H. pylori eradication, especially in the presence of peptic ulcer disease.

Full text

BJID
632
1–5
Please
cite
this
article
in
press
as:
Aghamohammadi
AA,
et
al.
To
evaluate
of
the
effect
of
adding
licorice
to
the
standard
treatment
regimen
of
Helicobacter
pylori.
Braz
J
Infect
Dis.
2016.
http://dx.doi.org/10.1016/j.bjid.2016.07.015
ARTICLE IN PRESS
BJID
632
1–5
braz
j
infect
dis
2
0
1
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x(x
x):xxx–xxx
www.elsevier.com/locate/bjid
The
Brazilian
Journal
of
INFECTIOUS
DISEASES
Original
article
To
evaluate
of
the
effect
of
adding
licorice
to
the
standard
treatment
regimen
of
Helicobacter
pylori
Ali
Akbar
Haji
Aghamohammadia,
Ali
Zargara,
Sonia
Oveisib,
Rasoul
Samimia,
Q1
Sedigheh
Reisiana,∗
aDepartment
of
Internal
Medicine,
Velayat
Clinical
Research
Development
Unit,
Qazvin
University
of
Medical
Sciences,
Qazvin,
Iran
bMetabolic
Diseases
Research
Center,
Qazvin
University
of
Medical
Sciences,
Qazvin,
Iran
a
r
t
i
c
l
e
i
n
f
o
Article
history:
Received
14
March
2016
Accepted
29
July
2016
Available
online
xxx
Keywords:
Helicobacter
pylori
Licorice
Dyspepsia
Peptic
ulcer
a
b
s
t
r
a
c
t
Objective:
The
aim
of
this
study
was
to
evaluate
the
effect
of
licorice
in
H.
pylori
eradication
in
patients
suffering
from
dyspepsia
either
with
peptic
ulcer
disease
(PUD)
or
non-ulcer
dyspepsia
(NUD)
in
comparison
to
the
clarithromycin-based
standard
triple
regimen.
Methods:
In
this
randomized
controlled
clinical
trial,
120
patients
who
had
positive
rapid
urease
test
were
included
and
assigned
to
two
treatment
groups:
control
group
that
received
a
clarithromycin-based
triple
regimen,
and
study
group
that
received
licorice
in
addition
to
the
clarithromycin-based
regimen
for
two
weeks.
H.
pylori
eradication
was
assessed
six
weeks
after
therapy.
Data
was
analyzed
by
chi-square
and
t-test
with
SPSS
16
software.
Results:
Mean
ages
and
SD
were
38.8
±
10.9
and
40.1
±
10.4
for
the
study
and
control
groups,
respectively,
statistically
similar.
Peptic
ulcer
was
found
in
30%
of
both
groups.
Response
to
treatment
was
83.3%
and
62.5%
in
the
study
and
control
groups,
respectively.
This
difference
was
statistically
significant.
Conclusion:
Addition
of
licorice
to
the
triple
clarithromycin-based
regimen
increases
H.
pylori
eradication,
especially
in
the
presence
of
peptic
ulcer
disease.
©
2016
Sociedade
Brasileira
de
Infectologia.
Published
by
Elsevier
Editora
Ltda.
This
is
an
open
access
article
under
the
CC
BY-NC-ND
license
(http://creativecommons.org/licenses/
by-nc-nd/4.0/).
Introduction
Helicobacter
pylori
(H.
pylori)
is
a
Gram
negative
S
shaped
flag-
ellated
bacteria
infecting
half
of
mankind
with
a
very
variable
prevalence
depending
on
different
factors
such
as
race,
age,
and
socioeconomic
status
ranging
from
a
low
prevalence
in
developed
countries
to
a
prevalence
as
high
as
80%
in
devel-
oping
countries
like
Iran.1H.
pylori
is
a
successful
pathogen
∗Corresponding
author.
E-mail
address:
SRMDFM@gmail.com
(S.
Reisian).
which
can
persistently
survive
in
the
stomach
of
infected
persons
throughout
his/her
life
and
if
it
results
in
chronic
inflammation
serious
digestive
diseases
may
ensue
such
as
chronic
gastritis,
peptic
ulcer
disease
(PUD),
gastric
cancer,
and
gastric
MALT-oma
(mucosa
associated
lymphoid
tissue
lymphoma).2
Peptic
ulcer
disease
is
one
of
the
consequences
of
H.
pylori
infection
and
is
one
of
the
most
common
treatable
dis-
eases
worldwide.
