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Supplementary Table 1. Study characteristics: An overview of studies regarding APRI for prediction of varices in liver cirrhosis.
First
author
(Year)
RegionsStudy
description
No.
total
Pts
Age (year)Male
(%)
Etiology of
cirrhosis
HCC
(%)
Child-Pugh
class (%)
No. Pts
who
underwent
endoscopy
Location
of
varices
Prevalenc
e of
varices
(%)
Prevalence
of large
varices (%)
Definitions of large
varices
Cut-off
of
varices/
large
varices
QUADAS
Score
Morishita
(2014)Japan NA 92 68.7±9.3 51.1% HCV 100% 50.0%
A 65.2 %
B 32.6 %
C 2.2 %
92 EV 51.1% 33.7%
Straight small-
calibered varices with
red color signs;
moderately enlarged,
beady varices;
markedly enlarged,
nodular, or tumor-
shaped varices.
1.5 /
1.6210
Salzl
(2014)Austria Prospective 88 NA NA
Viral 32%,
alcohol 49%,
viral+alcohol
7%,
cryptogenic or
others 12%
NA
A 17%
B 66%
C 17%
88 EV 69.3% 39.8% NA1.906 /
NA8
Calvaruso
(2013)Italy Prospective 96 63.2±9.5 69.8% HCV 100% 0.0% A 100% 96 EV 56.3% 27.1%
>30% of the lumen
was occupied.
1.5 /
210
Feng
(2013)China Prospective 89
55.04±11.1
178.7%
HBV 71.9%,
HCV 3.4%,
alcohol 7.9%,
cryptogenic or
others 16.9%
0.0% NA 89 EV/GV 66.3% 30.3%
Tortuous varices with
red color signs; beady,
nodular, or tumor-
shaped varices with or
without red color signs.
0.93 /
1.0211
Zambam
de Mattos
(2013)
BrazilRetrospective
cross-sectional164 56.7 59.8%
HCV 54.88%,
alcohol 38.41%,
others 6.7%
NA
A 52.44%
B/C
47.56%
164 EV 72.6% NA NA1.3 /
NA8
Pai
(2012)India
Prospective
(abstract)114 NA NA NA NA NA 114 EV NA 48.2% NA
NA /
150.568
Wang
(2012)China Prospective 126 54.5±10.1 73.8% HBV 100% 0.0% A 100% 126 EV 38.1% 10.3%
Small varices of red
color, and medium or
large varices.
0.77 /
1.2410
Reed
(2011)England NA (abstract) 96 NA NA
HCV 28.1%,
alcohol 27.1%,
cryptogenic or
others 44.8%
NA NA 96 EV 26.0% 13.5% NANA /
NA8
Stefanesc
u
(2011)
Romania Cross-sectional 23155.6
6±9.51958.4%
HCV 49.78%,
alcohol 38.96%,
viral+alcohol
11.26%
NA
A 75.9%
B 18.4%
C 5.7%
231 EV 68.0% 29.5%
Enlarged, tortuous EV
occupying <1/3 of the
lumen; large, coil-
shaped EV occupying
>1/3 of the lumen.
1.434 /
2.20110
Tafarel
(2011)Brazil Prospective 300 53.1±12.15 64.3%
Viral 49%,
alcohol 24%,
viral+alcohol
5.33%,
cryptogenic or
others 21.67%
0.0%
A 70.7%
B 24.3%
C 5%
300 EV 57.0% 3.3%
Varices did not
disappear with air
insufflation and
occupied >1/3 of the
esophageal lumen.
1.64 /
NA10
Sebastiani
(2010)Italy Retrospective 510 59.5±11 58.0%
HBV 8.8%,
HCV 55.1%,
alcohol 30.4%,
0.0%
A 79.4%
B 16.7%
C 3.9%
510 EV 56.9% 19.0%
Non-confluent EV
protruding in the lumen
despite insufflation;
1.4 /
1.512
cryptogenic or
others 5.7%
confluent thick EV,
gastroesophageal
junction varices and
isolated GVs.