The
commonest
cause
of
peptic
ulcer
is
H.
http://dx.doi.org/10.1016/j.bjid.2016.07.015
1413-8670/©
2016
Sociedade
Brasileira
de
Infectologia.
Published
by
Elsevier
Editora
Ltda.
This
is
an
open
access
article
under
the
CC
BY-NC-ND
license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
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BJID
632
1–5
Please
cite
this
article
in
press
as:
Aghamohammadi
AA,
et
al.
To
evaluate
of
the
effect
of
adding
licorice
to
the
standard
treatment
regimen
of
Helicobacter
pylori.
Braz
J
Infect
Dis.
2016.
http://dx.doi.org/10.1016/j.bjid.2016.07.015
ARTICLE IN PRESS
BJID
632
1–5
2
b
r
a
z
j
i
n
f
e
c
t
d
i
s
.
2
0
1
6;x
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x(x
x):xxx–xxx
pylori
and
if
not
eradicated
it
will
result
in
50–80%
relapse
in
6–12
months
after
treatment
interruption,3but
if
successfully
treated
its
recurrence
will
drop
to
6–20%,
as
reported
by
two
separate
meta-analyses.4,5
Relation
between
dyspepsia
and
H.
pylori
is
unclear,
but
eradication
leads
to
symptoms
improvement
in
7.1%
of
patients.6
American
College
of
Gastroenterology
(ACG)
recommends
the
treatment
of
H.
pylori
in
all
infected
patients
irrespective
of
the
presence
of
ulcer.
Recommended
first
line
standard
regimen
by
ACG
for
the
treating
H.
pylori
is
a
triple
regimen
containing
clarithromycin,
amoxicillin
or
metronidazole,
and
proton
pump
inhibitor
(PPI)
for
10–14
days.
Quadruple
regimen
is
recommended
in
areas
where
the
prevalence
and
resistance
to
clarithromycin
or
metronidazole
is
more
than
20%,
or
if
the
first
choice
has
been
tried
recently
or
repeatedly.7
Antibiotic
resistance
to
H.
pylori
has
increased
in
recent
past
years.
Compared
to
2010
the
resistance
rate
to
clar-
ithromycin
and
amoxicillin
in
2012
has
raised
significantly.8
The
effectiveness
of
the
present
therapeutic
regimen
is
still
not
satisfactory
and
despite
several
studies
the
best
treatment
regimen
for
treating
H.
pylori
remains
a
challenging
clinical
dilemma.9Antibiotic
resistance
and
adverse
effects
in
addi-
tion
to
poor
patient
compliance
have
limited
the
efficacy
of
H.
pylori
treatment.
Therefore,
the
role
of
herbal
medicine
has
been
evaluated
in
the
treatment
of
H.
pylori,
including
licorice
(liquorice).10
Licorice
herb
(Glycyrrhiza
glabra
-
G.
glabra)
has
routinely
been
used
for
centuries
in
traditional
Chinese.11 Roots
and
rhizomes
of
this
herb
has
been
reported
to
be
antioxidant,
antimicrobial,
and
antiviral.12,13 Furthermore,
G.
glabra
has
anti-inflammatory,
anticancer,
and
anti-ulcer
activity.14–16
Licorice
is
extracted
from
the
root
of
G.
glabra
herb
and
one
of
its
active
ingredient
is
glycyrrhizin
acid,
which
due
to
its
affinity
to
mineralocorticoid
receptors
may
result
in
edema
and
hypertension.
Therefore,
it
should
be
used
with
cau-
tion
in
patients
suffering
from
cardiovascular
disease
and/or
hypertension.17 (Fig.
1).
Fig.
1
–
Photograph
of
Glycyrrhiza
glabra
herb.
There
two
types
of
action
of
licorice
in
PUD
and
against
H.
pylori:
(1)
a
repairing
effect
in
PUD:
protective
mucosal
effect
by
secreting
a
material
named
as
secretin18;
and
(2)
antibacterial
and
anti-adhesive
effect
against
H.
pylori
by
inhibiting
DNA
gyrase
(a
crucial
enzyme
for
bacterial
replication
and
tran-
scription)
and
dihydrofolate
reductase
enzyme
blockage.19
In
addition,
the
polysaccharide
released
from
the
root
of
licorice
plays
an
inhibiting
role
in
H.
pylori
adhesion
to
gas-
tric
mucosa.20 Besides,
treatment
with
licorice
for
patients
suffering
from
dyspepsia
improves
their
clinical
complaints.21
Owing
to
the
rise
of
H.
pylori
resistance
against
antibiotics
and
the
effectiveness
of
licorice
for
treating
H.
pylori,
this
study
was
designed
to
compare
the
efficacy
of
adding
licorice
to
the
standard
clarithromycin-based
triple
regimen
in
the
treat-
ment
of
H.
pylori.
Material
and
methods
This
randomized
controlled
clinical
trial
was
conducted
in
Velayat
teaching
hospital
in
Qazvin
(northwest
of
Iran).
A
total
of
120
patients
over
16
years
of
age
referred
for
esophagogas-
troduodenoscopy
(EGD)
at
the
digestive
disease
outpatient
department
due
to
gastrointestinal
complains
entered
this
study
from
May
to
December
of
2015.
Biopsy
was
performed
when
indicated
by
the
endoscopist.
Patients
with
a
positive
rapid
urease
test
were
included
in
this
study
if
none
of
the
following
conditions
were
present:
pregnancy,
use
of
proton
pump
inhibitor
(PPI),
bismuth
or
antibiotic
in
the
past
two
weeks,
gastrointestinal
(GI)
bleed-
ing
or
any
complication
of
PUD,
giant
ulcer,
gastric
ulcer,
ethanol
consumption
or
substance
abuse,
chronic
underlying
disease
like
diabetes
mellitus,
hypertension,
cirrhosis,
cere-
brovascular
attack,
coronary
artery
disease,
and
gastric
cancer.
Patients
who
were
reluctant
to
continue
the
treatment
or
com-
plete
the
follow-up
or
suffering
from
a
comorbidity
needing
non-steroidal
anti-inflammatory
drugs
(NSAIDs)
or
antibiotic
to
be
continued
during
the
period
of
study
were
excluded.
Informed
consent
was
obtained
from
all
eligible.
Sixty
patients
were
randomly
assigned
to
receive
one
of
two
treatment
regi-
mens:
triple
regimen
consisting
of
clarithromycin
(500
mg
BID)
+
Amoxicillin
(1
gr
qd)
+
20
mg
BID
of
Omeprazole
(control
group)
or
the
same
regimen
supplemented
by
licorice
[D-Reglis
(380
mg
BID)
made
by
Iran
daruc
Pharmacy
Company]
for
two
weeks
(LR
group).
Both
groups
received
at
least
four
weeks
of
treatment
with
omeprazole
20
mg
daily
subsequently.
Two
weeks
after
completing
the
treatment,
H.
pylori
eradication
was
assessed
with
H.
pylori
stool
antigen
(HPSA)
test
by
Ag
ACON
Biotech
(Hang
Zhou)
Co.,
Ltd.
This
study
is
registered
at
Iran
Registration
Clinical
Trial
Center
and
was
approved
with
the
Irct
registration
number:
IRCT2014061718124N1.
The
outcome
of
this
study
was
H.
pylori
eradication.
Data
were
stored
at
SPSS
16
software
and
analyzed
by
using
of
t-test,
chi-square
test.
A
p-value
<0.05
was
considered
significant.
Results
Out
of
120
eligible
patients,
110
patients
completed
the
study
complying
with
the
prescribed
medications
and
follow-up;
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125

BJID
632
1–5
Please
cite
this
article
in
press
as:
Aghamohammadi
AA,
et
al.
To
evaluate
of
the
effect
of
adding
licorice
to
the
standard
treatment
regimen
of
Helicobacter
pylori.
Braz
J
Infect
Dis.
2016.
http://dx.doi.org/10.1016/j.bjid.2016.07.015
ARTICLE IN PRESS
BJID
632
1–5
b
r
a
z
j
i
n
f
e
c
t
d
i
s
.