Castéra
(2009)France Prospective 70 54.1±11.8 60.0% HCV 100% NA A 100% 70 EV 35.7% 18.6% NA
1.3 /
1.39
Abbreviations: EV,esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.
Supplementary Table 2. Study quality: An overview of studies regarding APRI for prediction of varices in liver cirrhosis.
No. ItemSalz
l Calvaruso
Zambam de
MattosMorishita Wang Tafarel Stefanescu Sebastiani Castéra Pai
Ree
d Feng
1Was the spectrum of patients representative of the patients
who will receive the test in practice?Y N U N N N N Y N U Y Y
2 Were selection criteria clearly described? Y Y N Y Y Y Y Y Y N U Y
3Is the reference standard likely to correctly classify the target
condition?Y Y Y Y Y Y Y Y Y Y Y Y
4
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition
did not change between the two tests? (≤3 months)
U Y N U U Y U Y U Y U U
5Did the whole sample or a random selection of the sample,
receive verification using a reference standard of diagnosis?Y Y Y Y Y Y Y Y Y Y Y Y
6Did patients receive the same reference standard regardless
of the index test result?Y Y Y Y Y Y Y Y Y Y Y Y
7
Was the reference standard independent of the index test
(i.e. the index test did not form part of the reference
standard)?
Y Y Y Y Y Y Y Y Y Y Y Y
8Was the execution of the index test described in sufficient
detail to permit replication of the test?Y N Y Y Y N Y Y Y N N Y
9Was the execution of the reference standard described in
sufficient detail to permit its replication?N Y N Y Y Y Y Y N N N Y
10Were the index test results interpreted without knowledge of
the results of the reference standard?U U U U U U U U U U U U
11Were the reference standard results interpreted without
knowledge of the results of the index test?U U U U U U U U U U U U
12
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
Y Y Y Y Y Y Y Y Y Y Y Y
13 Were uninterpretable/ intermediate test results reported? U Y Y Y Y Y Y Y Y Y Y Y
14 Were withdrawals from the study explained? N Y Y Y Y Y Y Y Y Y Y Y
Score 8 10 8 10 10 10 10 12 9 8 8 11
Supplementary Table 3. An overview of studies regarding AAR for prediction of varices in liver cirrhosis.
First
author
(Year)
RegionsStudy
description
No.
total
Pts
Age
(year)
Male
(%)
Etiology of
cirrhosis
HCC
(%)
Child-Pugh
class (%)
No. Pts
who
underwent
endoscopy
Locatio
n of
varices
Prevalence
of varices
(%)
Prevalence
of large
varices (%)
Definitions of large
varices
Cut-off of
varices/
large
varices
QUADAS
Score
Calvaruso
(2013)Italy Prospective 96 63.2±9.5 69.8% HCV 100% 0.0% A 100% 96 EV 56.3% 27.1%
>30% of the lumen
was occupied.0.8/ 1 10
Reed
(2011)England NA (abstract) 96 NA NA
HCV 28.1%,
alcohol 27.1%,
cryptogenic or
others 44.8%
NA NA 96 EV 26.0% 13.5% NA NA 8
Sebastiani
(2010)Italy
Retrospectiv
e510 59.5±11 58.0%
HBV 8.8%,
HCV 55.1%,
alcohol 30.4%,
cryptogenic or
others 5.7%
0.0%
A 79.4%
B 16.7%
C 3.9%
510 EV 56.9% 19.0%
Non-confluent EV
protruding in the
lumen despite
insufflation; confluent
thick EV,
gastroesophageal
junction varices and
isolated GVs.
1/ 1.1 12
Castéra
(2009)France Prospective 70 54.1±11.8 60.0% HCV 100% NA A 100% 70 EV 35.7% 18.6% NA 1/ 1 9
Abbreviations: EV, esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.