2
0
1
6;x
x
x(x
x):xxx–xxx
3
H.pylori infected patients (n=120)
Random allocation
Clarithromycin based
Control group (n=60)
2 patients was lost follow up
56 patients came back for follow up
2 patients discontinued treatment
for side effects
56 patients completed treatment
course
Analysis
54 patients completed treatment
course
2 patients discontinued treatment
for side effects
4 patients was lost follow up
56 patients came back for follow up
Follow-up
LR group (n=60)
Licorice
Fig.
2
–
Study
flow
chart
(Control
Group:
Clarithromycin
+Amoxicillin
+
Omeprazole
regimen,
Licorice
(LR)
Group:
Licorice
+
Clarithromycin
+Amoxicillin
+
Omeprazole).
54
patients
were
assigned
to
the
licorice
group
(LR)
and
54
patients
to
the
control
group
(schematic
presentation
of
study
groups
is
illustrated
in
Fig.
2).
Demographic
variables
of
both
treatment
groups
were
sim-
ilar.
Mean
ages
were
38.8
and
40.1
years
for
the
LR
and
control
groups,
respectively
(p
=
0.56);
35
patients
(51.0%)
of
LR
group
and
33
persons
(48.1%)
of
the
control
group
were
female
(p
>
0.05).
Patients
in
two
groups
were
also
similar
regarding
to
their
clinical
characteristics
(initial
complaints
and
endoscopic
findings).
Frequency
distribution
of
their
clin-
ical
characteristics
is
shown
in
Table
1.
Table
1
–
Clinical
characteristics
of
licorice
(LR)
and
control
groups.
Group
Clinical
characteristics
LR
group
(N:60)
Control
group
(N:60)
p-Value
Symptoms
Abdominal
pain
37
(61.7%)
42(70%)
0.442
Early
satisfied
8(13.3%)
5(8.3%)
0.558
Bloating
12(20.0%)
15(25%)
0.662
Heart
burn
13(21.7%)
15(25%)
0.829
Nausea
2(3.3%)
4(6.7%)
0.679
Endoscopic
finding
Duodenal
ulcer
21(35.0%)
18(30.0%)
0.697
Antral
erythema
29(48.3%)
32(55.3%)
0.715
Antral
nodularity
7(11.7%)
5(8.3%)
0.762
Duodenal
erythema
4(6.7%)
2(3.3%)
0.679
No
pathologic
finding
7(11.7%)
8(13.3%)
1.000
Furthermore,
both
groups
had
similar
rates
of
endoscopic
diagnosis
of
PUD
or
non-ulcer
dyspepsia
(NUD):
21
(35%)
and
18
patients
(30%)
in
the
LR
and
control
groups,
respectively,
had
PUD
(Table
2).
HPSA
negative,
the
surrogate
for
H.
pylori
eradication
and
positive
therapeutic
response,
was
83.3%
in
the
LR
group
com-
pared
to
62.5%
in
the
control
group
(p
=
0.018).
Response
rate
based
on
endoscopic
findings
was
significantly
higher
for
the
LR
group
to
treat
PUD,
but
not
for
NUD
(Table
3).
Discussion
This
study
was
conducted
with
the
aim
of
evaluating
the
effectiveness
of
licorice
in
H.
pylori
eradication
of
patients
suf-
fering
from
dyspepsia
(both
PUD
and
NUD)
compared
to
the
clarithromycin-based
standard
triple
regimen.
Results
of
this
study
showed
that
adding
a
low
dose
licorice
(D-Reglis
380
mg
BID)
to
the
standard
triple
treatment
results
in
a
more
effective
H.
pylori
eradication,
especially
in
patients
with
PUD.
During
the
recent
past
decades
many
studies
on
H.
pylori
infection
have
been
conducted
to
define
the
adequate
therapy.
As
H.
pylori
is
considered
a
major
risk
factor
for
upper
digestive
problems
guidelines
often
recommend
treating
all
infected
persons
irrespective
of
the
clinical
presentation.