Supplementary Table 4. Study quality: An overview of studies regarding AAR for prediction of varices in liver
cirrhosis.
No
.Item Calvaruso Sebastiani Castéra Reed
1Was the spectrum of patients representative of the patients
who will receive the test in practice?N Y N Y
2 Were selection criteria clearly described? Y Y Y U
3Is the reference standard likely to correctly classify the target
condition?Y Y Y Y
4
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition
did not change between the two tests? (≤3 months)
Y Y U U
5Did the whole sample or a random selection of the sample,
receive verification using a reference standard of diagnosis?Y Y Y Y
6Did patients receive the same reference standard regardless
of the index test result?Y Y Y Y
7Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?Y Y Y Y
8Was the execution of the index test described in sufficient
detail to permit replication of the test?N Y Y N
9Was the execution of the reference standard described in
sufficient detail to permit its replication?Y Y N N
10Were the index test results interpreted without knowledge of
the results of the reference standard?U U U U
11Were the reference standard results interpreted without
knowledge of the results of the index test?U U U U
12
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
Y Y Y Y
13 Were uninterpretable/ intermediate test results reported? Y Y Y Y
14 Were withdrawals from the study explained? Y Y Y Y
Score 10 12 9 8
Supplementary Table 5. Study characteristics: An overview of studies regarding FIB-4 for prediction of varices in liver cirrhosis.
First
author
(Year)
RegionsStudy
description
No.
total
Pts
Age
(year)
Male
(%)
Etiology of
cirrhosis
HCC
(%)
Child-Pugh
class (%)
No. Pts
who
underwent
endoscopy
Location
of
varices
Prevalence
of varices
(%)
Prevalenc
e of large
varices
(%)
Definitions of
large varices
Cut-off
of
varices/
large
varices
QUADAS
Score
Morishita
(2014)Japan NA 92 68.7±9.3 51.1% HCV 100% 50.0%
A 65.2 %
B 32.6 %
C 2.2 %
92 EV 51.1% 33.7%
Straight small-
calibered varices
with RC signs;
moderately
enlarged, beady
varices; markedly
enlarged, nodular,
or tumor-shaped
varices.
6.21/
7.710
Reed
(2011)England NA (abstract) 96 NA NA
HCV 28.1%,
alcohol 27.1%,
cryptogenic or
others 44.8%
NA NA 96 EV 26.0% 13.5% NANA/
NA7
Stefanesc
u
(2011)
Romania Cross-
sectional
231 55.6
6±9.519
58.4% HCV 49.78%,
alcohol 38.96%,
viral+alcohol
11.26%
NA A 75.9%
B 18.4%
C 5.7%
231 EV 68.0% 29.5% Enlarged, tortuous
EV occupying less
than one third of
the lumen; large,
coil-shaped EV
occupying more
than one third of
3.98/
6.7498
10
the lumen.
Sebastiani
(2010)Italy Retrospective 510 59.5±11 58.0%
HBV 8.8%,
HCV 55.1%,
alcohol 30.4%,
cryptogenic or
others 5.7%
0.0%
A 79.4%
B 16.7%
C 3.9%
510 EV 56.9% 19.0%
Non-confluent EV
protruding in the
lumen despite
insufflation;
confluent thick EV,
gastroesophageal
junction varices
and isolated
gastric varices.
3.5/
4.312
Hassan
(2014)Egypt Prospective 65
52.40 ±
6.1560.0% HCV 100% 0.0%
A 80.0%
B 20.0%65 EV 76.9% 49.2%
Enlarged, tortuous
EV occupying less
than one-third of
the lumen; large,
coil-shaped EV
occupying more
than one-third of
the lumen.
2.8/
3.310
Abbreviations: EV, esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.
Supplementary Table 6. Study quality: An overview of studies regarding FIB-4 for prediction of varices in liver cirrhosis.