Besides
the
clinical
impact,
H.
pylori
eradication
would
also
prevent
its
spread.22
In
the
present
study
the
addition
of
licorice
increased
the
effectiveness
of
H.
pylori
eradication
compared
to
standard
clarithromycin-based
triple
regimen,
a
finding
similar
to
pre-
vious
in
vitro
studies.20,23
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163

BJID
632
1–5
Please
cite
this
article
in
press
as:
Aghamohammadi
AA,
et
al.
To
evaluate
of
the
effect
of
adding
licorice
to
the
standard
treatment
regimen
of
Helicobacter
pylori.
Braz
J
Infect
Dis.
2016.
http://dx.doi.org/10.1016/j.bjid.2016.07.015
ARTICLE IN PRESS
BJID
632
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x(x
x):xxx–xxx
Table
2
–
Endoscopic
diagnosis
of
licorice
(LR)
and
control
groups.
Endoscopic
diagnosis
Peptic
ulcer
Non-ulcer
dyspepsia
Total
p-Value
LR
group
(N:60)
21
(35.0%)
39
(65.0%)
60
(100.0%) 0.697
Control
group
(N:60)
18
(30%)
42
(70.0%)
60
(100.0%)
Total
39
(32.5%)
81
(67.5%)
120
(100.0%)
Table
3
–
Frequency
of
response
to
treatment
(negative
HPSA)
in
the
LR
and
control
groups.
aHPSA
Endoscopic
diagnosis
LR
group
(N:54)
Total
Control
group
(N:56)
Total
p-Value
Negative
N
(%)
Positive
N
(%)
N
(%)
Negative
N
(%)
Positive
N
(%)
N
(%)
Non-ulcer
dyspepsia
28
(82.4%)
6
(17.6%)
34
(100%)
27
(67.5%)
13
(32.5%)
40
(100%)
0.186
Peptic
ulcer
disease
17
(85.0%)
3
(15.0%)
20
(100%)
8
(50%)
8
(50%)
16
(100%)
0.034*
Total
45
(83.3%)
9
(16.7%)
54
(100%)
35
(62.5%)
21
(37.5%)
56
(100%)
0.018*
aHelicobacter
pylori
stool
antigen.
∗Significant
level
was
>0.05.
Toshio
Fukai
investigated
the
anti-H.
pylori
in
vitro
effect
of
various
preparations
of
licorice
and
showed
that
the
leaves
and
rhizomes
of
this
herb
prevented
the
multiplication
of
H.
pylori.
In
addition,
he
also
proved
that
licorice
had
anti-H.
pylori
effect
against
the
species
resistant
to
clarithromycin.24
Asha
MK
reported
that
G.
glabra
has
antimicrobial
effect
against
several
Gram
positive
and
Gram
negative
bacteria
including
H.
pylori.
Additionally,
licorice
is
also
beneficial
against
H.
pylori
due
to
its
anti-adhesive
property.25
Dosage
of
licorice
has
varied
in
few
clinical
studies,
such
as
in
a
study
by
Sreenivasulu
Parum
et
al.
in
which
a
dose
of
120
mg/day
was
used
for
H.
pylori
eradication
in
patients
with
dyspepsia,21 or
a
dose
of
250
mg
TID
in
PUD
with
H.
pylori
infection
in
a
study
by
Rahnama
et
al.,26 or
a
tablet
of
D-Reglis
380
mg
BID
in
a
study
by
Momeni
et
al.27
Rahnama
et
al.
compared
the
effectiveness
of
quadruple
treatment
including
licorice
to
the
same
regimen
using
bis-
muth
in
substitution
of
licorice
in
patients
with
PUD.
The
eradication
rates
were
45%
and
75%
with
licorice
and
bismuth,
respectively,
showing
higher
effectiveness
with
the
regimen
including
licorice.26 Momeni
et
al.
compared
the
same
two
quadruple
regimens
and
showed
similar
eradication
rates
and
concluded
that
D-Reglis
can
be
a
substitute
for
bismuth
in
quadruple
regimen.27
In
patients
with
PUD
our
results
showed
significantly
higher
eradication
rate
of
H.
pylori
in
the
LR
group
compared
with
the
control
group
(p
=
0.03),
in
line
with
the
report
by
Rah-
nama
et
al.
However,
the
eradication
rate
with
licorice
was
not
different
from
the
control
group
in
patients
with
dys-
pepsia
(p
=
0.18),
as
found
by
Momeni
et
al.