No. Item Morishita Stefanescu Sebastiani Reed Hassan
1Was the spectrum of patients representative of the patients
who will receive the test in practice?N N Y Y N
2 Were selection criteria clearly described? Y Y Y U Y
3Is the reference standard likely to correctly classify the target
condition?Y Y Y Y Y
4
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition
did not change between the two tests? (≤3 months)
U U Y U U
5Did the whole sample or a random selection of the sample,
receive verification using a reference standard of diagnosis?Y Y Y Y Y
6Did patients receive the same reference standard regardless
of the index test result?Y Y Y Y Y
7Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?Y Y Y Y Y
8Was the execution of the index test described in sufficient
detail to permit replication of the test?Y Y Y N Y
9Was the execution of the reference standard described in
sufficient detail to permit its replication?Y Y Y N Y
10Were the index test results interpreted without knowledge of
the results of the reference standard?U U U U U
11Were the reference standard results interpreted without
knowledge of the results of the index test?U U U U U
12Were the same clinical data available when test results were
interpreted as would be available when the test is used in Y Y Y U Y
practice?
13 Were uninterpretable/ intermediate test results reported? Y Y Y Y Y
14 Were withdrawals from the study explained? Y Y Y Y Y
Score 10 10 12 7 10
Supplementary Table 7. Study characteristics: An overview of studies regarding Lok for prediction of varices in liver cirrhosis.
First
author
(Year)
RegionsStudy
description
No.
total
Pts
Age
(year)
Male
(%)
Etiology of
cirrhosis
HCC
(%)
Child-Pugh
class (%)
No. Pts
who
underwent
endoscopy
Location
of
varices
Prevalence
of varices
(%)
Prevalence
of large
varices (%)
Definitions of large
varices
Cut-off
of
varices/
large
varices
QUADAS
Score
Hassan
(2014)Egypt Prospective 65
52.40 ±
6.1560.0% HCV 100%
0.0
%
A 80.0%
B 20.0%65 EV 76.9% 49.2%
Enlarged, tortuous EV
occupying <1/3 of the
lumen; large, coil-
shaped EV occupying
>1/3 of the lumen.
0.63/
0.710
Stefanescu
(2011)
Romania Cross-sectional 23155.6
6±9.51958.4%
HCV 49.78%,
alcohol
38.96%,
viral+alcohol
11.26%
NA
A 75.9%
B 18.4%
C 5.7%
231 EV 68.0% 29.5%
Enlarged, tortuous EV
occupying <1/3 of the
lumen; large, coil-
shaped EV occupying
>1/3 of the lumen.
0.62/
0.79610
Sebastiani
(2010)Italy Retrospective 510 59.5±11 58.0%
HBV 8.8%,
HCV 55.1%,
alcohol 30.4%,
cryptogenic or
others 5.7%
0.0
%
A 79.4%
B 16.7%
C 3.9%
510 EV 56.9% 19.0%
Non-confluent EV
protruding in the lumen
despite insufflation;
confluent thick EV,
gastroesophageal
junction varices and
isolated GVs.
0.9/
1.512
Castéra
(2009)France Prospective 70 54.1±11.8 60.0% HCV 100% NA A 100% 70 EV 35.7% 18.6% NA
0.6/
0.69
Abbreviations: EV,esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.
Supplementary Table 8. Study quality: An overview of studies regarding Lok for prediction of varices in liver
cirrhosis.
No
.Item Stefanescu Sebastiani Hassan Castéra
1Was the spectrum of patients representative of the
patients who will receive the test in practice?N Y N N
2 Were selection criteria clearly described? Y Y Y Y
3Is the reference standard likely to correctly classify the
target condition?Y Y Y Y
4
Is the time period between reference standard and index
test short enough to be reasonably sure that the target
condition did not change between the two tests? (≤3
months)
U Y U U
5
Did the whole sample or a random selection of the sample,
receive verification using a reference standard of
diagnosis?
Y Y Y Y
6Did patients receive the same reference standard
regardless of the index test result?Y Y Y Y
7
Was the reference standard independent of the index test
(i.e. the index test did not form part of the reference
standard)?
Y Y Y Y
8Was the execution of the index test described in sufficient
detail to permit replication of the test?Y Y Y Y
9Was the execution of the reference standard described in
sufficient detail to permit its replication?Y Y Y N
10 Were the index test results interpreted without knowledge U U U U
of the results of the reference standard?
11Were the reference standard results interpreted without
knowledge of the results of the index test?U U U U
12
Were the same clinical data available when test results
were interpreted as would be available when the test is
used in practice?
Y Y Y Y
13 Were uninterpretable/ intermediate test results reported? Y Y Y Y
14 Were withdrawals from the study explained? Y Y Y Y
Score 10 12 10 9
Supplementary Table 9. Study characteristics: An overview of studies regarding Forns score for prediction of varices in liver cirrhosis.
First
author
(Year)
RegionsStudy
description
No.
total
Pts
Age
(year)
Male
(%)
Etiology of
cirrhosis
HCC
(%)
Child-Pugh
class (%)
No. Pts
who
underwent
endoscopy
Locatio
n of
varices
Prevalence
of varices
(%)
Prevalence
of large
varices (%)
Definitions of large
varices
Cut-off
of
varices/
large
varices
QUADAS
Score
Hassan
(2014)Egypt Prospective 65
52.40 ±
6.1560.0% HCV 100% 0.0%
A 80.0%
B 20.0%65 EV 76.9% 49.2%
Enlarged, tortuous EV
occupying <1/3 of the
lumen; large, coil-shaped
EV occupying >1/3 of the
lumen.
6.61/
6.910
Stefanesc
u
(2011)
Romania Cross-sectional 231
55.6
6±9.51
9
58.4%
HCV 49.78%,
alcohol 38.96%,
viral+alcohol
11.26%
NA
A 75.9%
B 18.4%
C 5.7%
231 EV 68.0% 29.5%
Enlarged, tortuous EV
occupying <1/3 of the
lumen; large, coil-shaped
EV occupying >1/3 of the
lumen.
7.297/
8.53810
Sebastiani
(2010)Italy Retrospective 510
59.5±1
158.0%
HBV 8.8%,
HCV 55.1%,
alcohol 30.4%,
cryptogenic or
others 5.7%
0.0%
A 79.4%
B 16.7%
C 3.9%
510 EV 56.9% 19.0%
Non-confluent EV
protruding in the lumen
despite insufflation;
confluent thick EV,
gastroesophageal
junction varices and
isolated GVs.
8.5/
8.812
Abbreviations: EV, esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.
Supplementary Table 10. Study quality: An overview of studies regarding Forns score for prediction of
varices in liver cirrhosis.
No. Item Stefanescu Sebastiani Hassan
1Was the spectrum of patients representative of the patients
who will receive the test in practice?N Y N
2 Were selection criteria clearly described? Y Y Y
3Is the reference standard likely to correctly classify the target
condition?Y Y Y
4
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition
did not change between the two tests? (≤3 months)
U Y U
5Did the whole sample or a random selection of the sample,
receive verification using a reference standard of diagnosis?Y Y Y
6Did patients receive the same reference standard regardless
of the index test result?Y Y Y
7Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?Y Y Y
8Was the execution of the index test described in sufficient
detail to permit replication of the test?Y Y Y
9Was the execution of the reference standard described in
sufficient detail to permit its replication?Y Y Y
10Were the index test results interpreted without knowledge of
the results of the reference standard?U U U
11Were the reference standard results interpreted without
knowledge of the results of the index test?U U U
12 Were the same clinical data available when test results were Y Y Y
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/intermediate test results reported? Y Y Y
14 Were withdrawals from the study explained? Y Y Y
Score 10 12 10
Supplementary Table 11. Study characteristics: An overview of studies regarding FibroIndex for prediction of varices in liver cirrhosis.