The
discrepancy
between
the
results
reported
by
Rahnama
et
al.
and
Momeni
et
al.
is
due
to
the
of
patients
studied.
Rahnama
et
al.
eval-
uated
the
H.
pylori
eradication
in
patients
with
PUD
whereas
the
study
by
Momeni
et
al.
entered
patients
with
both
PUD
and
NUD.
Another
debatable
issue
regarding
the
effect
of
licorice
on
H.
pylori
eradication
is
the
duration
of
treatment
for
improving
patients’
symptoms
of
dyspepsia.
In
a
clinical
study
Raveendra
et
al.
evaluated
the
effect
of
licorice
against
placebo
in
func-
tional
dyspepsia
and
found
that
those
who
received
licorice
for
one
month
had
a
lower
Nepean
Dyspepsia
Index
and
therefore
showed
better
improvement
of
symptoms
compared
to
those
who
received
placebo.28
In
a
study
by
Sreenivasulu
Puram
et
al.
patients
suffering
for
dyspepsia
with
H.
pylori
infection
were
prescribed
licorice
at
a
dose
of
120
mg
a
day
for
60
days.
The
response
rate
was
compared
against
the
placebo
using
the
HPSA
test
on
days
30
and
60;
showing
that
HPSA
test
on
day
60
was
negative
in
56%
of
licorice
group
against
4%
with
placebo
denoting
a
statistically
significant
difference.21
Based
on
above
two
studies
it
seems
that
licorice
in
dyspep-
sia,
besides
its
antimicrobial
nature
in
H.
pylori
infection,
has
also
anti-inflammatory
effect.
Therefore,
generally
speaking
prescribing
licorice
for
H.
pylori
eradication
at
a
higher
dose,
and
longer
duration
should
also
be
considered.
Conclusion
Because
of
the
unsatisfactory
rate
of
H.
pylori
eradication
by
the
standard
triple
regimen,
especially
in
areas
with
high
resis-
tance
rates
to
clarithromycin
and
amoxicillin,
adding
licorice
to
the
triple
regimen
significantly
increase
H.
pylori
eradication
in
patients
with
PUD.
Finally,
it
is
recommended
to
use
licorice
in
addition
to
the
triple
regimen
as
first
line
treatment
in
order
to
decrease
drug
adverse
effects
and
its
cost,
and
to
increase
patient
compli-
ance.
Authors’
contribution
i)
Substantial
contributions
to
the
conception
or
design
of
the
work;
or
the
acquisition,
analysis,
or
interpretation
of
data
for
the
work:
Ali
Akbar
Hajiaghamohammadi,
Sedigheh
Reisian,
Sonia
Oveisi,
RasoulSamimi.
ii)
Drafting
the
work
or
revising
it
critically
for
impor-
tant
intellectual
content:
Ali
Akbar
Hajiaghamohammadi,
Sedigheh
Reisian,
Sonia
Oveisi,
Ali
Zargar.
iii)
Final
approval
of
the
version
to
be
published;
Ali
Akbar
Hajiaghamohammadi,
Sedigheh
Reisian,
Sonia
Oveisi,
Ali
Zargar
and
Agreement
to
be
accountable
for
all
aspects
of
the
work
in
ensuring
that
questions
related
to
the
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Please
cite
this
article
in
press
as:
Aghamohammadi
AA,
et
al.
To
evaluate
of
the
effect
of
adding
licorice
to
the
standard
treatment
regimen
of
Helicobacter
pylori.
Braz
J
Infect
Dis.
2016.
http://dx.doi.org/10.1016/j.bjid.2016.07.015
ARTICLE IN PRESS
BJID
632
1–5
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i
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i
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1
6;x
x
x(x
x):xxx–xxx
5
accuracy
or
integrity
of
any
part
of
the
work
are
appropriately
investigated
and
resolved;
Ali
Akbar
Haji-
aghamohammadi,
Sedigheh
Reisian,
Sonia
Oveisi.
Conflicts
of
interest
There
is
no
conflict
of
interest.
Acknowledgements
Authors
of
this
article
are
thankful
for
the
valuable
cordial
and
dedicated
cooperation
of
staffs
in
Clinical
Research
Develop-
ment
Unit
of
Velayat
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