First
author
(Year)
RegionsStudy
description
No.
total
Pts
Age
(year)
Male
(%)
Etiology of
cirrhosis
HCC
(%)
Child-Pugh
class (%)
No. Pts
who
underwent
endoscopy
Location
of
varices
Prevalence
of varices
(%)
Prevalence
of large
varices (%)
Definitions of large
varices
Cut-off of
varices/
large
varices
QUADAS
Score
Sebastiani
(2010)
ItalyRetrospectiv
e510 59.5±11 58.0%
HBV 8.8%,
HCV 55.1%,
alcohol 30.4%,
cryptogenic or
others 5.7%
0.0%
A 79.4%
B 16.7%
C 3.9%
510 EV 56.9% 19.0%
Non-confluent EV
protruding in the lumen
despite insufflation;
confluent thick EV,
gastroesophageal junction
varices and isolated GVs.
2.2/
2.512
Abbreviations: EV, esophageal varices; GV, gastric varices; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.
Supplementary Table 12. Study quality: An overview of studies regarding
FibroIndex for prediction of varices in liver cirrhosis.
No. Item Sebastiani
1Was the spectrum of patients representative of the patients
who will receive the test in practice?Y
2 Were selection criteria clearly described? Y
3Is the reference standard likely to correctly classify the target
condition?Y
4
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition
did not change between the two tests? (≤3 months)
Y
5Did the whole sample or a random selection of the sample,
receive verification using a reference standard of diagnosis?Y
6Did patients receive the same reference standard regardless
of the index test result?Y
7Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?Y
8Was the execution of the index test described in sufficient
detail to permit replication of the test?Y
9Was the execution of the reference standard described in
sufficient detail to permit its replication?Y
10Were the index test results interpreted without knowledge of
the results of the reference standard?U
11Were the reference standard results interpreted without
knowledge of the results of the index test?U
12 Were the same clinical data available when test results were Y
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? Y
14 Were withdrawals from the study explained? Y
Score 12
Supplementary Figure 1. Flowchart of study inclusion regarding APRI score.
Supplementary Figure 2. Flowchart of study inclusion regarding
AAR score.
Supplementary Figure 3. Flowchart of study inclusion regarding
FIB-4 score.
Supplementary Figure 4. Flowchart of study inclusion
regarding FI score.
Supplementary Figure 5. Flowchart
of study inclusion regarding King score.
Supplementary Figure 6. Flowchart
of study inclusion regarding Lok score.
Supplementary Figure 7. Flowchart of study inclusion
regarding Forns score.
Supplementary Figure 8. Flowchart of study inclusion
regarding FibroIndex score.
Supplementary Figure 9. Summary PLRs of APRI, AAR,
and Lok scores for the prediction of varices in liver cirrhosis. Panel A: APRI; panel B: AAR; panel C: Lok.
Supplementary Figure 10. Summary PLRs of APRI, AAR, FIB-4, Lok, and Forns scores for
the prediction of large varices in liver cirrhosis. Panel A: APRI; panel B: AAR; panel C: FIB-4; panel D: Lok; panel E: Forns.
Supplementary Figure 11. Summary NLRs of APRI, AAR, and Lok scores for the prediction of varices in liver cirrhosis.
Panel A: APRI; panel B: AAR; panel C: Lok.
Supplementary Figure 12. Summary NLRs of APRI, AAR, FIB-4, Lok, and Forns scores for
the prediction of large varices in liver cirrhosis. Panel A: APRI; panel B: AAR; panel C: FIB-4; panel D: Lok; panel E: Forns.
Supplementary Figure 13. Summary DORs of APRI, AAR, and Lok scores for the prediction of varices in liver
cirrhosis. Panel A: APRI; panel B: AAR; panel C: Lok.
Supplementary Figure 14. Summary DORs of APRI, AAR, FIB-4, Lok, and Forns scores
for the prediction of large varices in liver cirrhosis. Panel A: APRI; panel B: AAR; panel C: FIB-4; panel D: Lok; panel E: Forns.